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Sample records for repeated intravenous administration

  1. Safety of Ketoprofen in Cow calves following repeated intravenous administration

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    R. D. Singh

    2009-06-01

    Full Text Available Ketoprofen is a non steroidal anti-inflammatory drug (NSAID used for its anti-inflammatory,analgesic and antipyretic properties in Veterinary Medicine. The present study was planned to assess safety of ketoprofen (3 mg.kg-1 after repeated intravenous administration at 24 hours interval for five days in six crossbred cow calves (6-12 months age and weighing between 60-122 kg. Ketoprofen in calves was found safe based on evaluation of haematological (Hb, PCV, TLC and DLC, blood biochemical (AKP, ACP, AST, ALT, LDH, Total bilirubin, Serum Creatinine, BUN, Serum total protein, Serum albumin and Blood glucose parameters. [Vet. World 2009; 2(3.000: 105-107

  2. Pharmacokinetics of marbofloxacin after single intravenous and repeat oral administration to cats.

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    Albarellos, G A; Montoya, L; Landoni, M F

    2005-09-01

    The pharmacokinetic properties of marbofloxacin, a third generation fluoroquinolone, were investigated in six cats after single intravenous (IV) and repeat oral (PO) administration at a daily dose of 2 mg/kg. Marbofloxacin serum concentration was analysed by microbiological assay using Klebsiella pneumoniae ATCC 10031 as micro-organism test. Serum marbofloxacin disposition was best described by bicompartmental and mono-compartmental open models with first-order elimination after IV and oral dosing respectively. After IV administration, distribution was rapid (T(1/2(d)) 0.23+/-0.24 h) and wide, as reflected by the steady-state volume of distribution of 1.01+/-0.15 L/kg. Elimination from the body was slow with a body clearance of 0.09+/-0.02 L/h kg and a T(1/2) of 7.98+/-0.57 h. After repeat oral administration, absorption half-life was 0.86+/-1.59 h and T(max) of 1.94+/-2.11 h. Bioavailability was almost complete (99+/-29%) with a peak plasma concentration at the steady-state of 1.97+/-0.61 mug/mL. Drug accumulation was not significant after six oral administrations. Calculation of efficacy predictors showed that marbofloxacin has good therapeutic profile against Gram-negative and Gram-positive bacteria with a MIC(50) value <0.25 microg/mL.

  3. The effects of repeated intravenous iohexol administration on renal function in healthy beagles – a preliminary report

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    Kirberger Robert M

    2012-08-01

    Full Text Available Abstract Background Contrast induced nephrotoxicity (CIN is a well described syndrome in humans undergoing contrast medium examinations. To date CIN has received minimal attention in the veterinary literature despite increasing use of contrast medium examinations in computed tomographic studies. Methods This prospective study evaluated the effect of 1290 mg/kg iohexol given intravenously to 5 normal beagle dogs in a divided dose at an interval of 6–8 weeks. Renal function was evaluated by means of scintigraphically determined glomerular filtration rate (GFR and a variety of laboratory assays. Results Only GFR showed a significant decrease (17% after the second injection but not to a clinically or pathologically significant level. Conclusions No clinically significant effect of repeated contrast medium administration was determined in this limited study. However in dogs with reduced renal function the risk of CIN is likely to increase dramatically post contrast administration.

  4. Repeated intravenous administrations of teneurin-C terminal associated peptide (TCAP)-1 attenuates reinstatement of cocaine seeking by corticotropin-releasing factor (CRF) in rats.

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    Erb, Suzanne; McPhee, Matthew; Brown, Zenya J; Kupferschmidt, David A; Song, Lifang; Lovejoy, David A

    2014-08-01

    The teneurin c-terminal associated peptides (TCAP) have been implicated in the regulation of the stress response, possibly via a corticotropin-releasing factor (CRF)-related mechanism. We have previously shown that repeated intracerebroventricular (ICV) injections of TCAP-1 attenuate the reinstatement of cocaine seeking by CRF in rats. Here, we determined whether intravenous (IV) administrations of TCAP-1 would likewise attenuate CRF-induced reinstatement, and whether this effect would vary depending on the rat's history of cocaine self administration. Rats were trained to self-administer cocaine for 10 days, during once daily sessions that were either 3h ("short access"; ShA) or 6h ("long access"; LgA). Rats were then given five daily injections of TCAP-1 (0, 300, or 3,000 pmol, IV) in their home cage. Subsequently, they were returned to the self-administration chambers where extinction of cocaine seeking and testing for CRF-induced reinstatement of cocaine seeking was carried out. Repeated IV administrations of TCAP-1 were efficacious in attenuating CRF-induced reinstatement of cocaine seeking, but at different doses in ShA and LgA rats. Taken together, the findings extend previous work showing a consistent effect of repeated ICV TCAP-1 on CRF-induced reinstatement of cocaine seeking, and point to a potential therapeutic benefit of TCAP-1 in attenuating cocaine seeking behaviors.

  5. MR-angiography with intravenous administration of Gd-DTPA

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    Saito, Yoko; Yodono, Hiraku; Tarusawa, Koji; Sasaki, Taisuke; Akimura, Rumiko; Kanehira, Jiro; Takahashi, Satoshi; Takekawa, S.D.

    1989-05-01

    We carried out phase contrast MR-angiography of the lower extremities with intravenous administration of Gd-DTPA. Five healthy male volunteers, 25 to 40 years of age, were examined with a 0.5T MRI unit. We used fast scan (gradient echo) technique and it took about 8 minutes for whole procedure. Images were obtained before and after intravenous injection of Gd-DTPA. Injection dose was 0.1 mmol/kg. In two cases, we got images with variable flip angles. However angles of 30 or 40 degrees were thought to be best on the scan with Gd-DTPA. In three cases, we repeated short time procedures for about 4 minutes each time and continued to check the signal intensities of vessels for as long as one hour. The signal intensities greatly increased soon after administration of Gd-DTPA, and then they gradually decreased, but for as long as 60 minutes after administration they remained much higher than those before administration of Gd-DTPA. MR-angiography with Gd-DTPA was found very useful to demonstrate the peripheral femoral vessels clearly. No significant side effect was noticed in any case. Therefore, this method was thought to be very useful clinically. (author).

  6. Administration costs of intravenous biologic drugs for rheumatoid arthritis

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    Soini, Erkki J.; Leussu, Miina; Hallinen, Taru

    2013-01-01

    Background Cost-effectiveness studies explicitly reporting infusion times, drug-specific administration costs for infusions or real-payer intravenous drug cost are few in number. Yet, administration costs for infusions are needed in the health economic evaluations assessing intravenously-administered drugs. Objectives To estimate the drug-specific administration and total cost of biologic intravenous rheumatoid arthritis (RA) drugs in the adult population and to compare the obtained costs wit...

  7. Cost-minimization of mabthera intravenous versus subcutaneous administration

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    Bax, P.; Postma, M.J.

    2013-01-01

    Objectives: To identify and compare all costs related to preparing and administrating MabThera for the intravenous and subcutaneous formulations in Dutch hematological patients. The a priori notion is that the costs of subcutaneous MabThera injections are lower compared to intravenous infusion due t

  8. Cost-minimization of mabthera intravenous versus subcutaneous administration

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    Bax, P.; Postma, M.J.

    2013-01-01

    Objectives: To identify and compare all costs related to preparing and administrating MabThera for the intravenous and subcutaneous formulations in Dutch hematological patients. The a priori notion is that the costs of subcutaneous MabThera injections are lower compared to intravenous infusion due

  9. Administration and monitoring of intravenous anesthetics

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    Sahinovic, Marko M.; Absalom, Anthony R.; Struys, Michel M. R. F.

    2010-01-01

    Purpose of review The importance of accuracy in controlling the dose-response relation for intravenous anesthetics is directly related to the importance of optimizing the efficacy and quality of anesthesia while minimizing adverse drug effects. Therefore, it is important to measure and control all

  10. Distribution of creatinine following intravenous and oral administration to rats.

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    Watanabe, J; Hirate, J; Iwamoto, K; Ozeki, S

    1981-05-01

    To evaluate the distribution of creatinine in rats, urinary, fecal and expiratory excretion, plasma levels and whole-body autoradiography following intravenous or oral administration of [carbonyl-14C]creatinine was investigated. More than 90% of the exogeneous creatinine was excreted in the urine in 24 hr following intravenous administration, and both fecal and expiratory excretion were only about 1%. In case of oral administration, however, it was found that expiratory excretion could not be neglected, ranging from about 1 to 30%. Plasma creatinine concentration-time curves following the intravenous administration (70.4 micrograms/kg or 400 mg/kg as creatinine) were analyzed according to a two-compartment open model. There were significant but very small differences in the pharmacokinetic parameters for these two doses. When these parameters were compared with those of urea, k12 and k21, which are transfer rate constants between compartment 1 and 2, for creatinine were significantly smaller than those of urea. On the other hand, k10 was larger in creatinine. Furthermore, (V'd)extrap for creatinine was about three times that of urea. Whole-body autoradiograms at 5 minutes following intravenous administration showed that exogeneous creatinine distributes with higher concentrations in liver, lung and kidney than in muscle and fat. This results was remarkably different from that of urea which distributes almost uniformly throughout the body at the same time. This difference observed in the autoradiograms would be the consequence of the fact that urea has larger k12 and k21 than creatinine.

  11. [Administration of intravenous sedation with midazolam by dentists is unsafe].

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    Broers, D L M; Plat, J; de Jongh, A; Zuidgeest, T G M; Blom, H C C M; Kraaijenhagen, A E; Pieterse, C M; Bildt, M M

    2015-03-01

    In the December issue of the Nederlands Tijdschrift voor Tandheelkunde (Dutch Journal of Dentistry) in 2014, an article was devoted to the use of light sedation with midazolam by dentists. A number of dentists who are active in the area of Special Dentistry (anxiety management, care of the disabled) and a anesthesiologist offer a response to the article and argue that the administration of intravenous sedation with midazolam by dentists is unsafe.

  12. Understanding triglyceride levels related to intravenous fat administration.

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    Weaver, Karen

    2014-01-01

    Lipid is an essential macronutrient in parenteral nutrition (PN) support. intravenous (IV) lipid provides essential fatty acids and a concentrated calorie source. Preterm infants are at risk for essential fatty deficiency early in life. Lipid administration is associated with some risks, and there are guidelines for administration to minimize complications. Lipid emulsions in the United States are derived from soybean oil. Outside of the United States, lipid emulsions made from fish oil or combinations of fish, soybean, olive, and medium-chain triglycerides (MCTs) are under investigation for improved tolerance, lower plasma lipid levels, and improved fatty acid profiles, all of which are considered beneficial. Triglyceride levels are an important measurement to assess patient tolerance.

  13. DIAZEPAM IN PEDIATRIC CONVULSION MANAGEMENT: RECTAL VS INTRAVENOUS ADMINISTRATION

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    T MAHMOUDIAN

    2000-06-01

    Full Text Available Introduction. Convulsion is a dangerous occurrence in pediatric disease that requires immediately intervention. It is one of the common causes of referring children to emergency room and must be controlled as soon as possible for prevention of systemic complications and the brain damages. We compared the effect of intravenous (IV versus rectal diazepam in control of convulsion in children.
    Methods. Study group included eighty patients with seizure (from 3 months to 12 years old. Forty patients received rectal diazepam and other ones received diazepam intravenously.
    Results. The convulsion was controlled with rectal diazepam in less than 5 minutes (N diazepam less than 2 minutes and this method was not difficult even for parents.
    Discussion. Control of convulsion less than one minute has no relation to the route of diazepam administration. The important factors for control of seizure are dose of diazepam and the prompt use of it after seizure.

  14. Pharmacokinetics of marbofloxacin, after single intravenous administrations, in buffaloes calves

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    M.I. San Andrés

    2010-02-01

    Full Text Available Marbofloxacin is a synthetic, bactericidal antimicrobial, belonging to the fluoroquinolone group which acts by inhibition of DNA gyrase and those acts by concentration dependant killing mechanism, so high plasma concentration initially is important. This drug is a fluoroquinolone developed exclusively for veterinary use, and exhibit high bactericidal activity against a broad spectrum of aerobic gram-negative, some gram-positive bacteria and Mycoplasma spp. The pharmacokinetic behaviour of marbofloxacin was investigated after intravenous (2 mg/kg in five clinically healthy buffaloes (10 days-old. Plasma concentrations of the marbofloxacin were determined by a HPLC/ u.v. method. After intravenous administration, marbofloxacin in buffaloes was characterized by a AUC = 8,42±3,71 μg·h/ml, a large volume of distribution (Vss=1.59±0.55 L/kg and a long persistence with an elimination half-life (t½λ of 4.6±0,31 h, and MRT 5,90±0,57h. Furthermore, marbofloxacin in buffaloes was characterized by a relatively low total body clearance (Cl of 0.28±0.12 L/kg·h.

  15. Safety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression

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    aan het Rot, Marije; Collins, Katherine A.; Murrough, James W.; Perez, Andrew M.; Reich, David L.; Charney, Dennis S.; Mathew, Sanjay J.

    2010-01-01

    Background: A single subanesthetic (intravenous) IV dose of ketamine might have rapid but transient antidepressant effects in patients with treatment-resistant depression (TRD). Here we tested the tolerability, safety, and efficacy of repeated-dose open-label IV ketamine (six infusions over 12 days)

  16. Pharmacokinetics of marbofloxacin after intravenous and intramuscular administration to ostriches.

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    de Lucas, José Julio; Rodríguez, Casilda; Waxman, Samanta; González, Fernando; Uriarte, Isabel; San Andrés, Manuel Ignacio

    2005-11-01

    The pharmacokinetics of marbofloxacin was investigated after intravenous (IV) and intramuscular (IM) administration, both at a dose rate of 5 mg/kg BW, in six clinically healthy domestic ostriches. Plasma concentrations of marbofloxacin was determined by a HPLC/UV method. The high volume of distribution (3.22+/-0.98 L/kg) suggests good tissue penetration. Marbofloxacin presented a high clearance value (2.19+/-0.27 L/kgh), explaining the low AUC values (2.32+/-0.30 microgh/mL and 2.25+/-0.70 microgh/mL, after IV and IM administration, respectively) and a short half life and mean residence time (t(1/2 beta)=1.47+/-0.31 h and 1.96+/-0.35 h; MRT=1.46+/-0.02 h and 2.11+/-0.30 h, IV and IM, respectively). The absorption of marbofloxacin after IM administration was rapid and complete (C(max)=1.13+/-0.29 microg/mL; T(max)=0.36+/-0.071 h; MAT=0.66+/-0.22 h and F (%)=95.03+/-16.89).

  17. Factors predictive of intravenous fluid administration errors in Australian surgical care wards

    OpenAIRE

    2005-01-01

    Background: Intravenous (IV) fluid administration is an integral component of clinical care. Errors in administration can cause detrimental patient outcomes and increase healthcare costs, although little is known about medication administration errors associated with continuous IV infusions.

  18. Pharmacokinetics of thymoxamine in rabbits after ophthalmic and intravenous administration.

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    Aldana, I; González-Peñas, E; Fos, D; Bruseghini, L; Esteras, A; Ceppi Monti, N; Gianesello, V

    1994-01-01

    The pharmacokinetics of thymoxamine hydrochloride were studied in rabbits by the assessment of its ocular and systemic absorption after instillation of thymoxamine hydrochloride 0.5% eye drops. Plasma levels were compared with those observed after i.v. bolus administration of thymoxamine hydrochloride at 2.5 mg/kg. Deacetylthymoxamine is the main metabolite of thymoxamine, generated by esterase hydrolysis. It was evaluated, as an indication of the parent drug, in aqueous humor and plasma by an HPLC method with fluorescence detection (detection limit = 5 ng/ml). Thymoxamine was found to permeate the cornea and to be hydrolysed very quickly, showing very good absorption with a maximum aqueous humor concentration of deacetylthymoxamine of 2329 ng/ml 15 min after eye drop instillation. The study of the systemic absorption of thymoxamine allowed the exclusion of the possibility of systemic side effects following ocular treatment. In fact, considering the detection limit of the method, the plasma levels of deacetylthymoxamine are certainly more than 100-times lower than those observed with intravenous treatment.

  19. ANTISEPSIS THROUGH INTRAVENOUS AND INTRAMUSCULAR VIA FOR MEDICINE ADMINISTRATION

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    Shirley Ribeiro Cardoso

    2006-04-01

    Full Text Available ABSTRACT: The skin shelters vast micro biota, which could penetrate more internal, layers during the medicine application through parenteral via, therefore the importance of antisepsis for this procedure. We aimed to identify the application of antisepsis through intravenous (IV and intramuscular (IM via for medicine administration as measures for the infection prevention. Descriptive study, accomplished with a nursing team, in eight units from an educational hospital in Goiânia’s district. The data was obtained through observation and filling out the check-list. We observed 212 professionals. As far as the administration via, 19,8% of the procedures were accomplished through direct IV via, 72,6% through IV via with an already installed system and 7,6% through IM via. Most of the professionals, 79,2%, did not wash their hands before accomplishing the procedure. From the 154 medications done in the venous system already installed, the disinfection of the rubber injector was not accomplished in 47 (30,5%. As far as the antisepsis, 72,4% of the medications were accomplished through IV via and 27,6% through IM via, but spite the use of the antiseptic in all the situations, only in 40,5% of the IV injections and in 37,5% of the IM were done five or more movements in the same way with soaked cotton with alcohol at 70%, which is the extolled procedure for the accomplishment for the skin antisepsis. After the antisepsis, 25 professionals touched the place, contaminating it, of these just 13 (52,0% made new antisepsis, therefore, there was recontamination in 12 situations. The data reveals that: necessary measures for the infection prevention in the medicine through parenteral via are not always adopted, representing a challenge for the permanent education and for the infection control at the hospital in study. KEYWORDS: Local Anti-infective Agents; Hospital Infection; Primary Nursing Care.

  20. Prolonged Administration of Twice-Daily Bolus Intravenous Tacrolimus in the Early Phase After Lung Transplantation.

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    Hirano, Yutaka; Sugimoto, Seiichiro; Mano, Toshifumi; Kurosaki, Takeshi; Miyoshi, Kentaroh; Otani, Shinji; Yamane, Masaomi; Kobayashi, Motomu; Miyoshi, Shinichiro; Oto, Takahiro

    2017-08-11

    BACKGROUND Although administration of tacrolimus, whether by the enteric, sublingual, or continuous intravenous routes, has some limitations, twice-daily bolus intravenous tacrolimus administration has been shown to be beneficial in optimizing efficacy and safety after lung transplantation. However, at present, the duration of bolus intravenous tacrolimus administration is limited, and the effects of prolonged bolus intravenous tacrolimus administration remain unknown. Our study was aimed at assessing the safety and efficacy of prolonged twice-daily bolus intravenous tacrolimus administration in the early phase after lung transplantation. MATERIAL AND METHODS We retrospectively investigated the data of 62 recipients of lung transplantation who had received twice-daily bolus intravenous administration of tacrolimus, followed by oral tacrolimus, after lung transplantation at our institution between January 2011 and October 2015. RESULTS The median duration of bolus intravenous tacrolimus administration was 19 days (4-72 days). The target trough level was achieved in 89% of the patients by day 3. Acute kidney injury occurred in 27% of the patients during bolus intravenous tacrolimus. Two patients (3%) had neurotoxicity, necessitating discontinuation of tacrolimus. Suspected acute rejection requiring steroid pulse therapy occurred in 21% of patients during the follow-up period. Eight patients (13%) developed chronic lung allograft dysfunction during the follow-up period. The 1-year and 5-year survival rates after lung transplantation were 95% and 76%, respectively. CONCLUSIONS These results suggest that prolonged bolus intravenous tacrolimus administration in the early phase after lung transplantation is a safe and effective alternative to enteric, sublingual, or continuous intravenous administration.

  1. Pharmacokinetics of flunixin in mature heifers following multiple intravenous administration.

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    Jaroszewski, J; Jedziniak, P; Markiewicz, W; Grabowski, T; Chrostowska, M; Szprengier-Juszkiewicz, T

    2008-01-01

    The pharmacokinetics of flunixin meglumine was determined after its multiple (altogether 4 doses at 24-hours intervals) intravenous administration at a dose of 2.2 mg/kg body weight in six mature clinically healthy heifers. Plasma flunixin and its metabolite 5-hydroxyflunixin concentrations were analyzed with high-pressure liquid chromatography using an assay with a lower limit detection of 0.03 microg/ml for both substances. Plasma concentrations versus time curves were described by a two compartment open model. Mean plasma flunixin concentrations were similar on day 1 and 4, and than rapidly decreased (within 2 hours) from initial concentrations higher than 10 microg/ml to the concentrations lower than 1 microg/ml. The distribution phase of flunixin was short (t0.5 alpha = 0.29 +/- 0.16 and 0.18 +/- 0.04 on day 1 and 4, respectively) and the elimination phase was more prolonged (t0.5 beta = 3.30 +/- 0.60 and 3.26 +/- 0.22 on day 1 and 4, respectively). The mean residence time of flunixin was similar on day 1 (1.83 +/- 0.83) and 4 (1.88 +/- 0.46), and for 5-hydroxyflunixin this parameter was insignificantly (P > 0.05) higher on day 1 (5.49 +/- 2.22) as compared to that found on day 4 (3.99 +/- 2.17). The clearance of flunixin was similar on both examined days (0.23 +/- 0.12 on day 1 and 0.31 +/- 0.15 on day 4), and for 5-hydroxyflunixin was insignificantly (P > 0.05) lower on day 1 (2.37 +/- 1.21) as compared to that determined on day 4 (3.23 +/- 1.06). Our data indicate that multiple administration of flunixin did not alter significantly the parent drug and its metabolite concentrations in plasma, however may cause some small changes in pharmacokinetic parameters.

  2. Repeated administration of adenosine increases its cardiovascular effects in rats.

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    Vidrio, H; García-Márquez, F; Magos, G A

    1987-01-20

    Hypotensive and negative chronotropic responses to adenosine in anesthetized rats increased after previous administration of the nucleoside. Bradycardia after adenosine in the isolated perfused rat heart was also potentiated after repeated administration at short intervals. This self-potentiation could be due to extracellular accumulation of adenosine and persistent stimulation of receptors caused by saturation or inhibition of cellular uptake of adenosine.

  3. Postmarketing review of intravenous acetaminophen dosing based on Food and Drug Administration prescribing guidelines.

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    dela Cruz Ubaldo, Catherine; Hall, Natalie Semaan; Le, Brenden

    2014-12-01

    To evaluate the appropriateness of intravenous acetaminophen dosing-prescribed dose, frequency, duration, and indication-based on United States Food and Drug Administration (FDA)-approved prescribing guidelines and to evaluate the adverse effect profile of intravenous acetaminophen. Retrospective chart review. United States Navy medical center. Three hundred patients who received intravenous acetaminophen from August 1, 2011, to August 1, 2012. The indications, dose, frequency, and duration of intravenous acetaminophen were recorded for each patient. Adverse effects of intravenous acetaminophen were analyzed by thoroughly reviewing any adverse effects documented, including nausea, vomiting, headache, or any symptom specifically attributed to the drug. Baseline liver function tests, including aspartate aminotransferase and alanine aminotransferase levels, and elevations 3 times the upper limit of normal during intravenous acetaminophen therapy were recorded. The average patient weight was 78±21 kg, with 12 patients (4%) weighing less than 50 kg and 288 (96%) patients weighing 50 kg or greater. Two hundred forty-one patients (80%) were appropriately dosed, whereas 59 (20%) patients were not appropriately dosed based on the FDA-approved dosing. No patients exceeded the FDA-approved maximum daily dosing recommendations for intravenous acetaminophen (4 g). Sixty-five patients (22%) received intravenous acetaminophen for longer than 24 hours. Intravenous acetaminophen was well tolerated, without any reported adverse effects, including the commonly reported adverse effects of nausea, vomiting, headache, and insomnia. Ten patients (3%) had a documented history of liver disease and did not experience any adverse effects or increases in liver function tests after the administration of intravenous acetaminophen. Intravenous acetaminophen appeared to be a safe and effective analgesic and antipyretic agent. Dosing for patients weighing less than 50 kg needs to be appropriately

  4. DIAZEPAM IN PEDIATRIC CONVULSION MANAGEMENT: RECTAL VS INTRAVENOUS ADMINISTRATION

    OpenAIRE

    T MAHMOUDIAN

    2000-01-01

    Introduction. Convulsion is a dangerous occurrence in pediatric disease that requires immediately intervention. It is one of the common causes of referring children to emergency room and must be controlled as soon as possible for prevention of systemic complications and the brain damages. We compared the effect of intravenous (IV) versus rectal diazepam in control of convulsion in c...

  5. Intravenous Iron Administration and Hypophosphatemia in Clinical Practice

    OpenAIRE

    Hardy, S.; Vandemergel, X.

    2015-01-01

    Introduction. Parenteral iron formulations are frequently used to correct iron deficiency anemia (IDA) and iron deficiency (ID). Intravenous formulation efficacy on ferritin and hemoglobin level improvement is greater than that of oral formulations while they are associated with lower gastrointestinal side effects. Ferric carboxymaltose- (FCM-) related hypophosphatemia is frequent and appears without clinical significance. The aim of this study was to assess the prevalence, duration, and pote...

  6. Effects of albendazole nanoparticles in mice with hepatic echinococosis: Portal vein cannulation versus intravenous administration.

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    Zhu, Di-Wen; Zhang, Ming-Xing; Bao, Ying-Jun; Gu, Jun-Peng; Ji, Wei-Zheng; Zhang, Hai-Xiao; Ren, Wei-Xin

    2015-07-01

    To compare the ABZ and its metabolites concentration in cyst tissue of hepatic alveolar echinococcosis administered by different routes, forty male Wistar rats receiving albendazole nanoparticles from tail vein and portal vein were divided into two groups, the concentration of ABZ and its metabolites ABZSO, ABZSO2, in the cyst tissue, were analyzed by HPLC at 2, 4, 8, 24, 36 h after administration. The parent drug and its metabolites were detected in plasm and the cyst tissue after portal cannulation and intravenous administration. The last results were the concentration of ABZ in the portal cannulation group was higher than in the intravenous group at every time point (p < 0.05). Compared to the intravenous group, the portal cannulation administration of ABZ led to a lower plasm concentration of ABZ. The concentration of ABZ and the active ABZSO were significantly higher in the portal cannulation group than that of the intravenous group.

  7. [Experiences with intravenous sulprostone administration in massive postpartal hemorrhage].

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    Schönegg, W; Wessel, J; Schmidt-Gollwitzer, K

    1987-11-01

    Forty-three patients at the University Gynecology Clinic in Charlottenburg were given the prostaglandin E2 derivative sulprostone for severe postpartal hemorrhage. It was administered intravenously in a dose of 1.7 mcg/min (100 mcg/100 ml/h), with short-term increases to three times this amount in isolated cases. The drug proved highly efficacious (rapid onset and lasting effect). In 80% of the cases there were no side effects. Rises in body temperature occurred in six patients and in one patient a venous irritation developed in the arm into which the drug was infused. An RDS occurred, though it was considered that there was not necessarily a causal connection between this and the sulprostone infusion. In the authors' experience this drug has an established place in the treatment of atonic postpartal hemorrhage emergencies.

  8. Serotonin function in panic disorder: intravenous administration of meta-chlorophenylpiperazine.

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    Wetzler, S; Asnis, G M; DeLecuona, J M; Kalus, O

    1996-09-27

    A placebo-controlled study of the direct serotonin receptor agonist meta-chlorophenylpiperazine (MCPP), intravenously infused over 90 s in a 0.06 mg/kg dose, was conducted in 10 patients with panic disorder and 9 normal control subjects. Cortisol, MCPP serum levels, and behavioral responses in both groups. Differences between intravenous and oral administration of MCPP are discussed, and the present findings are related to the serotonergic hypothesis of panic disorder.

  9. Pharmacokinetics of melamine in pigs following intravenous administration.

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    Baynes, Ronald E; Smith, Geof; Mason, Sharon E; Barrett, Erica; Barlow, Beth M; Riviere, Jim E

    2008-03-01

    Melamine-contaminated pet food was recently added as a supplement to livestock feed. There is little or no information concerning the pharmacokinetics of melamine in livestock, and the aim of this study was to obtain pharmacokinetic parameters for this contaminant in pigs. Melamine was administered intravenously to five weanling pigs at a dose of 6.13 mg/kg and plasma samples were collected over 24 h, extracted for melamine, and then analyzed by HPLC-UV. The data was shown to best fit a one-compartment model with melamine's half-life of 4.04 (+/- 0.37) h, clearance of 0.11 (+/- 0.01) L/h/kg, and volume of distribution of 0.61 (+/- 0.04) L/kg. These data are comparable to the only mammalian study in rats and suggests that melamine is readily cleared by the kidney and there is unlikely to be significant tissue binding. Further tissue residue studies are required to assess the depletion kinetics of this contaminant in the pig which will determine whether residue levels in the kidney should be of public health concern if pigs were exposed to a similar dose.

  10. Intravenous iron administration and hypophosphatemia in clinical practice.

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    Hardy, S; Vandemergel, X

    2015-01-01

    Introduction. Parenteral iron formulations are frequently used to correct iron deficiency anemia (IDA) and iron deficiency (ID). Intravenous formulation efficacy on ferritin and hemoglobin level improvement is greater than that of oral formulations while they are associated with lower gastrointestinal side effects. Ferric carboxymaltose- (FCM-) related hypophosphatemia is frequent and appears without clinical significance. The aim of this study was to assess the prevalence, duration, and potential consequences of hypophosphatemia after iron injection. Patients and Methods. The medical records of all patients who underwent parenteral iron injection between 2012 and 2014 were retrospectively reviewed. Pre- and postinjection hemoglobin, ferritin, plasma phosphate, creatinine, and vitamin D levels were assessed. Patients who developed moderate (range: 0.32-0.80 mmol/L) or severe (iron preparations but 104 were excluded because of missing data. Among the 130 patients included, 52 received iron sucrose (FS) and 78 FCM formulations. Among FS-treated patients, 22% developed hypophosphatemia versus 51% of FCM-treated patients, including 13% who developed profound hypophosphatemia. Hypophosphatemia severity correlated with the dose of FCM (p = 0.04) but not with the initial ferritin, hemoglobin, or vitamin D level. Mean hypophosphatemia duration was 6 months. No immediate clinical consequence was found except for persistent fatigue despite anemia correction in some patients. Conclusions. Hypophosphatemia is frequent after parenteral FCM injection and may have clinical consequences, including persistent fatigue. Further studies of chronic hypophosphatemia long-term consequences, especially bone assessments, are needed.

  11. Optimizing intravenous drug administration by applying pharmacokinetic/pharmacodynamic concepts

    NARCIS (Netherlands)

    Struys, M. M. R. F.; Sahinovic, M.; Lichtenbelt, B. J.; Vereecke, H. E. M.; Absalom, A. R.

    2011-01-01

    This review discusses the ways in which anaesthetists can optimize anaesthetic-analgesic drug administration by utilizing pharmacokinetic and pharmacodynamic information. We therefore focus on the dose-response relationship and the interactions between i.v. hypnotics and opioids. For i.v. hypnotics

  12. Intravenous Iron Administration and Hypophosphatemia in Clinical Practice

    Directory of Open Access Journals (Sweden)

    S. Hardy

    2015-01-01

    Full Text Available Introduction. Parenteral iron formulations are frequently used to correct iron deficiency anemia (IDA and iron deficiency (ID. Intravenous formulation efficacy on ferritin and hemoglobin level improvement is greater than that of oral formulations while they are associated with lower gastrointestinal side effects. Ferric carboxymaltose- (FCM- related hypophosphatemia is frequent and appears without clinical significance. The aim of this study was to assess the prevalence, duration, and potential consequences of hypophosphatemia after iron injection. Patients and Methods. The medical records of all patients who underwent parenteral iron injection between 2012 and 2014 were retrospectively reviewed. Pre- and postinjection hemoglobin, ferritin, plasma phosphate, creatinine, and vitamin D levels were assessed. Patients who developed moderate (range: 0.32–0.80 mmol/L or severe (<0.32 mmol/L hypophosphatemia were questioned for symptoms. Results. During the study period, 234 patients received iron preparations but 104 were excluded because of missing data. Among the 130 patients included, 52 received iron sucrose (FS and 78 FCM formulations. Among FS-treated patients, 22% developed hypophosphatemia versus 51% of FCM-treated patients, including 13% who developed profound hypophosphatemia. Hypophosphatemia severity correlated with the dose of FCM (p=0.04 but not with the initial ferritin, hemoglobin, or vitamin D level. Mean hypophosphatemia duration was 6 months. No immediate clinical consequence was found except for persistent fatigue despite anemia correction in some patients. Conclusions. Hypophosphatemia is frequent after parenteral FCM injection and may have clinical consequences, including persistent fatigue. Further studies of chronic hypophosphatemia long-term consequences, especially bone assessments, are needed.

  13. Nimodipine in aneurysmal subarachnoid hemorrhage: a randomized study of intravenous or peroral administration

    DEFF Research Database (Denmark)

    Kronvall, Erik; Undrén, Per; Rommer, Bertil Roland;

    2009-01-01

    OBJECT: The calcium antagonist nimodipine has been shown to reduce the incidence of ischemic complications following aneurysmal subarachnoid hemorrhage (SAH). Although most randomized studies have been focused on the effect of the peroral administration of nimodipine, intravenous infusion...... and new cerebral infarctions according to MR imaging studies were recorded. RESULTS: Baseline characteristics (age, sex distribution, clinical status on admission, radiological findings, and aneurysm treatment) did not differ between the treatment groups. There was no significant difference...... of patients with new infarctions on MR imaging. CONCLUSIONS: The results suggest that there is no clinically relevant difference in efficacy between peroral and intravenous administration of nimodipine in preventing DINDs or cerebral vasospasm following SAH....

  14. Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers

    Directory of Open Access Journals (Sweden)

    Nagelschmitz J

    2014-03-01

    Full Text Available J Nagelschmitz,1 M Blunck,1 J Kraetzschmar,1 M Ludwig,1 G Wensing,1 T Hohlfeld2 1Bayer HealthCare AG, Clinical Pharmacology, Wuppertal, Germany; 2Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine Universität Düsseldorf, Düsseldorf, Germany Background: The pharmacology of single doses of acetylsalicylic acid (ASA administered intravenously (250 or 500 mg or orally (100, 300, or 500 mg was evaluated in a randomized, placebo-controlled, crossover study. Methods: Blood and urine samples were collected before and up to 24 hours after administration of ASA in 22 healthy volunteers. Pharmacokinetic parameters and measurements of platelet aggregation were determined using validated techniques. Results: A comparison between administration routes showed that the geometric mean dose-corrected peak concentrations (Cmax/D and the geometric mean dose-corrected area under the curve (AUC0–∞/D were higher following intravenous administration of ASA 500 mg compared with oral administration (estimated ratios were 11.23 and 2.03, respectively. Complete inhibition of platelet aggregation was achieved within 5 minutes with both intravenous ASA doses, reflecting a rapid onset of inhibition that was not observed with oral dosing. At 5 minutes after administration, the mean reduction in arachidonic acid-induced thromboxane B2 synthesis ex vivo was 99.3% with ASA 250 mg intravenously and 99.7% with ASA 500 mg intravenously. In exploratory analyses, thromboxane B2 synthesis was significantly lower after intravenous versus oral ASA 500 mg (P<0.0001 at each observed time point up to the first hour after administration. Concentrations of 6-keto-prostaglandin1α at 5 and 20 minutes after dosing were also significantly lower with ASA 500 mg intravenously than with ASA 500 mg orally. Conclusion: This study demonstrates that intravenous ASA provides more rapid and consistent platelet inhibition than oral ASA within the first hour after dosing

  15. Physiologic effects of intravenous fluid administration in healthy volunteers

    DEFF Research Database (Denmark)

    Holte, Kathrine; Jensen, Peter; Kehlet, Henrik

    2003-01-01

    , infusion of the fluid over 3 h in the morning, and additionally 24-h hospitalization under standardized conditions. Primary outcome assessments were pulmonary function (spirometry), exercise capacity (submaximal treadmill test), balance function (BalanceMaster), and weight. Infusion of 40 mL/kg of lactated...... by fluid administration. These findings may serve as a basis for clinical studies applying the same type of fluid in different amounts to determine the optimal amount of perioperative fluid in various surgical procedures. IMPLICATIONS: Infusion of 40 mL/kg of lactated Ringer's solution in volunteers led...

  16. Pharmacokinetics of meloxicam in koalas (Phascolarctos cinereus) after intravenous, subcutaneous and oral administration.

    Science.gov (United States)

    Kimble, B; Black, L A; Li, K M; Valtchev, P; Gilchrist, S; Gillett, A; Higgins, D P; Krockenberger, M B; Govendir, M

    2013-10-01

    The pharmacokinetic profile of meloxicam in clinically healthy koalas (n = 15) was investigated. Single doses of meloxicam were administered intravenously (i.v.) (0.4 mg/kg; n = 5), subcutaneously (s.c.) (0.2 mg/kg; n = 1) or orally (0.2 mg/kg; n = 3), and multiple doses were administered to two groups of koalas via the oral or s.c. routes (n = 3 for both routes) with a loading dose of 0.2 mg/kg for day 1 followed by 0.1 mg/kg s.i.d for a further 3 days. Plasma meloxicam concentrations were quantified by high-performance liquid chromatography. Following i.v. administration, meloxicam exhibited a rapid clearance (CL) of 0.44 ± 0.20 (SD) L/h/kg, a volume of distribution at terminal phase (Vz ) of 0.72 ± 0.22 L/kg and a volume of distribution at steady state (Vss ) of 0.22 ± 0.12 L/kg. Median plasma terminal half-life (t(1/2)) was 1.19 h (range 0.71-1.62 h). Following oral administration either from single or repeated doses, only maximum peak plasma concentration (C(max) 0.013 ± 0.001 and 0.014 ± 0.001 μg/mL, respectively) was measurable [limit of quantitation (LOQ) >0.01 μg/mL] between 4-8 h. Oral bioavailability was negligible in koalas. Plasma protein binding of meloxicam was ~98%. Three meloxicam metabolites were detected in plasma with one identified as the 5-hydroxy methyl derivative. This study demonstrated that koalas exhibited rapid CL and extremely poor oral bioavailability compared with other eutherian species. Accordingly, the currently recommended dose regimen of meloxicam for this species appears inadequate.

  17. Physiologic effects of intravenous fluid administration in healthy volunteers

    DEFF Research Database (Denmark)

    Holte, Kathrine; Jensen, Peter; Kehlet, Henrik

    2003-01-01

    Dose regimens in perioperative fluid management are rarely evidence based. Therefore, we investigated responses to an IV fluid infusion in healthy volunteers to assess basic physiologic effects of a fluid infusion per se. In a prospective, double-blinded, cross-randomized study, 12 healthy...... volunteers with a median age of 63 yr (range, 59-67 yr) received an infusion of lactated Ringer's solution 40 mL/kg (median, 2820 mL) or 5 mL/kg (median, 353 mL; background infusion) in random order on two separate occasions. The study was designed to mimic the perioperative course with preoperative fasting...... by fluid administration. These findings may serve as a basis for clinical studies applying the same type of fluid in different amounts to determine the optimal amount of perioperative fluid in various surgical procedures. IMPLICATIONS: Infusion of 40 mL/kg of lactated Ringer's solution in volunteers led...

  18. Pharmacokinetics of cytisine after single intravenous and oral administration in rabbits.

    Science.gov (United States)

    Astroug, Henri; Simeonova, Roumiana; Kassabova, Lilia V; Danchev, Nikolay; Svinarov, Dobrin

    2010-03-01

    The aim of this study is to develop a sensitive HPLC method for the quantitative determination of cytisine in serum and to characterize the pharmacokinetic behaviour of cytisine after oral and intravenous administration in rabbits. The pharmacokinetic behaviour of cytisine is studied in male and female New Zealand rabbits after oral and intravenous administration. Cytisine is administered orally (dose of 5 mg/kg b.w.) under fasting condition (12 hours) and intravenously (dose 1 mg/kg b.w.) in the marginal ear vein. Cytisine serum concentrations are measured using a highly selective and sensitive validated HPLC method with UV detection. Linearity of the method is in the range 12-2 400 µg/L; accuracy and precision are both within ± 10%, and the limit of detection is 4 µg/L. Selectivity and stability are also validated. Basic pharmacokinetic parameters of cytisine after single oral and intravenous administration are calculated using TOPFIT software. Pharmacokinetic analysis suggests a rapid but incomplete absorption of cytisine after oral administration.

  19. Pharmacokinetics of amoxicillin-clavulanic acid combination after intravenous and intramuscular administration to turkeys and chickens.

    Science.gov (United States)

    Carceles, C M; Vicente, M S; Escudero, E

    1995-12-01

    The pharmacokinetic behaviour of amoxicillin/clavulanic acid (4:1) combination was studied after intravenous and intramuscular administration of single doses (25 mg/kg body weight) to 15 turkeys and 15 chickens. The objective was to determine whether there are differences between turkeys and chickens in the disposition kinetics of amoxicillin and clavulanic acid. The plasma concentrations-time data were analysed by compartmental pharmacokinetic and non-compartmental methods. The disposition curves for both drugs after intravenous administration were best described by a two-compartment open model in turkeys and chickens. The apparent volumes of distribution of amoxicillin and clavulanic acid were similar in the two species. The body clearances of amoxicillin and clavulanic acid in turkeys were significantly slower than in chickens. The elimination half-life of amoxicillin was similar in turkeys (1.12 +/-0.09 h) and chickens (1.03 +/-0.11 h) after intravenous administration, but that of clavulanic acid differed significantly (P<0.05) between turkeys (1.12 +/-0.03 h) and chickens (0.98 +/- 0.05 h). After intramuscular administration both drugs had a significantly longer half-life (P<0.05) in turkeys and chickens than that after the intravenous treatment. The bioavailability after the intramuscular injection was high and similar with both drugs, but higher values were obtained for chickens than turkeys.

  20. Acute pulmonary edema after intravenous administration of nonionic contrast media: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, Jung Eun; Im, Jung Gi; Chung, Jin Wook; Park, Jae Hyung; Han, Man Chung [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-02-01

    We describe high-resolution CT findings of pulmonary edema following the administration of intravenous nonionic contrast media in a patient who had no previous history of cardiovascular disease; areas of ground glass opacity and interlobular septal thickenings which partly disappeared on scans obtained 90 minutes after the initial scans. The proposed mechanisms of pulmonary edema are briefly discussed.

  1. Varenicline impairs extinction and enhances reinstatement across repeated cycles of nicotine self-administration in rats.

    Science.gov (United States)

    Macnamara, Claire L; Holmes, Nathan M; Westbrook, R Fred; Clemens, Kelly J

    2016-06-01

    Varenicline is a partial nicotine receptor agonist widely prescribed as a smoking cessation medication. Repeated (or long-term) use of varenicline has been proposed as a treatment option for tobacco addiction. However the effect of repeated varenicline use on motivation for nicotine is unknown. Here the intravenous nicotine self-administration paradigm in rats was used to model the consequences of varenicline treatment across repeated cycles of administration, extinction and reinstatement. Rats acquired nicotine self-administration across 20 days before undergoing 6 days of extinction, where each extinction session was preceded by a single injection of varenicline or saline. This was followed by a single varenicline-free nicotine-primed reinstatement test. All rats then reacquired nicotine self-administration for 10 days followed by a second cycle of extinction. Across this period, rats either received a second cycle of varenicline (VAR-VAR) or saline (SAL-SAL), or the alternative treatment (SAL-VAR, VAR-SAL), followed by a final reinstatement test. Treatment with varenicline increased responding across the first cycle of extinction, but did not affect responding in the reinstatement test. Across the second cycle, varenicline again increased responding across extinction, and critically, rats treated with varenicline across cycle 1 and saline across cycle 2 (Group VAR-SAL) exhibited more reinstatement than rats in any other group. The effect of VAR on nicotine seeking was not due to its effects on locomotor activity. Instead, the results suggest that a history of VAR can increase vulnerability to reinstatement/relapse when its treatment is discontinued. The possible mechanisms of this increased vulnerability are discussed.

  2. 3D excretory MR urography: improved image quality with intravenous saline and diuretic administration.

    Science.gov (United States)

    Ergen, F Bilge; Hussain, Hero K; Carlos, Ruth C; Johnson, Timothy D; Adusumilli, Saroja; Weadock, William J; Korobkin, Melvyn; Francis, Isaac R

    2007-04-01

    To assess the effect of diuretic administration on the image quality of excretory magnetic resonance urography (MRU) obtained following intravenous hydration, and to determine whether intravenous hydration alone is sufficient to produce diagnostic quality studies of nondilated upper tracts. A total of 22 patients with nondilated upper tracts were evaluated with contrast-enhanced MRU. All patients received 250 mL of saline intravenously immediately prior to the examination. A total of 11 patients received 10-20 mg furosemide in addition to saline. Imaging was performed with a three-dimensional (3D) and two-dimensional (2D) breathhold spoiled gradient-echo sequences. Excretory MRU images were acquired five minutes after the administration of 0.1 mmol/kg gadolinium and were independently reviewed by two radiologists, who were blinded to the MRU technique. Readers evaluated the calyces, renal pelvis, and ureters qualitatively for degree of opacification, distention, and artifacts on a four-point scale. Statistical analysis was performed using a permutation test. There was no significant disagreement between the two readers (P=0.14). Furosemide resulted in significant improvement in calyceal and renal pelvis distention (PMRU studies obtained following intravenous hydration. Intravenous saline alone is insufficient to produce diagnostic quality studies of the non-dilated upper tracts. Copyright (c) 2007 Wiley-Liss, Inc.

  3. Comparative pharmacokinetics of single doses of doxylamine succinate following intranasal, oral and intravenous administration in rats.

    Science.gov (United States)

    Pelser, Andries; Müller, Douw G; du Plessis, Jeanetta; du Preez, Jan L; Goosen, Colleen

    2002-09-01

    The intranasal route of administration provides a potential useful way of administering a range of systemic drugs. In order to assess the feasibility of this approach for the treatment of nausea and vomiting, doxylamine succinate was studied in rats for the pharmacokinetics (AUC, C(max), t(max)) following intranasal, oral and intravenous administrations. Subjects (six male Sprague-Dawley rats per time interval for each route of administration) received 2-mg doses of doxylamine succinate orally and I-mg doses intranasally and intravenously, respectively. The various formulations were formulated in isotonic saline (0.9% w/v) at 25 +/- 1 degrees C. Doxylamine succinate concentrations in plasma were determined with a high-performance liquid chromatographic assay and a liquid-liquid extraction procedure. Intranasal and oral bioavailabilities were determined from AUC values relative to those after intravenous dosing. Intranasal bioavailability was greater than that of oral doxylamine succinate (70.8 vs 24.7%). The intranasal and oral routes of administration differed significantly from the intravenous route of administration. Peak plasma concentration (C(max)) was 887.6 ng/ml (S.D. 74.4), 281.4 ng/ml (S.D. 24.6) and 1296.4 ng/ml (S.D. 388.9) for the intranasal, oral and intravenous routes, respectively. The time to achieve C(max) for the intranasal route (t(max)=0.5 h) was faster than for the oral route (t(max)=1.5 h), but no statistically significant differences between the C(max) values were found using 95% confidence intervals. The results of this study show that doxylamine succinate is rapidly and effectively absorbed from the nasal mucosa.

  4. Does intravenous administration of recombinant tissue plasminogen activator for ischemic stroke can cause inferior myocardial infarction?

    Directory of Open Access Journals (Sweden)

    Mostafa Almasi

    2016-06-01

    Full Text Available Recombinant tissue plasminogen activator (rTPA is one of the main portions of acute ischemic stroke management, but unfortunately has some complications. Myocardial infarction (MI is a hazardous complication of administration of intravenous rTPA that has been reported recently. A 78-year-old lady was admitted for elective coronary artery bypass graft surgery. On the second day of admission, she developed acute left hemiparesis and intravenous rTPA was administered within 120 minutes. Three hours later, she has had chest pain. Rescue percutaneous coronary intervention was performed on right coronary artery due to diagnosis of inferior MI, and the symptoms were resolved.

  5. Response of the box-jellyfish (Chironex fleckeri) cardiotoxin to intravenous administration of verapamil.

    Science.gov (United States)

    Burnett, J W; Calton, G J

    1983-08-20

    Verapamil, a calcium antagonist, has been shown to be effective in delaying death in mice after intravenous challenge with box-jellyfish (Chironex fleckeri) venom. Death from a challenge of up to three mouse-lethal doses of venom was significantly delayed after the prior intravenous administration of verapamil (P = 0.003). A smaller dose of verapamil could "rescue" mice previously envenomed with 1.25 mouse-lethal doses (P = 0.0001). These data suggest that verapamil injections should be added to the first-aid procedures performed on the beach for victims of box-jellyfish stings.

  6. Safety of Moxifloxacin following repeated intramuscular administration in Wistar rats

    Directory of Open Access Journals (Sweden)

    K.A. Sadariya

    Full Text Available Moxifloxacin is a novel fourth generation fluoroquinolone with broad spectrum of antibacterial activity. The study was conducted to evaluate the safety of Moxifloxacin (5.0 mg/kg after repeated intramuscular administration at 24 h interval for 14 days in male and female wistar rats. Hematological (Haemoglobin, RBC, WBC, MCV, MCH, MCHC, HCT and DLC, blood biochemical parameters (AST, ALT, ALP, Total Bilirubin, Total Serum Protein, Serum Albumin, Globulin, Serum Creatinine, Urea, Uric acid and Blood glucose and histopathological examination of various tissues were carried out in the present study. Male and female animals of any group did not reveal any clinical symptoms and mortality attributable to the 14 days intramuscular administration of Moxifloxacin. The data were compared by unpaired two tail `t` test using Graph Pad Prism (Version 4.00. All above hematological and blood biochemical parameters were found to fluctuate within normal range during treatment period and the mean values were not significantly differ (p < 0.05 from corresponding control values. Moreover, no gross or microscopic changes were found in the liver, kidney, heart, spleen, stomach, intestine and joint cartilages of the treated wistar rats. Results indicate that daily administration of Moxifloxacin for 14 days seems to be safe and well tolerated in rats. [Veterinary World 2010; 3(10.000: 449-452

  7. Pharmacokinetics of amoxicillin/clavulanic acid combination after intravenous and intramuscular administration to pigeons.

    Science.gov (United States)

    Escudero, E; Vicente, M S; Carceles, C M

    1998-01-01

    The pharmacokinetics of amoxicillin/clavulanic acid (4:1) combination were studied after intravenous and intramuscular administration of single doses (25 mg kg(-1) bodyweight) to 50 pigeons. The plasma concentrations-time data were analysed by compartmental pharmacokinetics and non-compartmental methods. The disposition curves for both drugs after intravenous administration were best described by a two-compartment open model. The apparent volumes of distribution of amoxicillin and clavulanic acid were 1.77 litres kg(-1) and 1.30 litres kg(-1) respectively. The body clearances of amoxicillin and clavulanic acid were not significantly different. The elimination half-lives of amoxicillin after intravenous and intramuscular administration were 1.22 (0.09) hour and 1.52 (0.09) hour respectively, and those of clavulanic acid were 1.15 (0.08) hour and 1.49 (0.08) hour. After intramuscular administration both drugs had a significantly longer half-life (P or =0.5 mg litre(-1) (minimum inhibitory concentration of most susceptible pathogens).

  8. Pharmacokinetics and skin concentrations of lincomycin after intravenous and oral administration to cats

    Directory of Open Access Journals (Sweden)

    Gabriela A. Albarellos

    2013-02-01

    Full Text Available The aim of the present study was to describe the plasma pharmacokinetic profile and skin concentrations of lincomycin after intravenous administration of a 15% solution and oral administration of 300 mg tablets at a dosing rate of 15 mg/kg to cats. Susceptibility of staphylococci (n = 31 and streptococci (n = 23 strains isolated from clinical cases was also determined. Lincomycin plasma and skin concentrations were determined by microbiological assay using Kocuria rhizophila ATCC 9341 as test microorganism. Susceptibility was established by the antimicrobial disc diffusion test. Individual lincomycin plasma concentration–time curves were analysed by a non-compartmental approach. After intravenous administration, volume of distribution, body clearance and elimination half-life were 0.97 L/kg ± 0.15 L/kg, 0.17 L/kg ± 0.06 L/h.kg and 4.20 h ± 1.12 h, respectively. After oral administration, peak plasma concentration, time of maximum plasma concentration and bioavailability were 22.52 µg/mL ± 10.97 µg/mL, 0.80 h ± 0.11 h and 81.78% ± 24.05%, respectively. Two hours after lincomycin administration, skin concentrations were 17.26 µg/mL ± 1.32 µg/mL (intravenous and 16.58 µg/mL ± 0.90 µg/mL (oral. The corresponding skin: plasma ratios were 2.08 ± 0.47 (intravenous and 1.84 ± 0.97 (oral. The majority of staphylococci and streptococci tested in this study were susceptible to lincosamides (87.09% and 69.56%, respectively. In conclusion, lincomycin administered orally at the assayed dose showed a good pharmacokinetic profile, with a long elimination half-life and effective skin concentration. Therefore, it could be a good first option for treating skin infections in cats.

  9. Toxicity after prolonged (more than four weeks administration of intravenous colistin

    Directory of Open Access Journals (Sweden)

    Bliziotis Ioannis A

    2005-01-01

    Full Text Available Abstract Background The intravenous use of polymyxins has been considered to be associated with considerable nephrotoxicity and neurotoxicity. For this reason, the systemic administration of polymyxins had been abandoned for about 20 years in most areas of the world. However, the problem of infections due to multidrug-resistant (MDR Gram-negative bacteria such us Pseudomonas aeruginosa and Acinetobacter baumanniii has led to the re-use of polymyxins. Our objective was to study the toxicity of prolonged intravenous administration of colistin (polymyxin E. Methods An observational study of a retrospective cohort at "Henry Dunant" Hospital, a 450-bed tertiary care center in Athens, Greece, was undertaken. Patients who received intravenous colistin for more than 4 weeks for the treatment of multidrug resistant Gram-negative infections were included in the study. Serum creatinine, blood urea, liver function tests, symptoms and signs of neurotoxicity were the main outcomes studied. Results We analyzed data for 19 courses of prolonged intravenous colistin [mean duration of administration (± SD 43.4 (± 14.6 days, mean daily dosage (± SD 4.4 (± 2.1 million IU, mean cumulative dosage (± SD 190.4 (± 91.0 million IU] in 17 patients. The median creatinine value increased by 0.25 mg/dl during the treatment compared to the baseline (p Conclusions No serious toxicity was observed in this group of patients who received prolonged intravenous colistin. Colistin should be considered as a therapeutic option in patients with infections due to multidrug resistant Gram-negative bacteria.

  10. AMS method validation for quantitation in pharmacokinetic studies with concomitant extravascular and intravenous administration.

    Science.gov (United States)

    Lappin, Graham; Seymour, Mark; Young, Graeme; Higton, David; Hill, Howard M

    2011-02-01

    A technique has emerged in the past few years that has enabled a drug's intravenous pharmacokinetics to be readily obtained in humans without having to conduct extensive toxicology studies by this route of administration or expand protracted effort in formulation. The technique involves the intravenous administration of a low dose of (14)C-labelled drug (termed a tracer dose) concomitantly with a non-labelled extravascular dose given at therapeutically levels. Plasma samples collected over time are analysed to determine the total parent drug concentration by LC-MS (which essentially measures that arising from the oral dose) and by LC followed by accelerator mass spectrometry (AMS) to determine the (14)C-drug concentration (i.e., that arising from the intravenous dose). There are currently no published accounts of how the principles of bioanalytical validation might be applied to intravenous studies using AMS as an analytical technique. The authors describe the primary elements of AMS when used with LC separation and how this off-line technique differs from LC-MS. They then discuss how the principles of bioanalytical validation might be applied to determine selectivity, accuracy, precision and stability of methods involving LC followed by AMS analysis.

  11. Pharmacokinetic Study and Tissue Distribution of Single Mangiferin After Intravenous Administration in Rats

    Institute of Scientific and Technical Information of China (English)

    LI Yu-juan; SUI Ying-jie; XIN Nian

    2009-01-01

    A simple,sensitive ane selective high performance liquid chromatographic (HPLC) method with UV detection (320 nm) was developed and validated for determination of mangiferin in rat phsma and tissues.Mangiferin and internal standard (spinosin) were separated using mobile phase of aeetonitrile-water (20:80,v/v) with 1% glacial acetic acid and 1% THF on a Phenomenex gemini C18 column.The flow rate was 0.7 mL/min.The calibration curves of mangiferin in plasma and tissues were linear over the investigated ranges.The intra- and inter-run precisions for all samples were less than 13.8%.The time-concentration curve of mangiferin after intravenous administration to rats corresponded to two-compartment model.The brain,respectively.Mangiferin was not found in liver.After intravenous administration,the drug was distributed extensively and transferred quickly in rats in vivo.

  12. Persistent renal enhancement after intra-arterial versus intravenous iodixanol administration

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Shinn-Huey; Wang, Zhen J.; Kuo, Jonathan; Cabarrus, Miguel; Fu Yanjun; Aslam, Rizwan; Yee, Judy; Zimmet, Jeffrey M.; Shunk, Kendrick; Elicker, Brett [Department of Radiology, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0628 (United States); Yeh, Benjamin M., E-mail: Benjamin.Yeh@ucsf.edu [Department of Radiology, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0628 (United States)

    2011-11-15

    Purpose: To examine the clinical significance of persistent renal enhancement after iodixanol administration. Methods: We retrospectively studied 166 consecutive patients who underwent non-enhanced abdominopelvic CT within 7 days after receiving intra-arterial (n = 99) or intravenous (n = 67) iodixanol. Renal attenuation was measured for each non-enhanced CT scan. Persistent renal enhancement was defined as CT attenuation >55 Hounsfield units (HU). Contrast-induced nephropathy (CIN) was defined as a rise in serum creatinine >0.5 mg/dL within 5 days after contrast administration. Results: While the intensity and frequency of persistent renal enhancement was higher after intra-arterial (mean CT attenuation of 73.7 HU, seen in 54 of 99 patients, or 55%) than intravenous contrast material administration (51.8 HU, seen in 21 of 67, or 31%, p < 0.005), a multivariate regression model showed that the independent predictors of persistent renal enhancement were a shorter time interval until the subsequent non-enhanced CT (p < 0.001); higher contrast dose (p < 0.001); higher baseline serum creatinine (p < 0.01); and older age (p < 0.05). The route of contrast administration was not a predictor of persistent renal enhancement in this model. Contrast-induced nephropathy was noted in 9 patients who received intra-arterial (9%) versus 3 who received intravenous iodixanol (4%), and was more common in patients with persistent renal enhancement (p < 0.01). Conclusion: Persistent renal enhancement at follow-up non-contrast CT suggests a greater risk for contrast-induced nephropathy, but the increased frequency of striking renal enhancement in patients who received intra-arterial rather than intravenous contrast material also reflects the larger doses of contrast and shorter time to subsequent follow-up CT scanning for such patients.

  13. Pharmacokinetics of amoxicillin/clavulanic acid combination after intravenous and oral administration in goats.

    Science.gov (United States)

    Carceles, C M; Escudero, E; Vicente, M S; Serrano, J M; Carli, S

    1995-12-01

    The intravenous and oral pharmacokinetics of an amoxicillin and clavulanic acid combination (20 mg/kg of sodium amoxicillin and 5 mg/kg of potassium clavulanate) were studied in six goats. After intravenous administration the pharmacokinetics of both drugs could be described by an open two-compartment model. Amoxicillin had a greater distribution volume (0.19 +/- 0.01 l/kg) than clavulanic acid (0.15 +/- 0.01 l/kg), whereas the distribution and elimination constants were higher for the latter, which was eliminated more quickly than amoxicillin. After oral administration of both drugs their pharmacokinetic behaviour was best described by an open one-compartment model with first-order absorption. Elimination half-lives were twice as long after oral (2.15 +/- 0.20 h and 1.94 +/- 0.16 h for amoxicillin and clavulanic acid respectively) than after intravenous administration (1.20 +/- 0.16 h and 0.86 +/- 0.09, respectively). An apparent 'flip-flop' situation was evident in this study. Bioavailability was 27% for amoxicillin and 50% for clavulanic acid.

  14. Influence of cue-conditioning on acquisition, maintenance and relapse of cocaine intravenous self-administration.

    Science.gov (United States)

    Deroche-Gamonet, Véronique; Piat, Frédéric; Le Moal, Michel; Piazza, Pier Vincenzo

    2002-04-01

    Conditioning theories propose that, through a Pavlovian associative process, discrete stimuli acquire the ability to elicit neural states involved in the maintenance and relapse of a drug-taking behaviour. Experimental evidence indicates that drug-related cues play a role in relapse, however, their influence on the development and maintenance of drug self-administration has been poorly investigated. In this report, we analysed the effects of a drug-associated cue light on acquisition, maintenance and reinstatement of intravenous cocaine self-administration. The results show that a cocaine-associated cue light can act as an incentive in absence of the drug, but does not directly modify drug-reinforcing effects. Contingent and non-contingent presentations of a cocaine-associated cue light reinstated an extinguished self-administration behaviour. However, regardless of whether or not a cue light was associated with cocaine infusions, rats acquire cocaine intravenous self-administration reaching the same levels of intake. Furthermore, after self-administration has been acquired in presence of the cue light, the omission of the cue light or its non-contingent presentation did not modify rat behaviour. In conclusion, our work shows that cocaine-associated explicit cues do not directly interfere with the reinforcing effects of the drug.

  15. No reactive hypoglycaemia in Type 2 diabetic patients after subcutaneous administration of GLP-1 and intravenous glucose

    DEFF Research Database (Denmark)

    Vilsbøll, Tina; Krarup, T; Madsbad, S;

    2001-01-01

    It has previously been shown that intravenous and subcutaneous administration of glucagon-like peptide (GLP)-1 concomitant with intravenous glucose results in reactive hypoglycaemia in healthy subjects. Since GLP-1 is also effective in Type 2 diabetic patients and is presently being evaluated...

  16. Intravenous Vitamin C administration reduces fatigue in office workers: a double-blind randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Suh Sang-Yeon

    2012-01-01

    Full Text Available Abstract Background Studies of the efficacy of vitamin C treatment for fatigue have yielded inconsistent results. One of the reasons for this inconsistency could be the difference in delivery routes. Therefore, we planned a clinical trial with intravenous vitamin C administration. Methods We evaluated the effect of intravenous vitamin C on fatigue in office workers. A group of 141 healthy volunteers, aged 20 to 49 years participated in this randomized, double-blind, controlled clinical trial. The trial group received 10 grams of vitamin C with normal saline intravenously, while the placebo group received normal saline only. Since vitamin C is a well-known antioxidant, oxidative stress was measured. Fatigue score, oxidative stress, and plasma vitamin C levels were measured before intervention, and again two hours and one day after intervention. Adverse events were monitored. Results The fatigue scores measured at two hours after intervention and one day after intervention were significantly different between the two groups (p = 0.004; fatigue scores decreased in the vitamin C group after two hours and remained lower for one day. Trial also led to higher plasma vitamin C levels and lower oxidative stress compared to the placebo group (p Conclusion Thus, intravenous vitamin C reduced fatigue at two hours, and the effect persisted for one day. There were no significant differences in adverse events between two groups. High dose intravenous vitamin C proved to be safe and effective against fatigue in this study. Trial Registration The clinical trial registration of this trial is http://ClinicalTrials.govNCT00633581.

  17. Pharmacokinetics of ketoprofen enantiomers following intravenous and oral administration to exercised Thoroughbred horses.

    Science.gov (United States)

    Knych, Heather K; Arthur, Rick M; Steinmetz, Stacy; McKemie, Dan S

    2016-01-01

    Ketoprofen (KTP) is currently only available as an injectable formulation for intravenous administration to horses. The primary goal of the study reported here was to characterize the pharmacokinetics of KTP, including determination of bioavailability following oral administration of the currently available injectable formulation as well as a paste formulation. KTP was administered intravenously and orally, and blood and urine samples were collected at various time points up to 96 h. KTP enantiomer concentrations were determined using LC–MS/MS, and pharmacokinetic analyses were performed. Mean ± standard error values for systemic clearance, steady state volume of distribution and terminal elimination half-life were 0.345 ± 0.033 [R(−) KTP] and 0.167 ± 0.016 [S(+) KTP] L/kg/h, 0.344 ± 0.044 [R(−) KTP] and 0.298 ± 0.025 [S(+) KTP] L/kg, and 2.49 ± 0.077 [R(−) KTP] and 2.86 ± 0.102 [S(+) KTP] h, respectively. Oral bioavailability was calculated as 69.5 ± 10.3% and 88.2 ± 15.9% for R(−) KTP and S(+) KTP, respectively, following administration of the injectable formulation and 53.0 ± 6.0 and 53.0 ± 16.0% for the R(−) KTP and S(+) KTP, respectively, following administration of KTP paste.

  18. Comparative study of clindamycin concentration in the cerebrospinal fluid after intravenous and intrathecal administration in patients with toxoplasmic meningoencephalitis

    Directory of Open Access Journals (Sweden)

    Сергій Петрович Борщов

    2015-07-01

    Full Text Available Aim of the work: to study the difference of clindamycin concentration in CSF at the intravenous and combined (intrathecal + intravenous ways of administration of preparation.Materials and methods: study was carried out at the treatment of 11 HIV-positive patients 27-63 years old (men and women with toxoplasmic meningoencephalitises.There was measured the clindamycin concentration in CSF of every patient after intravenous and combined (intrathecal + intravenous ways of administration of preparation. The determinations of concentration were done by the way of the reverse-phase high-performance liquid chromatography (HPLC with ultraviolet (UV detection. Statistic processing of the received data was carried out using the Wilcoxon criterion.Results of research. There was received the statistically significant increase of clindamycin concentration in CSF of patients in a day after combined (intrathecal + intravenous administration of preparation comparing with an intravenous administration.Conclusions. 1. Intrathecal administration of 150 mg. of clindamycin with 8 mg. of dexamethasone is safe.2. Intrathecal administration of 150 mg. of clindamycin with 8 mg. of dexamethasone in combination with an intravenous administration of preparation leads to statistically significant increase of clindamycin concentration in CSF at least during a day after injection.3. Intrathecal administration of clindamycin with dexamethasone in offered doses can be recommended for treatment of meningoencephalitises that caused by microorganisms susceptible to clindamycin.4. If the therapy of toxoplasmic meningoencephalitis was started with an intravenous prescription of clindamycin it is recommended an additional treatment with an intrathecal administration of clindamycin with dexamethasone in offered doses to increase efficiency by creating an effective concentration of preparation in the nidus of infection.5. Intrathecal methods of therapy must be used by the specialists of

  19. Biodistribution of gold nanoparticles synthesized by γ-irradiation after intravenous administration in mice

    Science.gov (United States)

    Luan Le, Quang; Phuong Linh Do, Thi; Phuong Uyen Nguyen, Huynh; Phu Dang, Van; Hien Nguyen, Quoc

    2014-06-01

    In the present research work we evaluate the in vivo distribution of gold nanoparticles (AuNPs) at different time durations after intravenous administration in mice. AuNPs with size of about 20 nm and concentration of 1 mM were synthesized by gamma irradiation method using 0.5% alginate as a stabilizer. AuNPs were characterized by UV-Vis spectrum and transmission electron microscope (TEM) image. The as-synthesized AuNPs solution was centrifuged to concentrate to 2 mg AuNPs/1 ml solution. Intravenous administration of AuNPs in mice was done at the tail with 1 mg AuNPs (0.5 ml). After 1, 3, 6 and 12 h of injection, blood was collected, mice were sacrificed and various tissues/organs were removed. The blood haematology and serum clinical chemistry indexes of mice intravenously injected with AuNPs were not significantly different compared to those of the control ones. In addition, gold content in the samples was quantitatively determined by k0-neutron activation analysis (k0-NAA) at nuclear research reactor, Da Lat Vietnam. Results showed that after 1 h of administration, AuNPs were mainly accumulated in blood (41.56%), in liver (51.60.%), in lung (6.16%) and in kidney (0.53%). After that the content of AuNPs in blood was decreased to nearly normal at 6 h while the content of AuNPs in liver, lung and kidney was accumulatively increased. After 6 h of administration AuNPs were mainly accumulated in organs like liver (76.33%), lung (11.86%) and kidney (2.23%). Thus, the obtained results are practically useful for using AuNPs as x-ray contrast agent, especially for blood and liver.

  20. Pharmacokinetics of CPU0213, a novel endothelin receptor antagonist, after intravenous administration in mice

    Institute of Scientific and Technical Information of China (English)

    Li GUAN; Yu FENG; Min JI; De-zai DAI

    2006-01-01

    Aim: To determine the pharmacokinetics associated with acute toxic doses of CPU0213, a novel endothelin receptor antagonist in mice after a single intravenous administration. Methods: Concentrations in serum and the pharmacokinetic parameters of CPU0213 were assayed by high pressure liquid chromatography (HPLC) following a single intravenous bolus of CPU0213 at concentrations of 25, 50, and 100 mg/kg in mice. The intravenous acute toxicity of CPU0213 was also assessed in mice. Results: A simple, sensitive and selective HPLC method was developed for quantitative determination of CPU0213 in mouse serum. The concentration-time data conform to a 2-compartment model after iv administration of CPU0213 at concentrations of 25, 50,100 mg/kg. The corresponding distribution half-lives (T1/2α) were 3.6, 4.2, 1.1 min and the elimination half-lives (T1/2β) were 39.4,70.3,61.9 min. There was a linear increase in C0 proportional to dose, and the same as AUC0-t and AUC0-∞. AUC0-t and AUC0-∞ were 4.511,13.070,23.666 g·min·L-1 and 4.596,13.679,24.115 g·min·L-1, respectively. The intravenous LD50 was 315.5 mg/kg. Conclusion: First order rate pharmacokinetics were observed for CPU0213 within the range of doses used, and the acute toxicity of CPU0213 is mild.

  1. Comparative pharmacokinetics of fluralaner in dogs and cats following single topical or intravenous administration.

    Science.gov (United States)

    Kilp, Susanne; Ramirez, Diana; Allan, Mark J; Roepke, Rainer Ka

    2016-05-31

    Bravecto™ Chewable Tablets for Dogs, containing fluralaner as active ingredient, is an innovative treatment for flea and tick infestations that provides safe, rapid and long acting efficacy after a single oral administration in dogs. Topically applied fluralaner provides similar safe, rapid and long acting efficacy, both in dogs and in cats. The pharmacokinetic profile of fluralaner was evaluated in dogs and in cats following either topical or intravenous administration. Twenty four dogs and 24 cats received three different topical doses, with the mid-dose based on the respective minimum recommended dose, and one intravenous dose. Plasma samples were collected for 112 days and fluralaner concentrations were quantified using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method. Pharmacokinetic parameters were calculated using non-compartmental methods. In dogs, fluralaner was readily absorbed from the topical administration site into the skin, subjacent tissues and blood. Fluralaner plasma concentrations showed an apparent plateau between ~ day 7 and 63, with individual tmax seen within this time period. After the plasma plateau, concentrations declined slowly and were quantifiable for more than 12 weeks. In cats, fluralaner was readily systemically absorbed from the topical administration site, reaching maximum concentrations (Cmax) in plasma between 3 and 21 days post administration, after which concentrations declined slowly, and were also quantifiable for more than 12 weeks. Systemic exposure, as shown by Cmax and the area under the concentration versus time curve from time 0 to the last measurable concentration (AUC(0→t)) increased proportionally with dose in both species. Following intravenous administration fluralaner showed a relatively high apparent volume of distribution (Vz), a low plasma clearance (Cl), a long terminal half-life (t1/2) and a long mean residence time (MRT); thereby demonstrating

  2. Cocaine self-administration punished by intravenous histamine in adolescent and adult rats.

    Science.gov (United States)

    Holtz, Nathan A; Carroll, Marilyn E

    2015-06-01

    Adolescence is a transitional phase marked by a heightened vulnerability to substances of abuse. It has been hypothesized that both increased sensitivity to reward and decreased sensitivity to aversive events may drive drug-use liability during this phase. To investigate possible age-related differences in sensitivity to the aversive consequences of drug use, adolescent and adult rats were compared on self-administration of cocaine before, during, and after a 10-day period in which an aversive agent, histamine, was added to the cocaine solution. Adult and adolescent female rats were trained to self-administer intravenous cocaine (0.4 mg/kg/infusion) over 10 sessions (2 h/session; 2 sessions/day). Histamine (4 mg/kg/infusion) was then added directly into the cocaine solution for the next 10 sessions. Finally, the cocaine/histamine solution was replaced with a cocaine-only solution, and rats continued to self-administer cocaine (0.4 mg/kg) for 20 sessions. Compared with adolescent rats, adult rats showed a greater decrease in cocaine self-administration when it was punished with intravenous histamine compared with their baseline cocaine self-administration rates. These results suggest that differences in the sensitivity to negative consequences of drug use may partially explain developmental differences in drug use vulnerability.

  3. Efficacy of Lychnopholide Polymeric Nanocapsules after Oral and Intravenous Administration in Murine Experimental Chagas Disease.

    Science.gov (United States)

    de Mello, Carlos Geraldo Campos; Branquinho, Renata Tupinambá; Oliveira, Maykon Tavares; Milagre, Matheus Marques; Saúde-Guimarães, Dênia Antunes; Mosqueira, Vanessa Carla Furtado; Lana, Marta de

    2016-09-01

    The etiological treatment of Chagas disease remains neglected. The compounds available show several limitations, mainly during the chronic phase. Lychnopholide encapsulated in polymeric nanocapsules (LYC-NC) was efficacious in mice infected with Trypanosoma cruzi and treated by intravenous administration during the acute phase (AP). As the oral route is preferred for treatment of chronic infections, such as Chagas disease, this study evaluated the use of oral LYC-NC in the AP and also compared it with LYC-NC administered to mice by the oral and intravenous routes during the chronic phase (CP). The therapeutic efficacy was evaluated by fresh blood examination, hemoculture, PCR, and enzyme-linked immunosorbent assay (ELISA). The cure rates in the AP and CP were 62.5% and 55.6%, respectively, upon oral administration of LYC-poly(d,l-lactide)-polyethylene glycol nanocapsules (LYC-PLA-PEG-NC) and 57.0% and 30.0%, respectively, with LYC-poly-ε-caprolactone nanocapsules (LYC-PCL-NC). These cure rates were significantly higher than that of free LYC, which did not cure any animals. LYC-NC formulations administered orally during the AP showed cure rates similar to that of benznidazole, but only LYC-NC cured mice in the CP. Similar results were achieved with intravenous treatment during the CP. The higher cure rates obtained with LYC loaded in PLA-PEG-NC may be due to the smaller particle size of these NC and the presence of PEG, which influence tissue diffusion and the controlled release of LYC. Furthermore, PLA-PEG-NC may improve the stability of the drug in the gastrointestinal tract. This work is the first report of cure of experimental Chagas disease via oral administration during the CP. These findings represent a new and important perspective for oral treatment of Chagas disease.

  4. Sudden death after intravenous administration of a perflutren contrast agent: a case of pseudocomplication?

    Science.gov (United States)

    Mahjoub, Haïfa; Roméo, Philippe; Leung, Tack-Ki; Burelle, Denis; Cartier, Raymond; Basmadjian, Arsène J

    2009-06-01

    Perflutren cardiac ultrasound agents improve diagnostic accuracy in patients whose imaging is technically difficult. This report describes a case of sudden death approximately 5 minutes after the intravenous administration of 0.5 mL of perflutren contrast agent (Definity) during transthoracic echocardiography with suboptimal baseline images performed 10 days after coronary artery bypass graft surgery because of hypotension and tachycardia in a 73-year-old patient with severe left ventricular systolic dysfunction. Autopsy did not reveal a clear direct relationship between perflutren and death. This is the first reported case of death related temporally to an echocardiographic contrast agent occurring in Canada and could represent a case of pseudocomplication.

  5. Pharmacokinetics of (14) C-ortho-phenylphenol following intravenous administration in pigs.

    Science.gov (United States)

    Nixon, Emma; Brooks, James D; Routh, Patricia A; Chittenden, Jason T; Baynes, Ronald E

    2017-04-01

    Workers in the USA are exposed to industrial formulations, which may be toxic. These formulations often contain preservatives or biocides such as ortho-phenylphenol (OPP). There are limited data describing OPP following intravenous administration to assess truly the clearance of this chemical in humans and other species. In vivo experiments were conducted in pigs to determine related pharmacokinetic parameters. (14) C-OPP was administered as an intravenous bolus dose. Blood, feces, urine and tissue samples were collected for analysis by liquid scintillation. Data were analyzed using non-compartmental and compartmental pharmacokinetic model approaches. These data fitted a three-compartment model and showed that the half-life of (14) C-OPP following the intravenous bolus in pigs was 46.26 ± 10.01 h. The kidneys play a crucial role in clearance of (14) C-OPP with a large percentage of the dose being found in the urine (70.3 ± 6.9% dose). Comparisons with other species suggest that (14) C-OPP clearance in pigs (2.48 ml h(-1)  kg(-1) ) is less than that in humans (18.87 ml h(-1)  kg(-1) ) and rats (35.51 ml h(-1)  kg(-1) ). Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Repeated Intra-Arterial Thrombectomy within 72 Hours in a Patient with a Clear Contraindication for Intravenous Thrombolysis

    Directory of Open Access Journals (Sweden)

    Mona Laible

    2015-01-01

    Full Text Available Introduction. Treating patients with acute ischemic stroke, proximal arterial vessel occlusion, and absolute contraindication for administering intravenous recombinant tissue plasminogen activator (rtPA poses a therapeutic challenge. Intra-arterial thrombectomy constitutes an alternative treatment option. Materials and Methods. We report a case of a 57-year-old patient with concomitant gastric adenocarcinoma, who received three intra-arterial thrombectomies in 72 hours due to repeated occlusion of the left medial cerebral artery (MCA. Findings. Intra-arterial recanalization of the left medial cerebral artery was performed three times with initially good success. However, two days later, the right medial cerebral artery became occluded. Owing to the overall poor prognosis at that time and knowing the wishes of the patient, we decided not to perform another intra-arterial recanalization procedure. Conclusion. To our knowledge, this is the first case illustrating the use of repeated intra-arterial recanalization in early reocclusion of intracranial vessels.

  7. Dose-dependent pharmacokinetics and brain penetration of rufinamide following intravenous and oral administration to rats.

    Science.gov (United States)

    Gáll, Zsolt; Vancea, Szende; Szilágyi, Tibor; Gáll, Orsolya; Kolcsár, Melinda

    2015-02-20

    Rufinamide is a third-generation antiepileptic drug, approved recently as an orphan drug for the treatment of Lennox-Gastaut syndrome. Although extensive research was conducted, its pharmacokinetics in rats was not described. This work addresses that area by describing in a rapid pharmacokinetic study the main pharmacokinetic properties of rufinamide at three different doses of 1 mg/kg body weight (bw), 5 mg/kg bw, and 20 mg/kg bw. Furthermore, total brain concentrations of the drug were determined in order to characterize its brain-to-plasma partition coefficient. Adult Wistar male rats, weighing 200-450 g, were administered rufinamide by intravenous and oral routes. Rufinamide concentrations from plasma samples and brain tissue homogenate were determined using a liquid chromatography-mass spectrometric method and pharmacokinetic parameters were calculated. The mean half-life was between 7 and 13 h, depending on route of administration--intravenously administered drug was eliminated faster than orally administered drug. Mean (S.E.M.) total plasma clearance was 84.01 ± 3.80 ml/h/kg for intravenous administration, while the apparent plasma clearance for oral administration was 95.52 ± 39.45 ml/h/kg. The mean (S.E.M.) maximum plasma concentration reached after oral administration of 1 mg/kg bw and 5 mg/kg bw was 0.89 ± 0.09 μg/ml and 3.188 ± 0.71 μg/ml, respectively. The median (range) time to reach maximum plasma concentration (t(max)) was 4 (2-8)h. Mean (S.E.M.) brain-to-plasma concentration ratio of rufinamide was 0.514 ± 0.036, consistent with the brain-to-plasma ratio calculated from the area under curves (AUC(0-t)) of 0.441 ± 0.047. No influence of dose, route of administration, or post-dosing time was observed on brain-to-plasma ratio.

  8. Oxidative stress, HDL functionality and effects of intravenous iron administration in women with iron deficiency anemia.

    Science.gov (United States)

    Meroño, Tomás; Dauteuille, Carolane; Tetzlaff, Walter; Martín, Maximiliano; Botta, Eliana; Lhomme, Marie; Saez, María Soledad; Sorroche, Patricia; Boero, Laura; Arbelbide, Jorge; Chapman, M John; Kontush, Anatol; Brites, Fernando

    2017-04-01

    Iron deficiency anemia (IDA) affects around 20-30% of adults worldwide. An association between IDA and cardiovascular disease (CVD) has been reported. Oxidative stress, inflammation and low concentration of high-density lipoproteins (HDL) were implicated on endothelial dysfunction and CVD in IDA. We studied the effects of iron deficiency and of an intravenous iron administration on oxidative stress and HDL characteristics in IDA women. Two studies in IDA women are presented: a case-control study, including 18 patients and 18 age-matched healthy women, and a follow-up study 72hr after the administration of intravenous iron (n = 16). Lipids, malondialdehyde, cholesteryl ester transfer protein (CETP), paraoxonase-1 (PON-1) and HDL chemical composition and functionality (cholesterol efflux and antioxidative activity) were measured. Cell cholesterol efflux from iron-deficient macrophages to a reference HDL was also evaluated. IDA patients showed higher triglycerides and CETP activity and lower HDL-C than controls (all p HDL particles from IDA patients showed higher triglyceride content (+30%,p HDL-mediated cholesterol efflux was similar between the patients and controls, iron deficiency provoked a significant reduction in macrophage cholesterol efflux (-25%,p HDL particles. It remains to be determined if such alterations suffice to impair endothelial function in IDA. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  9. The pharmacokinetics of sodium cromoglycate in man after intravenous and inhalation administration.

    Science.gov (United States)

    Neale, M G; Brown, K; Hodder, R W; Auty, R M

    1986-01-01

    The pharmacokinetics of sodium cromoglycate in four healthy volunteers after slow intravenous infusion have been evaluated following measurement of plasma concentrations by radioimmunoassay. The results confirm earlier findings that sodium cromoglycate is rapidly eliminated from the body and that the data can be fitted to a two compartment open model. The pharmacokinetic parameters derived from the intravenous administration were used to evaluate the pharmacokinetics after inhalation administration via the Spinhaler. A model for absorption from the lungs is described which involves absorption at two different rates; this gives a better fit to the observed data than a single absorption rate. A fast absorption rate constant with a mean value of 0.54 min-1 and a slower rate constant with a mean value of 0.0097 min-1 were found. Of a mean total of 2.84 mg absorbed from a 20 mg inhaled dose, 0.68 +/- 0.15 (s.e. mean) mg were absorbed at the fast rate and 2.17 +/- 0.37 mg at the slower rate. These rates probably reflect absorption from different sites within the lungs. The results may have important implications for interpretation of clinical findings. PMID:3094571

  10. Pharmacokinetics of buprenorphine following intravenous and buccal administration in cats, and effects on thermal threshold.

    Science.gov (United States)

    Hedges, A R; Pypendop, B H; Shilo-Benjamini, Y; Stanley, S D; Ilkiw, J E

    2014-06-01

    This study reports the pharmacokinetics of buprenorphine, following i.v. and buccal administration, and the relationship between buprenorphine concentration and its effect on thermal threshold. Buprenorphine (20 μg/kg) was administered intravenously or buccally to six cats. Thermal threshold was determined, and arterial blood sampled prior to, and at various times up to 24 h following drug administration. Plasma buprenorphine concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to the time-concentration data. Pharmacokinetic/pharmacodynamic models were fitted to the concentration-thermal threshold data. Thermal threshold was significantly higher than baseline 44 min after buccal administration, and 7, 24, and 104 min after i.v. administration. A two- and three-compartment model best fitted the data following buccal and i.v. administration, respectively. Following i.v. administration, mean ± SD volume of distribution at steady-state (L/kg), clearance (mL·min/kg), and terminal half-life (h) were 11.6 ± 8.5, 23.8 ± 3.5, and 9.8 ± 3.5. Following buccal administration, absorption half-life was 23.7 ± 9.1 min, and terminal half-life was 8.9 ± 4.9 h. An effect-compartment model with a simple effect maximum model best predicted the time-course of the effect of buprenorphine on thermal threshold. Median (range) ke0 and EC50 were 0.003 (0.002-0.018)/min and 0.599 (0.073-1.628) ng/mL (i.v.), and 0.017 (0.002-0.023)/min and 0.429 (0.144-0.556) ng/mL (buccal).

  11. Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses.

    Science.gov (United States)

    Knych, H K; Arthur, R M; Mitchell, M M; Holser, I; Poppenga, R; Smith, L L; Helm, M N; Sams, R A; Gaskill, C L

    2015-07-01

    Cobalt has been used by human athletes due to its purported performance-enhancing effects. It has been suggested that cobalt administration results in enhanced erythropoiesis, secondary to increased circulating erythropoietin (EPO) concentrations leading to improvements in athletic performance. Anecdotal reports of illicit administration of cobalt to horses for its suspected performance enhancing effects have led us to investigate the pharmacokinetics and pharmacodynamic effects of this compound when administered in horses, so as to better regulate its use. In the current study, 18 horses were administered a single intravenous dose of cobalt chloride or cobalt gluconate and serum and urine samples collected for up to 10 days post administration. Cobalt concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS) and pharmacokinetic parameters determined. Additional blood samples were collected for measurement of equine EPO concentrations as well as to assess any effects on red blood cell parameters. Horses were observed for adverse effects and heart rate monitored for the first 4 h post administration. Cobalt was characterized by a large volume of distribution (0.939 L/kg) and a prolonged gamma half-life (156.4 h). Cobalt serum concentrations were still above baseline values at 10 days post administration. A single administration of cobalt had no effect on EPO concentrations, red blood cell parameters or heart rate in any of the horses studied and no adverse effects were noted. Based on the prolonged gamma half-life and prolonged residence time, regulators should be able to detect administration of a single dose of cobalt to horses.

  12. Pharmacokinetics of spiramycin after intravenous, intramuscular and subcutaneous administration in lactating cows.

    Science.gov (United States)

    Sanders, P; Moulin, G; Guillot, P; Dagorn, M; Perjant, P; Delepine, B; Gaudiche, C; Mourot, D

    1992-03-01

    Spiramycin is a macrolide antibiotic that is active against most of the microorganisms isolated from the milk of mastitic cows. This work investigated the disposition of spiramycin in plasma and milk after intravenous, intramuscular and subcutaneous administration. Twelve healthy cows were given a single injection of spiramycin at a dose of 30,000 IU/kg by each route. Plasma and milk were collected post injection. Spiramycin concentration in the plasma was determined by a high performance liquid chromatography method, and in the milk by a microbiological method. The mean residence time after intravenous administration was significantly longer (P less than 0.01) in the milk (20.7 +/- 2.7 h) than in plasma (4.0 +/- 1.6 h). An average milk-to-plasma ratio of 36.5 +/- 15 was calculated from the area concentration-time curves. Several pharmacokinetic parameters were examined to determine the bioequivalence of the two extravascular routes. The dose fraction adsorbed after intramuscular or subcutaneous administration was almost 100% and was bioequivalent for the extravascular routes, but the rates of absorption, the maximal concentrations and the time to obtain them differed significantly between the two routes. Spiramycin quantities excreted in milk did not differ between the two extravascular routes but the latter were not bioequivalent for maximal concentration in the milk. However, the two routes were bio-equivalent for the duration of time the milk concentration exceeded the minimal inhibitory concentration (MIC) of various pathogens causing infections in the mammary gland.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta)

    Science.gov (United States)

    Kelly, Kristi R.; Pypendop, Bruno H.; Christe, Kari L.

    2014-01-01

    Recently, tramadol and its active metabolite, O-desmethyltramadol (M1), have been studied as analgesic agents in various traditional veterinary species (e.g. dogs, cats, etc.). This study explores the pharmacokinetics of tramadol and M1 after intravenous (IV) and oral (PO) administration in rhesus macaques (Macaca mulatta), a nontraditional veterinary species. Rhesus macaques are Old World monkeys that are commonly used in biomedical research. Effects of tramadol administration to monkeys are unknown, and research veterinarians may avoid inclusion of this drug into pain management programs due to this limited knowledge. Four healthy, socially-housed, adult male rhesus macaques (Macaca mulatta) were used in this study. Blood samples were collected prior to, and up to 10 h post tramadol administration. Serum tramadol and M1 were analyzed using liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed. Tramadol clearance was 24.5 (23.4-32.7) mL/min/kg. Terminal half-life of tramadol was 111 (106-127) min IV and 133 (84.9-198) min PO. Bioavailability of tramadol was poor [3.47% (2.14-5.96%)]. Maximum serum concentration of M1 was 2.28 (1.88-2.73) ng/mL IV and 11.2 (9.37-14.9) ng/mL PO. Sedation and pruritus were observed after IV administration (180 words). PMID:25488714

  14. Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Kelly, K R; Pypendop, B H; Christe, K L

    2015-08-01

    Recently, tramadol and its active metabolite, O-desmethyltramadol (M1), have been studied as analgesic agents in various traditional veterinary species (e.g., dogs, cats, etc.). This study explores the pharmacokinetics of tramadol and M1 after intravenous (IV) and oral (PO) administration in rhesus macaques (Macaca mulatta), a nontraditional veterinary species. Rhesus macaques are Old World monkeys that are commonly used in biomedical research. Effects of tramadol administration to monkeys are unknown, and research veterinarians may avoid inclusion of this drug into pain management programs due to this limited knowledge. Four healthy, socially housed, adult male rhesus macaques (Macaca mulatta) were used in this study. Blood samples were collected prior to, and up to 10 h post-tramadol administration. Serum tramadol and M1 were analyzed using liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed. Tramadol clearance was 24.5 (23.4-32.7) mL/min/kg. Terminal half-life of tramadol was 111 (106-127) min IV and 133 (84.9-198) min PO. Bioavailability of tramadol was poor [3.47% (2.14-5.96%)]. Maximum serum concentration of M1 was 2.28 (1.88-2.73) ng/mL IV and 11.2 (9.37-14.9) ng/mL PO. Sedation and pruritus were observed after IV administration.

  15. The effect of preoperative intravenous paracetamol administration on postoperative fever in pediatrics cardiac surgery.

    Science.gov (United States)

    Abdollahi, Mohammad-Hasan; Foruzan-Nia, Khalil; Behjati, Mostafa; Bagheri, Babak; Khanbabayi-Gol, Mehdi; Dareshiri, Shahla; Pishgahi, Alireza; Zarezadeh, Rafie; Lotfi-Naghsh, Nazgol; Lotfi-Naghsh, Ainaz; Naghavi-Behzad, Mohammad

    2014-09-01

    Post-operative fever is a common complication of cardiac operations, which is known to be correlated with a greater degree of cognitive dysfunction 6 weeks after cardiac surgery. The aim of the present study was to examine efficacy and safety of single dose intravenous Paracetamol in treatment of post-operative fever in children undergoing cardiac surgery. In this randomised, double-blind, placebo-controlled clinical trial, 80 children, aged 1-12 years, presenting for open heart surgery were entered in the trial and randomly allocated into two groups: Placebo and Paracetamol. After induction of anaesthesia, 15 mg/kg intravenous Paracetamol solution was infused during 1 h in the Paracetamol group. Patients in placebo group received 15 mg/kg normal saline infusion during the same time. Since the end of operation until next 24 h in intensive care unit, axillary temperature of the two group patients was recorded in 4-h intervals. Any fever that occurred during this period had been treated with Paracetamol suppository (125 mg) and the amount of antipyretic drug consumption for each patient had been recorded. In order to examine the safety of Paracetamol, patients were evaluated for drug complication at the same time. Mean axillary temperature during first 24 h after operation was significantly lower in Paracetamol group compared with placebo group (P = 0.001). Overall fever incidence during 24 h after operation was higher in placebo group compared with Paracetamol group (P = 0.012). Of Paracetamol group patients, 42.5% compared with 15% of placebo group participants had no consumption of antipyretic agent (Paracetamol suppository) during 24 h after operation (P = 0.001). This study suggests that single dose administration of intravenous Paracetamol before paediatric cardiac surgeries using cardiopulmonary bypass; reduce mean body temperature in the first 24 h after operation.

  16. Comparative pharmacokinetics of amoxicillin/clavulanic acid combination after intravenous administration to sheep and goats.

    Science.gov (United States)

    Carceles, C M; Escudero, E; Baggot, J D

    1995-04-01

    The pharmacokinetic behaviour of an amoxicillin/clavulanic acid combination was studied after intravenous administration of single doses (20 mg/kg per kg body weight) to five sheep and six goats. The objective was to determine whether there are differences between sheep and goats in the disposition of amoxicillin and clavulanic acid. The plasma concentration-time data were analysed by compartmental pharmacokinetic and non-compartmental methods. The disposition curves for both drugs were best described by a biexponential equation (two-compartment open model) in sheep and goats. The elimination half-lives of amoxicillin were 1.43 +/- 0.16 h in sheep and 1.13 +/- 0.19 h in goats, and of clavulanic acid were 1.16 +/- 0.01 h and 0.85 +/- 0.09 h in sheep and goats respectively. The apparent volumes of distribution of amoxicillin and clavulanic acid were similar in the two species. Body clearances of amoxicillin were 0.09 +/- 0.01 L/h kg in sheep and 0.11 +/- 0.01 L/h kg in goats, and of clavulanic acid were 0.07 +/- 0.01 L/h kg and 0.12 +/- 0.01 L/h kg in sheep and goats respectively. The half-lives and body clearances of amoxicillin and clavulanic acid differed significantly between sheep and goats. It was concluded that the disposition of amoxicillin and clavulanic acid administered intravenously as an amoxicillin/clavulanic acid combination to sheep and goats differed between the two ruminant species. Even though the differences in disposition kinetics of both drugs were statistically significant, the same intravenous dosing rate of this antimicrobial combination can generally be used in sheep and goats.

  17. The effect of preoperative intravenous paracetamol administration on postoperative fever in pediatrics cardiac surgery

    Directory of Open Access Journals (Sweden)

    Mohammad-Hasan Abdollahi

    2014-01-01

    Full Text Available Background: Post-operative fever is a common complication of cardiac operations, which is known to be correlated with a greater degree of cognitive dysfunction 6 weeks after cardiac surgery. The aim of the present study was to examine efficacy and safety of single dose intravenous Paracetamol in treatment of post-operative fever in children undergoing cardiac surgery. Materials and Methods: In this randomised, double-blind, placebo-controlled clinical trial, 80 children, aged 1-12 years, presenting for open heart surgery were entered in the trial and randomly allocated into two groups: Placebo and Paracetamol. After induction of anaesthesia, 15 mg/kg intravenous Paracetamol solution was infused during 1 h in the Paracetamol group. Patients in placebo group received 15 mg/kg normal saline infusion during the same time. Since the end of operation until next 24 h in intensive care unit, axillary temperature of the two group patients was recorded in 4-h intervals. Any fever that occurred during this period had been treated with Paracetamol suppository (125 mg and the amount of antipyretic drug consumption for each patient had been recorded. In order to examine the safety of Paracetamol, patients were evaluated for drug complication at the same time. Results: Mean axillary temperature during first 24 h after operation was significantly lower in Paracetamol group compared with placebo group (P = 0.001. Overall fever incidence during 24 h after operation was higher in placebo group compared with Paracetamol group (P = 0.012. Of Paracetamol group patients, 42.5% compared with 15% of placebo group participants had no consumption of antipyretic agent (Paracetamol suppository during 24 h after operation (P = 0.001. Conclusion: This study suggests that single dose administration of intravenous Paracetamol before paediatric cardiac surgeries using cardiopulmonary bypass; reduce mean body temperature in the first 24 h after operation.

  18. Development of novel docetaxel phospholipid nanoparticles for intravenous administration: quality by design approach.

    Science.gov (United States)

    Yadav, Dharmendra K; Pawar, Harish; Wankhade, Shrikant; Suresh, Sarasija

    2015-08-01

    The objective of this study was to develop novel docetaxel phospholipid nanoparticles (NDPNs) for intravenous administration. Modified solvent diffusion-evaporation method was adopted in the NDPN preparation. Central composite design (CCD) was employed in the optimization of the critical formulation factor (drug content) and process variable (stirring rate) to obtain NDPNs with 215.53 ± 1.9-nm particle size, 0.329 ± 0.02 polydispersity index (PDI), and 75.41 ± 4.81% entrapment efficiency. The morphological examination by transmission electron microscopy revealed spherical structure composed of a drug core stabilized within the phospholipid shell. Enhanced cell uptake of coumarin-6-loaded phospholipid nanoparticles by MCF-7 cell line indicated NDPN-efficient cell uptake. In vitro hemolysis test confirmed the safety of the phospholipid nanoparticles. NDPNs exhibited increased area under the curve (AUC) and mean residence time (MRT) by 3.0- and 3.3-fold, respectively, in comparison with the existing docetaxel parenteral formulation (Taxotere®), indicating a potential for sustained action. Thus, the novel NDPNs exhibit an ability to be an intravenous docetaxel formulation with enhanced uptake, decreased toxicity, and prolonged activity.

  19. Disposition kinetics of long acting moxifloxacin following intravenous administration in Sheep

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    Chirag M. Modi

    Full Text Available Aim: The objective of the present study was to study the disposition kinetics and dosage regimens of long acting moxifloxacin following intravenous administration at the dose rate of 7.5 mg/kg-1 b. wt. in six male sheep and to calculate dosage regimens of the same in sheep. Materials and Methods: The study was conducted using six healthy male sheep. Long acting Moxifloxacin solution (10 % moxifloxacin in solution with L- arginine, N-butyl alcohol and benzyl alcohol was injected in jugular vein and periodical blood samples were collected from contra-lateral jugular vein in test tubes containing 30-50 IU heparin (anticoagulant at 0.083 (5 min, 0.166 (10 min, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 60, 72 and up to 96 h post administration of drug. Drug concentration in plasma was determined using High Performance Liquid Chromatography (HPLC with Fluorescence Detector. The blood concentrations versus time data were analyzed using software. Results: After single dose intravenous administration of long acting moxifloxacin the plasma concentration of 0.016 ± 0.001 μg/ml-1 was maintained for up to 72 h. Distribution half-life (t and elimination half-life (t were 1.637 ± 0.053 h, and 1/2 1/2 12.130 ± 0.202 h, following IV administration. The mean values of apparent volume of distribution V 5.436 ± 0.135 L/kg-1 d(area as well as mean residence time 10.02 ± 4.787 minute were detected with IV administration. Conclusion: The long acting Moxifloxacin @ the dose 7.5 mg/kg IV maintains the effective therapeutic concentration in the plasma of sheep for up to 72 hours. The long acting Moxifloxacin at this dose rate can be used to treat sensitive bacteria causing infectious diseases in sheep. [Vet World 2012; 5(9.000: 517-521

  20. [Administration of intravenous immunoglobulins in neurology. An evidence-based consensus: update 2010].

    Science.gov (United States)

    Stangel, M; Gold, R

    2011-04-01

    Our knowledge on the clinical efficacy of intravenous immunoglobulins (IVIg) in neurological diseases has greatly increased in the last 5 years. Liquid formulations with a higher concentration of IVIg have simplified administration. Despite a worldwide increase in plasma production it is still a valuable biological product which is why current indications must be continuously validated. Long-term efficacy of the preparation Gamunex could be demonstrated in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). In acute myasthenic worsening a dose of 1 g IVIg/kg body weight appears to be sufficient for clinical stabilization. New indications, such as the postpolio syndrome or Alzheimer's disease are being explored in clinical trials. In addition to the consensus statement from 2004 the evidence for clinical use of IVIg has been re-evaluated and recommendations are given.

  1. INTRAVENOUS IMMUNOGLOBULIN ADMINISTRATION FOR DESENSITIZATION BEFORE RENAL TRANSPLANTATION AND MANAGING ANTIBODY-MEDIATED REJECTION

    Directory of Open Access Journals (Sweden)

    A. I. Sushkov

    2011-01-01

    Full Text Available Much attention has been placed recently in transplantation in highly HLA-sensitized patients. In attempts to remove these antibodies and enable successful renal transplantation, several approaches have been developed. Intravenous immunoglobulin (IVIG was found to be effective in the treatment of autoimmune and inflammatory disorders (e. g. Kawasaki disease, Guillain-Barre syndrome. Recently, a beneficial effect of IVIG on the reduc- tion of anti-HLA antibodies was described. The anti-inflammatory effect of IVIG provides hopeful opportunities in antibody-mediated rejection (AMR management. There are several protocols of IVIG administration for pre-transplant desensitization and AMR treatment: high-dose IVIG, low-dose IVIG + plasmapheresis, IVIG + plasmapheresis + rituximab. These advancements have enabled transplantation in patients previously considered untransplantable and in concert with new diagnostic techniques has resulted in new approaches to management of AMR. 

  2. Pharmacokinetics of a florfenicol-tylosin combination after intravenous and intramuscular administration to beagle dogs.

    Science.gov (United States)

    Kim, Eun-Young; Gebru, Elias; Lee, Joong-Su; Kim, Jong-Choon; Park, Seung-Chun

    2011-04-01

    A pharmacokinetic study of a commercial florfenicol-tylosin (2:1) combination product was conducted in six beagle dogs after intravenous (IV) and intramuscular (IM) administration at doses of 10 mg/kg (florfenicol) and 5 mg/kg (tylosin). Serum drug concentrations were determined by a validated high performance liquid chromatography (HPLC) using UV detection. A rapid and nearly complete absorption of both drugs with a mean IM bioavailability of 103.9% (florfenicol) and 92.6% (tylosin), prolonged elimination half-life, and high tissue penetration with steady state volume of distribution of 2.63 l/kg (florfenicol) and 1.98 l/kg (tylosin) were observed. Additional studies, including pharmacodynamic and toxicological evaluation are required before recommendations can be made regarding the clinical application of the product in dogs.

  3. Intravenous or oral administration of vinorelbine in adjuvant chemotherapy with cisplatin and vinorelbine for resected NSCLC

    DEFF Research Database (Denmark)

    Sorensen, Steffen Filskov; Carus, Andreas; Meldgaard, Peter

    2015-01-01

    OBJECTIVES: Cisplatin and vinorelbine given intravenously is a well-established adjuvant chemotherapy regimen after surgery for early-stage NSCLC. Vinorelbine can also be administered orally. However, the efficacy of orally administrated vinorelbine in adjuvant treatment of NSCLC is unknown. We...... assessed the overall survival (OS) and disease-free survival (DFS) of patients treated with adjuvant i.v. vinorelbine or p.o. vinorelbine, in combination with i.v. cisplatin. MATERIALS AND METHODS: We reviewed two time-separated cohorts of patients referred to the Department of Oncology at Aarhus...... University Hospital (Denmark) from 2005 to 2012 for adjuvant chemotherapy after surgery for NSCLC. RESULTS AND CONCLUSION: Of the 265 patients included in this study, 126 patients received i.v. and 139 received p.o. vinorelbine/cisplatin. The two groups were comparable with respect to important baseline...

  4. Mitotherapy for Fatty Liver by Intravenous Administration of Exogenous Mitochondria in Male Mice.

    Science.gov (United States)

    Fu, Ailing; Shi, Xianxun; Zhang, Huajing; Fu, Bin

    2017-01-01

    Mitochondrial dysfunction is a major and common mechanism in developing non-alcoholic fatty liver disease (NAFLD). Replacement of dysfunctional mitochondria by functional exogenous mitochondria may attenuate intrahepatic excessive lipid and recover hepatocyte function. However, no data shows that mitochondria can be systemically administrated to animals to date. Here we suggest that mitochondria isolated from hepatoma cells are used as a mitotherapy agent to treat mouse fatty liver induced by high-fat diets. When the mitochondria were intravenously injected into the mice, serum aminotransferase activity and cholesterol level decreased in a dose-dependent manner. Also, the mitotherapy reduced lipid accumulation and oxidation injury of the fatty liver mice, improved energy production, and consequently restored hepatocyte function. The mitotherapy strategy offers a new potential therapeutic approach for treating NAFLD.

  5. Disposition of marbofloxacin in vulture (Gyps fulvus) after intravenous administration of a single dose.

    Science.gov (United States)

    Garcia-Montijano, Marino; Waxman, Samanta; de Lucas, J Julio; Luaces, I; de San Andrés, María Dolores; Rodríguez, Casilda

    2011-04-01

    The pharmacokinetics properties of marbofloxacin were studied in adult Eurassian Griffon vulture after single-dose intravenous (IV) administration of 2mg/kg. Drug concentration in plasma was determined by high-performance liquid chromatography and the data obtained were subjected to compartmental and non-compartmental kinetic analysis. Marbofloxacin presented a volume of distribution at steady-state (Vdss) of 1.51±0.22L and total plasma clearance (Cl) of 0.109±0.023L/hkg. The permanence of this drug was long in vultures (T(1/2)(λ)=12.51±2.52h; MRT(∞)=13.54±2.29h). The optimal dose of marbofloxacin estimated is 2.73mg/kg per day for the treatment of infections in vultures with MIC(90)=0.2μg/mL.

  6. Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration.

    Science.gov (United States)

    Zeng, Xiao-yan; Dong, Shu; He, Nan-nan; Jiang, Chun-jie; Dai, Yue; Xia, Yu-feng

    2015-09-01

    Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, Cmax and AUC(0-10h) values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the Cmax and AUC(0-10h) values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines.

  7. Major vessel occlusion may predict subtherapeutic anticoagulation intensity and feasibility of administration of intravenous thrombolytics

    Science.gov (United States)

    Chang, Jun Young; Jung, Seunguk; Park, Hyun

    2017-01-01

    Objective We investigated the association between the presence of major vessel occlusion (MVO) and the intensity of the International Normalized Ratio (INR) in cardioembolic high-risk patients taking warfarin. We also evaluated whether the presence of MVO could predict the subtherapeutic range of INR ≤1.7 ensuring safe administration of intravenous thrombolytics. Methods The medical records of 177 cardioembolic stroke patients who were taking warfarin between April, 2008 and March, 2015 were retrospectively analyzed. Logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between vessel occlusion and intensity of INR. To predict INR ≤1.7, decision tree analysis was performed. Results INR was inversely associated with MVO in an unadjusted model (OR, 0.36; 95% CI, 0.17–0.76), and in a model adjusted for initial NIHSS score and time from symptom onset to arrival (OR, 0.28; 95% CI, 0.11–0.73). Fifty-two of 58 (89.7%) patients with MVO had an INR ≤1.7, compared with 83 of 119 (69.7%) patients without MVO. Indication for anticoagulation agent use was dichotomized into NVAF and others, and applied to the subgroup of patients with MVO. All patients with NVAF (31/31, 100%) had INR ≤1.7, while 21 of 27 of the other patients (77.8%) had INR ≤1.7. Conclusions Low INR at presentation in cardioembolic stroke patients during anticoagulation treatment was associated with occurrence of major vessel occlusive stroke. Presence of MVO and indications for anticoagulation may be utilized to ensure the feasibility of administration of intravenous thrombolytics. PMID:28158211

  8. Pharmacokinetic study of salvianolic acid D after oral and intravenous administration in rats.

    Science.gov (United States)

    Song, Junke; Zhang, Wen; Sun, Jialin; Xu, Xiaona; Zhang, Xue; Zhang, Li; Feng, Zhangying; Du, Guan-Hua

    2015-05-01

    A sensitive, specific and rapid LC-MS method was developed and validated for the determination of salvianolic acid D (SalD) in rat plasma. This method used a single quadrupole mass spectrometer with an electrospray ionization (ESI) source. A single ion monitoring scanning (SIM) mode was employed. It showed good linearity over the concentration range from 3.3 to 666.7 ng/mL for the determination of SalD. The R.S.D.% of intra-day and inter-day precision values were no more than 7.69%, and the accuracy was within 91%-104% at all quality control levels. This LC-MS method was applied to the pharmacokinetic study of SalD in rats. A two-compartmental model analysis was employed. The plasma concentrations at 2 min (C 2min) were 5756.06±719.61, 11,073.01±1783.46 and 21,077.58±5581.97 μg/L for 0.25, 0.5 and 1 mg/kg intravenous injection, respectively. The peak plasma concentration (C max) was 333.08±61.21 μg/L for 4 mg/kg oral administration. The area under curve (AUC0-t ) was 14,384.379±8443.184, 22,813.369±11,860.823, 46,406.122±27,592.645 and 8201.740±4711.961 μg/L·h for intravenous injection (0.25, 0.5 and 1 mg/kg) and oral administration (4 mg/kg), respectively. The bioavailability of SalD was calculated to be 4.159%±0.517%.

  9. Some pharmacokinetic parameters of ampicillin/sulbactam combination after intravenous and intramuscular administration to goats.

    Science.gov (United States)

    Espuny, A; Carceles, C M; Vicente, M S; Escudero, E

    1996-12-01

    Some pharmacokinetic parameters of an ampicillin/sulbactam (2:1) combination were studied in six goats, after intravenous and intramuscular injection at a single dosage of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam). The drugs were distributed according to an open two-compartment model. The apparent volumes of distribution calculated by the area method of ampicillin and sulbactam were 0.34 +/- 0.04 l/kg and 0.45 +/- 0.15 l/kg, respectively, and the total body clearances were 0.72 +/- 0.11 and 0.38 +/- 0.07 l/kg.h. The half-lives of ampicillin after intravenous and intramuscular administration were 0.32 +/- 0.04 h and 0.71 +/- 0.14 h, respectively. For sulbactam the half-lives were 0.79 +/- 0.18 h and 1.13 +/- 0.21 h after administration by the same routes. The bioavailability after intramuscular injection was high and similar for both drugs (98.29% for ampicillin and 101.84% for sulbactam). The mean peak plasma levels of ampicillin (0.43 +/- 0.27 h) and sulbactam (0.34 +/- 0.14 h) were reached at a similar time, and peak concentrations were also similar and non-proportional to the dose of the products administered (11.02 +/- 3.11 mg/l of ampicillin and 9.5 +/- 0.98 mg/l of sulbactam).

  10. Pharmacokinetic study of salvianolic acid D after oral and intravenous administration in rats

    Science.gov (United States)

    Song, Junke; Zhang, Wen; Sun, Jialin; Xu, Xiaona; Zhang, Xue; Zhang, Li; Feng, Zhangying; Du, Guan-hua

    2015-01-01

    A sensitive, specific and rapid LC-MS method was developed and validated for the determination of salvianolic acid D (SalD) in rat plasma. This method used a single quadrupole mass spectrometer with an electrospray ionization (ESI) source. A single ion monitoring scanning (SIM) mode was employed. It showed good linearity over the concentration range from 3.3 to 666.7 ng/mL for the determination of SalD. The R.S.D.% of intra-day and inter-day precision values were no more than 7.69%, and the accuracy was within 91%−104% at all quality control levels. This LC-MS method was applied to the pharmacokinetic study of SalD in rats. A two-compartmental model analysis was employed. The plasma concentrations at 2 min (C2min) were 5756.06±719.61, 11,073.01±1783.46 and 21,077.58±5581.97 μg/L for 0.25, 0.5 and 1 mg/kg intravenous injection, respectively. The peak plasma concentration (Cmax) was 333.08±61.21 μg/L for 4 mg/kg oral administration. The area under curve (AUC0−t) was 14,384.379±8443.184, 22,813.369±11,860.823, 46,406.122±27,592.645 and 8201.740±4711.961 μg/L·h for intravenous injection (0.25, 0.5 and 1 mg/kg) and oral administration (4 mg/kg), respectively. The bioavailability of SalD was calculated to be 4.159%±0.517%. PMID:26579453

  11. Pharmacokinetic study of salvianolic acid D after oral and intravenous administration in rats

    Directory of Open Access Journals (Sweden)

    Junke Song

    2015-05-01

    Full Text Available A sensitive, specific and rapid LC-MS method was developed and validated for the determination of salvianolic acid D (SalD in rat plasma. This method used a single quadrupole mass spectrometer with an electrospray ionization (ESI source. A single ion monitoring scanning (SIM mode was employed. It showed good linearity over the concentration range from 3.3 to 666.7 ng/mL for the determination of SalD. The R.S.D.% of intra-day and inter-day precision values were no more than 7.69%, and the accuracy was within 91%−104% at all quality control levels. This LC-MS method was applied to the pharmacokinetic study of SalD in rats. A two-compartmental model analysis was employed. The plasma concentrations at 2 min (C2min were 5756.06±719.61, 11,073.01±1783.46 and 21,077.58±5581.97 μg/L for 0.25, 0.5 and 1 mg/kg intravenous injection, respectively. The peak plasma concentration (Cmax was 333.08±61.21 μg/L for 4 mg/kg oral administration. The area under curve (AUC0−t was 14,384.379±8443.184, 22,813.369±11,860.823, 46,406.122±27,592.645 and 8201.740±4711.961 μg/L·h for intravenous injection (0.25, 0.5 and 1 mg/kg and oral administration (4 mg/kg, respectively. The bioavailability of SalD was calculated to be 4.159%±0.517%.

  12. Biodistribution of colloidal gold nanoparticles after intravenous administration: effect of particle size.

    Science.gov (United States)

    Sonavane, Ganeshchandra; Tomoda, Keishiro; Makino, Kimiko

    2008-10-15

    Purpose of the present research work was to evaluate the biological distribution of differently size gold nanoparticles (NP) up on intravenous administration in mice. Another objective was to study effect of particle size on biological distribution of gold NP to enable their diverse applications in nanotechnology. Gold NP of different particle sizes, mainly 15, 50, 100 and 200 nm, were synthesized by modifying citrate ion concentration. Synthesized gold nanoparticles were characterized by SEM and their size distribution was studied by particle size analyzer. Gold NP was suspended in sodium alginate solution (0.5%, w/v) and administered to mice (1g/kg, intravenously) [n=3]. After 24h of administration of gold NP, blood was collected under light ether anesthesia, mice were sacrificed by cervical dislocation and various tissues/organs were removed. The tissues were then washed with saline, homogenized and lysed with aqua regia. The determination of gold in samples was carried out quantitatively by inductively coupled plasma mass spectrometry (ICP-MS). SEM study revealed spherical morphology of gold NP with narrow particle size distribution. Biodistribution study revealed gold NPs of all sizes were mainly accumulated in organs like liver, lung and spleen. The accumulation of gold NP in various tissues was found to be depending on particle size. 15 nm gold NP revealed higher amount of gold and number of particles in all the tissues including blood, liver, lung, spleen, kidney, brain, heart, stomach. Interestingly, 15 and 50 nm gold NP were able to pass blood-brain barrier as evident from gold concentration in brain. Two-hundred nanometers gold NP showed very minute presence in organs including blood, brain, stomach and pancreas. The results revealed that tissue distribution of gold nanoparticles is size-dependent with the smallest 15 nm nanoparticles showing the most widespread organ distribution.

  13. Prehospital Medication Administration: A Randomised Study Comparing Intranasal and Intravenous Routes

    Directory of Open Access Journals (Sweden)

    Cian McDermott

    2012-01-01

    Full Text Available Introduction. Opioid overdose is an ever-increasing problem globally. Recent studies have demonstrated that intranasal (IN naloxone is a safe and effective alternative to traditional routes of naloxone administration for reversal of opioid overdose. Aims. This randomised controlled trial aimed to compare the time taken to deliver intranasal medication with that of intravenous (IV medication by advanced paramedic trainees. Methods. 18 advanced paramedic trainees administered either an IN or IV medication to a mannequin model in a classroom-based setting. The time taken for medication delivery was compared. End-user satisfaction was assessed using a 5-point questionnaire regarding ease of use and safety for both routes. Results. The mean time taken for the IN and IV group was 87.1 seconds and 178.2 seconds respectively. The difference in mean time taken was 91.1 seconds (95% confidence interval 55.2 seconds to 126.9 seconds, P≤0.0001. 89% of advanced paramedic trainees reported that the IN route was easier and safer to use than the IV route. Conclusion. This study demonstrates that, amongst advanced paramedic trainees, the IN route of medication administration is significantly faster, better accepted and perceived to be safer than using the IV route. Thus, IN medication administration could be considered more frequently when administering emergency medications in a pre-hospital setting.

  14. Pharmacokinetics of marbofloxacin in rabbit after intravenous, intramuscular, and subcutaneous administration.

    Science.gov (United States)

    Marín, P; Alamo, L F; Escudero, E; Fernández-Varón, E; Hernandis, V; Cárceles, C M

    2013-06-01

    The disposition kinetics of marbofloxacin, a fluoroquinolone antibiotic, after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration was determined in rabbits at a single dose of 2 mg/kg. Plasma concentrations of marbofloxacin were determined by high performance liquid chromatography with fluorescence detection. The concentration-time data were analysed by compartmental and non-compartmental pharmacokinetic methods. Steady-state volume of distribution (V(ss)) and clearance (Cl) of marbofloxacin after i.v. administration were 1.99±0.27 L/kg and 0.42±0.04 L/h kg, respectively. Following i.m. and s.c. administration marbofloxacin achieved maximum plasma concentrations of 2.04±0.32 and 1.64±0.15 mg/L at 0.33±0.16 and 0.50±0.18 h, respectively. The absolute bioavailabilities after i.m. and s.c. routes were 123.30±17.64% and 114.81±12.11%, respectively. From these data (kinetic parameters and absence of adverse reactions) marbofloxacin is likely to be effective in rabbits.

  15. Metabolic disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and skin administration in rats.

    Science.gov (United States)

    Fediuk, Daryl J; Wang, Tao; Chen, Yufei; Parkinson, Fiona E; Namaka, Michael P; Simons, Keith J; Burczynski, Frank J; Gu, Xiaochen

    2012-01-01

    Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone have shown a synergistic percutaneous enhancement when applied concurrently. Both compounds are extensively metabolized in vivo into a series of potentially toxic metabolites: 2 metabolites of DEET, N,N-diethyl-m-hydroxymethylbenzamide (DHMB) and N-ethyl-m-toluamide (ET), and 3 metabolites of oxybenzone, 2,4-dihydroxybenzophenone (DHB), 2,2-dihydroxy-4-methoxybenzophenone (DMB), and 2,3,4-trihydroxybenzophenone (THB). In this study, the metabolites were extensively distributed following intravenous and topical skin administration of DEET and oxybenzone in rats. Combined application enhanced the disposition of all DEET metabolites in the liver but did not consistently affect the distribution of oxybenzone metabolites. The DHMB appeared to be the major metabolite for DEET, while THB and its precursor DHB were the main metabolites for oxybenzone. Repeated once-daily topical application for 30 days led to higher concentrations of DEET metabolites in the liver. Hepatoma cell studies revealed a decrease in cellular proliferation from all metabolites as single and combined treatments, most notably at 72 hours. Increased accumulation of DHMB and ET in the liver together with an ability to reduce cellular proliferation at achievable plasma concentrations indicated that simultaneous exposure to DEET and oxybenzone might have the potential to precipitate adverse effects in a rat animal model.

  16. Pharmacokinetics of flunixin meglumine in mature swine after intravenous, intramuscular and oral administration.

    Science.gov (United States)

    Pairis-Garcia, Monique D; Karriker, Locke A; Johnson, Anna K; Kukanich, Butch; Wulf, Larry; Sander, Suzanne; Millman, Suzanne T; Stalder, Kenneth J; Coetzee, Johann F

    2013-08-13

    The purpose of this study was to determine intravenous (IV), intramuscular (IM) and oral (PO) FM PK in mature swine. Appropriate pain management for lameness in swine is a critical control point for veterinarians and producers, but science-based guidance on optimal housing, management and treatment of lameness is deficient. Six mature swine (121-168 kg) were administered an IV, IM, or PO dose of flunixin meglumine at a target dose of 2.2 mg/kg in a cross-over design with a 10 day washout period between treatments. Plasma samples collected up to 48 hours post-administration were analyzed by high pressure liquid chromatography and mass spectrometry (HPLC-MS) followed by non-compartmental pharmacokinetic analysis. No adverse effects were observed with flunixin meglumine administration for all routes. Flunixin meglumine was administered at an actual mean dose of 2.21 mg/kg (range: 2.05-2.48 mg/kg) IV, IM and PO. A mean peak plasma concentration (CMAX) for IM and PO administration was 3748 ng/ml (range: 2749-6004 ng/ml) and 946 ng/ml (range: 554-1593 ng/ml), respectively. TMAX was recorded at 1.00 hour (range: 0.50-2.00 hours) and 0.61 hours (range: 0.17-2.00 hours) after PO and IM administration. Half-life (T ½ λz) for IV, IM and PO administration was 6.29 hours (range: 4.84-8.34 hours), 7.49 hours (range: 5.55-12.98 hours) and 7.08 hours (range: 5.29-9.15 hours) respectively. In comparison, bioavailability (F) for PO administration was 22% (range: 11-44%) compared to IM F at 76% (range: 54-92%). The results of the present study suggest that FM oral administration is not the most effective administration route for mature swine when compared to IV and IM. Lower F and Cmax of PO-FM in comparison to IM-FM suggest that PO-FM is less likely to be an effective therapeutic administration route.

  17. Pharmacokinetics and Pharmacodynamic Effects of Flunixin after Intravenous, Intramuscular and Oral Administration to Dairy Goats

    Directory of Open Access Journals (Sweden)

    Odensvik K

    2003-12-01

    Full Text Available The pharmacokinetics and the prostaglandin (PG synthesis inhibiting effect of flunixin were determined in 6 Norwegian dairy goats. The dose was 2.2 mg/kg body weight administered by intravenous (i.v., intramuscular (i.m. and oral (p.o. routes using a cross-over design. Plasma flunixin content was analysed by use of liquid chromatography and the PG synthesis was evaluated by measuring plasma 15-ketodihydro-PGF2α by a radioimmuno-assay. Results are presented as median (range. The elimination half-lives (t1/2·λ were 3.6 (2.0–5.0, 3.4 (2.6–6.8 and 4.3 (3.4–6.1 h for i.v., i.m. and p.o. administration, respectively. Volume of distribution at steady state (Vdss was 0.35 (0.23–0.41 L/kg and clearance (CL, 110 (60–160 mL/h/kg. The plasma concentrations after oral administration showed a double-peak phenomenon with the two peaks occurring at 0.37 (0.25–1 and 3.5 (2.5–5.0 h, respectively. Both peaks were in the same order of magnitude. Bioavailability was 79 (53–112 and 58 (35%–120% for i.m. and p.o. administration, respectively. 15-Ketodihydro-PGF2α plasma concentrations decreased after flunixin administration independent of the route of administration.

  18. Pharmacokinetics of ketorolac tromethamine in horses after intravenous, intramuscular, and oral single-dose administration.

    Science.gov (United States)

    Bianco, A W; Constable, P D; Cooper, B R; Taylor, S D

    2016-04-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are an integral component of equine analgesia, yet currently available NSAIDs are both limited in their analgesic efficacy and have adverse effects. The NSAID ketorolac tromethamine (KT) is widely used in humans as a potent morphine-sparing analgesic drug but has not been fully evaluated in horses. The purpose of this study was to determine the pharmacokinetic profile of KT in horses after intravenous (i.v.), intramuscular (i.m.), and oral (p.o.) administration. Nine healthy adult horses received a single 0.5-mg/kg dose of KT via each route of administration. Plasma was collected up to 48 h postadministration and analyzed for KT concentration using HPLC/MS/MS. Noncompartmental analysis of i.v. dosage indicated a mean plasma clearance of 8.4 (mL/min)/kg and an estimated mean volume of distribution at steady-state of 0.77 L/kg. Noncompartmental analysis of i.v., i.m., and p.o. dosages indicated mean residence times of 2.0, 2.6, and 7.1 h, respectively. The drug was rapidly absorbed after i.m. and p.o. administration, and mean bioavailability was 71% and 57% for i.m. and p.o. administration, respectively. Adverse effects were not observed after i.v., i.m., and p.o. administration. More studies are needed to evaluate the analgesic and anti-inflammatory properties of KT in horses.

  19. Clinical pharmacokinetics of norfloxacin-glycine acetate after intravenous and oral administration in pigs

    Science.gov (United States)

    Chang, Zhi-Qiang; Oh, Byung-Chol; Kim, Jong-Choon; Jeong, Kyu-Shik; Lee, Myung-Heon; Yun, Hyo-In; Hwang, Mi-Hyun

    2007-01-01

    The pharmacokinetics and dosage regimen of norfloxacin-glycine acetate (NFLXGA) was investigated in pigs after a single intravenous (i.v.) or oral (p.o.) administration at a dosage of 7.2 mg/kg body weight. After both i.v. and p.o. administration, plasma drug concentrations were best fitted to an open two-compartment model with a rapid distribution phase. After i.v. administration of NFLXGA, the distribution (t1/2α) and elimination half-life (t1/2β) were 0.36 ± 0.07 h and 7.42 ± 3.55 h, respectively. The volume of distribution of NFLXGA at steady state (Vdss) was 4.66 ± 1.39 l/kg. After p.o. administration of NFLXGA, the maximal absorption concentration (Cmax) was 0.43 ± 0.06 µg/ml at 1.36 ± 0.39 h (Tmax). The mean absorption (t1/2ka) and elimination half-life (t1/2β) of NFLXGA were 0.78 ± 0.27 h and 7.13 ± 1.41 h, respectively. The mean systemic bioavailability (F) after p.o. administration was 31.10 ± 15.16%. We suggest that the optimal dosage calculated from the pharmacokinetic parameters is 5.01 mg/kg per day i.v. or 16.12 mg/kg per day p.o. PMID:17993748

  20. Amelioration of early radiation effects in oral mucosa (mouse) by intravenous or subcutaneous administration of amifostine

    Energy Technology Data Exchange (ETDEWEB)

    Fleischer, G. [Dept. of Radiotherapy and Radiooncology, Medical Faculty Carl Gustav Carus, Technical Univ., Dresden (Germany); Doerr, W. [Dept. of Radiotherapy and Radiooncology, Medical Faculty Carl Gustav Carus, Technical Univ., Dresden (Germany); Experimental Center, Medical Faculty Carl Gustav Carus, Technical Univ., Dresden (Germany)

    2006-10-15

    Purpose: to quantify the reduction of radiation-induced oral mucositis by amifostine as a function of administration route. Material and methods: mucosal ulceration of lower mouse tongue epithelium was analyzed. Amifostine was injected at 1.8 mg/injection subcutaneously (s.c.) or intravenously (i.v.), 45 min or 10 min prior to irradiation. With single-dose irradiation, a single amifostine injection was given. During daily fractionated irradiation (5 x 3 Gy) for 1 week, amifostine was administered s.c. or i.v. twice (days 0, 3), or s.c. on all irradiation days (days 0-4). With ten fractions over 2 weeks, five s.c. injections were given in week 1 (days 0-4) or week 2 (days 7-11), or both. Two i.v. injections were given either in week 1 (days 0, 3) or week 2 (days 7, 10). All fractionation protocols were terminated by graded test doses to generate full dose-effect curves. Results: in a single-dose control experiment, the ED{sub 50} (dose after which ulcer induction is expected in 50% of the mice) was 11.7 {+-} 1.4 Gy. Intravenous application of amifostine increased the ED{sub 50} to 14.0 {+-} 1.4 Gy (p = 0.024), while s.c. administration had no significant effect. The ED{sub 50} for test irradiation after 5 x 3 Gy was 5.8 {+-} 1.4 Gy. Two s.c. or i.v. amifostine injections yielded ED{sub 50} values of 7.2 {+-} 1.1 Gy (p = 0.0984) or 7.6 {+-} 1.2 Gy (p = 0.0334); five s.c. injections increased the ED{sub 50} to 8.2 {+-} 0.9 Gy (p = 0.0039). The ED{sub 50} after 10 x 3 Gy/2 weeks was 6.6 {+-} 1.8 Gy. Subcutaneous or intravenous administration of amifostine in week 1 yielded a significant increase in ED{sub 50} to 9.4 {+-} 2.5 Gy (p = 0.0099) and 10.0 {+-} 2.2 Gy (p = 0.0014). By contrast, amifostine administration in week 2 had no significant effect. Administration in weeks 1 and 2 resulted in an ED{sub 50} of 10.8 {+-} 3.6 Gy (p= 0.0053). Conclusion: amifostine during daily fractionated irradiation is effective only if administered in the initial treatment phase, i

  1. Michaelis-Menten elimination kinetics of etanercept, rheumatoid arthritis biologics, after intravenous and subcutaneous administration in rats.

    Science.gov (United States)

    Lee, Byung-Yo; Kwon, Kwang-Il; Kim, Min-Soo; Baek, In-Hwan

    2016-08-01

    Etanercept was approved by the Food and Drug Administration (FDA) in 2010 as a biologic agent for the treatment of rheumatoid arthritis (RA). The aim of the study was to investigate the pharmacokinetic properties of etanercept after intravenous and subcutaneous injection in rats. The plasma concentration of etanercept was determined using an enzyme-linked immunosorbent assay (ELISA). Intravenous and subcutaneous administration of 2 mg/kg of etanercept to rats showed that etanercept was slowly absorbed (time to reach the peak drug concentration [T max] = 1.60 days, bioavailability [F] = 47.18 %) and slowly eliminated (half-life [t 1/2], 2.33 days after intravenous administration and 3.31 days after subcutaneous administration). The area under the curve values on day 13 (AUC13day) were 121.25 ± 14.37 and 48.56 ± 6.78 μg day/mL after intravenous and subcutaneous administration, respectively. A two-compartment model with Michaelis-Menten elimination kinetics (V max = 94.28 µg/day; K m = 10.88 µg/mL) was used to describe the pharmacokinetic profile of etanercept. Our results describe the pharmacokinetic profile of etanercept, and these results could be used for the development of etanercept biosimilars.

  2. Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats.

    Science.gov (United States)

    Miller, M L; Aarde, S M; Moreno, A Y; Creehan, K M; Janda, K D; Taffe, M A

    2015-08-01

    d-Methamphetamine (METH) addiction is a serious public health concern for which successful treatment remains elusive. Immunopharmacotherapy has been shown to attenuate locomotor and thermoregulatory effects of METH. The current study investigated whether active vaccination against METH could alter intravenous METH self-administration in rats. Male Sprague-Dawley rats (Experiment 1: N=24; Experiment 2: N=18) were vaccinated with either a control keyhole-limpet hemocyanin conjugate vaccine (KLH) or a candidate anti-METH vaccine (MH6-KLH) or. Effects of vaccination on the acquisition of METH self-administration under two dose conditions (0.05, 0.1mg/kg/inf) and post-acquisition dose-substitution (0, 0.01, 0.05, 0.20mg/kg/inf, Experiment 1; 0.01, 0.05, 0.10, 0.15mg/kg/inf, Experiment 2) during steady-state responding were investigated. Plasma METH concentrations were determined 30min after an acute challenge dose of 3.2mg/kg METH. Active vaccination inhibited the acquisition of METH self-administration under the 0.1mg/kg/inf dose condition, with 66% of the MH6-KLH-vaccinated rats compared to 100% of the controls reaching criteria, and produced transient and dose-dependent effects on self-administration during the maintenance phase. Under the 0.05mg/kg/inf dose condition, MH6-KLH-vaccinated rats initially self-administered more METH than controls, but then self-administration decreased across the acquisition phase relative to controls; a subsequent dose-response assessment confirmed that MH6-KLH-vaccinated rats failed to acquire METH self-administration. Finally, plasma METH concentrations were higher in MH6-KLH-vaccinated rats compared to controls after an acute METH challenge, and these were positively correlated with antibody titers. These data demonstrate that active immunopharmacotherapy for METH attenuates the acquisition of METH self-administration. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Diuresis by intravenous administration of xanthurenic acid in rats, and inhibition by probenecid.

    Science.gov (United States)

    Uwai, Yuichi; Nakashima, Yuta; Honjo, Emi; Kawasaki, Tatsuya; Nabekura, Tomohiro

    2014-01-01

    The conjugates with sulfate and glucoside of xanthurenic acid, a tryptophan metabolite, were reported to show natriuresis. Sulfotransferase for xanthurenic acid works in the renal proximal tubule to produce the sulfate of xanthurenic acid as well as the liver, and we recently found that xanthurenic acid is a substrate of renal organic anion transporter OAT1. The purpose of this study was to examine relationship between the transport by OAT1 and diuresis related with xanthurenic acid. Drug transport experiment using Xenopus laevis oocytes represented that probenecid inhibited xanthurenic acid uptake by rat OAT1 (rOAT1). Although no diuresis was recognized by the intravenous injection of xanthurenic acid as a bolus in rats, the addition of its infusion exhibited natriuresis. Simultaneous administration of probenecid significantly decreased the urine volume and excreted amounts of sodium into urine. These findings showed the diuresis by the xanthurenic acid administration, and it was probenecid-sensitive. The rOAT1-mediated transport of xanthurenic acid might, at least in part, contribute to its diuretic effect.

  4. Intravenous administration of puppy deciduous teeth stem cells in degenerative valve disease

    Directory of Open Access Journals (Sweden)

    Soontaree Petchdee

    2016-12-01

    Full Text Available Aim: The objective of this study is to investigate the improvement of heart function in dogs with chronic valvular heart disease after puppy deciduous teeth stem cells (pDSCs administration. Materials and Methods: 20 client-owned dogs with degenerative valvular heart disease underwent multiple intravenous injections of allogeneic pDSCs. Dogs were randomly assigned to two groups: (i Control group (n=10 with standard treatment for heart failure and (ii group with standard treatment and multiple administrations of pDSCs (n=10. Electrocardiography, complete transthoracic echocardiography, thoracic radiography, and blood pressure were recorded before and after pDSCs injections for 15, 30 and 60 days. Results: Post pDSCs injection showed measurable improvement in left ventricular ejection fraction, American College of Veterinary Internal Medicine (ACVIM functional class significantly improved and improved quality of life scores were observed. In the control group, there were no significant enhancements in heart function or ACVIM class. Conclusions: This finding suggests that pDSCs could be a supplement for valvular heart disease treatment.

  5. Dose-dependent effects of intravenous alcohol administration on cerebral blood flow in young adults.

    Science.gov (United States)

    Strang, Nicole M; Claus, Eric D; Ramchandani, Vijay A; Graff-Guerrero, Ariel; Boileau, Isabelle; Hendershot, Christian S

    2015-02-01

    Functional magnetic resonance imaging (fMRI) studies involving alcohol challenge are important for identifying neural correlates of alcohol's psychopharmacological effects. However, evaluating acute alcohol effects on blood oxygen level-dependent (BOLD) signal change is complicated by alcohol-related increases in cerebral blood flow (CBF). The present study aimed to further characterize acute alcohol effects on CBF using intravenous alcohol administration to maximize control over brain alcohol exposure. Twenty heavy-drinking young adults (M = 19.95 years old, SD = 0.76) completed alcohol and placebo imaging sessions in a within-subject, counter-balanced, placebo-controlled design. Arterial spin labeling (ASL) provided estimates of perfusion change at two target blood alcohol concentrations (40 and 80 mg%) relative to baseline and relative to a saline control infusion. Voxel-wise analyses showed widespread and dose-dependent effects of alcohol on CBF increase. Region-of-interest analyses confirmed these findings, also indicating regional variation in the magnitude of perfusion change. Additional findings indicated that lower self-reported sensitivity to alcohol corresponded with reduced perfusion change during alcohol administration. This study provides further evidence for widespread effects of acute alcohol on cerebral perfusion, also demonstrating regional, dose-dependent, and inter-individual variation. Further research is needed to evaluate implications of these effects for the design and interpretation of pharmacological fMRI studies involving alcohol challenge.

  6. Disposition of methyl ethyl ketoxime in the rat after oral, intravenous and dermal administration.

    Science.gov (United States)

    Burka, L T; Black, S R; Mathews, J M

    1998-10-01

    1. The disposition of 14C-methyl ethyl ketoxime (MEKO) was determined in the male F344 rat following oral, intravenous (i.v.) and dermal administration. 2. Oral doses of 2.7, 27 and 270 mg/kg were primarily excreted as CO2 (71-49%) in decreasing percentage as the dose increased. Excretion in urine (13-26%) and as volatiles (5-18%) increased as the dose increased. Five to 6% of the dose remained in the major tissues after 72 h. 3. An i.v. dose of 2.7 mg/kg was also principally excreted as CO2 (48.8%) with excretion in urine and as expired volatiles accounting for 21.4 and 11.4%, respectively. About 7% of the administered radioactivity remained in the tissues after 72 h. 4. Following dermal administration, 13 and 26% of a 2.7 and 270 mg/kg dose, respectively, were absorbed. Volatilization from the dose site prior to placement in the metabolism cage may account for the low absorption. 5. MEKO was biotransformed to at least five polar metabolites that could only be partially resolved by anion exchange chromatography. Incubation with glucuronidase, but not sulphatase, changed the urinary metabolic profile. Methyl ethyl ketone was a major component in the volatiles.

  7. Pharmacokinetics of marbofloxacin after intravenous and intramuscular administration in Hanwoo, Korean native cattle.

    Science.gov (United States)

    Belew, Sileshi; Kim, Jin-Yoon; Hossain, Md Akil; Park, Ji-Yong; Lee, Seung-Jin; Park, Yong-Soo; Suh, Joo-Won; Kim, Jong-Choon; Park, Seung-Chun

    2015-03-01

    Pharmacokinetic (PK) parameters of marbofloxacin (MRFX) in Korean cattle, Hanwoo, were determined following its intravenous (i.v.) or intramuscular (i.m.) administration at a dose of 2 mg/kg. Area under the curve (AUC0-24 hr), half-life (t1/2) and total body clearance (CLB) of i.v. MRFX were 6.87 hr∙µg/ml, 2.44 hr and 0.29 l/kg∙hr, respectively, and the corresponding values for i.m. administration of MRFX were 5.07 hr∙µg/ml, 2.44 hr and 0.39 l/kg∙hr. The suggested optimal doses of MRFX in Hanwoo cattle, calculated by integration of PK data obtained in the present study and previously reported minimum inhibitory concentration (MIC) for MRFX against susceptible (MIC ≤1 µg/ml) and intermediate (MIC ≤2 µg/ml) pathogenic bacteria, were 2.1 and 4.2 mg/kg/day by i.v. route and 3.9 and 7.8 mg/kg/day by i.m. route.

  8. Toxicological evaluation of long-term intravenous administration of amitraz in horses

    Directory of Open Access Journals (Sweden)

    Queiroz-Neto A.

    2002-01-01

    Full Text Available With the aim of determining the possible toxicity of amitraz after its prolonged use in horses, six English Thoroughbred horses received intravenous injections of amitraz (0.05, 0.10 or 0.15 mg/kg weekly for four months, constituting the experimental group. Eight other animals (control group, via the same route following the same drug administration schedule and period of time, received the vehicle, dimethylformamide. At the end of this period, blood was collected from all the animals, and a comparison was made of the means of the values obtained for the various blood analyses: complete hemogram, alkaline phosphatase, gamma-glutamyltransferase, blood urea nitrogen, lactate dehydrogenase, aspartate aminotransferase, creatine phosphokinase, glucose, albumin, total protein, creatinine, Na+ , K+, Cl- and CO2. The results for the biochemical characteristics showed that only the mean value for urea of the animals submitted to treatment with amitraz was significantly different than the mean value obtained for the control group. The analyses of the hematological characteristics showed that no significant differences between groups were observed. Similarly, the measurement of blood electrolyte levels demonstrated that long-term treatment with amitraz did not cause significant changes in the variables analyzed. The results indicate that amitraz, given in the doses employed in this study, did not show signs of inducing toxic effects in vital organs, even after prolonged administration.

  9. Methylphenidate enhances the abuse-related behavioral effects of nicotine in rats: intravenous self-administration, drug discrimination, and locomotor cross-sensitization.

    Science.gov (United States)

    Wooters, Thomas E; Neugebauer, Nichole M; Rush, Craig R; Bardo, Michael T

    2008-04-01

    Stimulant drugs, including D-amphetamine, cocaine, and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination, and locomotor cross-sensitization procedures. Adult male Sprague-Dawley rats were trained to respond for intravenous nicotine (0.01 or 0.03 mg/kg/infusion) or sucrose, and the acute effects of methylphenidate (1.25-10 mg/kg) were determined; in addition, separate groups of rats were treated with methylphenidate (2.5 mg/kg) or saline before 12 consecutive nicotine (0.03 mg/kg/infusion) self-administration sessions. Next, the discriminative stimulus effects of nicotine (0.03-0.3 mg/kg) and methylphenidate (1.25-10 mg/kg), alone and in combination with a low nicotine dose (0.056 mg/kg), were tested in nicotine-trained rats. Finally, the locomotor effect of repeated methylphenidate (2.5 mg/kg) was tested in rats previously treated with nicotine (0.2-0.8 mg/kg). Results indicated that acute methylphenidate increased the rate of nicotine self-administration at doses that reduced sucrose-maintained responding; furthermore, tolerance to this effect was not apparent following repeated methylphenidate. Methylphenidate, while not substituting for nicotine alone, dose-dependently enhanced the discriminative stimulus effect of a low nicotine dose. In addition, repeated nicotine exposure promoted the development of locomotor sensitization to methylphenidate. Taken together with recent clinical findings, these results suggest that methylphenidate may enhance the abuse-related behavioral effects of nicotine, perhaps increasing vulnerability to tobacco dependence.

  10. Marbofloxacin disposition after intravenous administration of a single dose in wild mallard ducks (Anas platyrhynchos).

    Science.gov (United States)

    Garcia-Montijano, Marino; de Lucas, J Julio; Rodríguez, Casilda; González, Fernando; San Andrés, Manuel Ignacio; Waxman, Samanta

    2012-03-01

    Marbofloxacin, a fluoroquinolone developed specifically for veterinary use, has demonstrated considerable pharmokinetic variation among avian species. The goal of this study was to determine the disposition kinetics of marbofloxacin in mallard ducks (Anas platyrhynchos) after a single intravenous injection. Six wild mallard ducks were used in the study. Marbofloxacin was injected at a dose of 2 mg/kg into the basilic vein, and blood was subsequently collected at regular intervals from each bird. Plasma marbofloxacin concentrations were determined by using high-performance liquid chromatography. The volume of distribution at steady state was 1.78 +/- 0.37 L/kg, and the total plasma clearance was 0.59 +/- 0.08 L/kg per hour. Marbofloxacin had a relatively short permanence, with a elimination half-life of 2.81 +/- 1.20 hours, a terminal half-life of 2.43 +/- 0.61 hours, and a mean residence time of 2.99 +/- 0.52 hour. The maximum observed concentration (Cmax) and area under the curve (AUC) were 1.34 +/- 0.27 microg/mL and 3.75 +/- 0.56 microg x h/mL, respectively. Values of minimum inhibitory concentration (MIC), Cmax, and AUC have been used to predict the clinical efficacy of a drug in treating bacterial infections, with a Cmax: MIC value of 10 and an AUC: MIC ratio of 125-250 associated with optimal bactericidal effects. By using the study data and MIC breakpoints of 0.125 microg/mL or 0.2 microg/mL, values derived for Cmax: MIC were 9.37 +/- 0.99 and 5.85 +/- 0.62, respectively, and for AUC: MIC were 29.99 +/- 4.51 and 18.74 +/- 2.82, respectively. By using MIC values of 0.125 and 0.2 microg/mL and a target AUC: MIC = 125, the calculated optimal daily marbofloxacin dosages for mallard ducks were 9.24 and 14.78 mg/kg, respectively. These results suggest that, primarily because of the high total plasma clearance observed, the marbofloxacin dose for treatment of bacterial diseases in mallard ducks should be increased after intravenous administration. Intravenous doses

  11. The optimal choice of medication administration route regarding intravenous, intramuscular, and subcutaneous injection

    Science.gov (United States)

    Jin, Jing-fen; Zhu, Ling-ling; Chen, Meng; Xu, Hui-min; Wang, Hua-fen; Feng, Xiu-qin; Zhu, Xiu-ping; Zhou, Quan

    2015-01-01

    Background Intravenous (IV), intramuscular (IM), and subcutaneous (SC) are the three most frequently used injection routes in medication administration. Comparative studies of SC versus IV, IM versus IV, or IM versus SC have been sporadically conducted, and some new findings are completely different from the dosage recommendation as described in prescribing information. However, clinicians may still be ignorant of such new evidence-based findings when choosing treatment methods. Methods A literature search was performed using PubMed, MEDLINE, and Web of Sciences™ Core Collection to analyze the advantages and disadvantages of SC, IV, and IM administration in head-to-head comparative studies. Results “SC better than IV” involves trastuzumab, rituximab, antitumor necrosis factor medications, bortezomib, amifostine, recombinant human granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, recombinant interleukin-2, immunoglobulin, epoetin alfa, heparin, and opioids. “IV better than SC” involves ketamine, vitamin K1, and abatacept. With respect to insulin and ketamine, whether IV has advantages over SC is determined by specific clinical circumstances. “IM better than IV” involves epinephrine, hepatitis B immu-noglobulin, pegaspargase, and some antibiotics. “IV better than IM” involves ketamine, morphine, and antivenom. “IM better than SC” involves epinephrine. “SC better than IM” involves interferon-beta-1a, methotrexate, human chorionic gonadotropin, hepatitis B immunoglobulin, hydrocortisone, and morphine. Safety, efficacy, patient preference, and pharmacoeconomics are four principles governing the choice of injection route. Safety and efficacy must be the preferred principles to be considered (eg, epinephrine should be given intramuscularly during an episode of systemic anaphylaxis). If the safety and efficacy of two injection routes are equivalent, clinicians should consider more about patient preference and

  12. Intravenous administration of lidocaine directly acts on spinal dorsal horn and produces analgesic effect: An in vivo patch-clamp analysis

    OpenAIRE

    Miyuki Kurabe; Hidemasa Furue; Tatsuro Kohno

    2016-01-01

    Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, although the underlying mechanisms remains unclear. Here, we hypothesized that intravenous lidocaine acts on spinal cord neurons and induces analgesia in acute pain. We therefore examined the action of intravenous lidocaine in the spinal cord using the in vivo patch-clamp technique. We first investigated the effects of intravenous lidocaine using behavioural measures i...

  13. Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration

    Directory of Open Access Journals (Sweden)

    Mohamed Aboubakr

    2014-01-01

    Full Text Available The pharmacokinetics aspects of levofloxacin were studied in healthy and experimentally renal damaged Muscovy ducks after single intravenous (IV and oral (PO dose of 10 mg kg−1 bwt. Following IV administration, elimination half-life (t1/2(β and mean residence time (MRT were longer in renal damaged ducks than in healthy ones. Total clearance (Cltot in renal damaged ducks (0.20 L kg−1 h−1 was significantly lower as compared to that in healthy ones (0.41 L kg−1 h−1. Following PO administration, the peak serum concentration (Cmax was higher in renal damaged than in healthy ducks and was achieved at maximum time (tmax of 2.47 and 2.05 h, respectively. The drug was eliminated (t1/2(el at a significant slower rate (3.94 h in renal damaged than in healthy ducks (2.89 h. The pharmacokinetic profile of levofloxacin is altered in renal damaged ducks due to the increased serum levofloxacin concentrations compared with that in clinically healthy ducks. Oral administration of levofloxacin at 10 mg kg−1 bwt may be highly efficacious against susceptible bacteria in ducks. Also, the dose of levofloxacin should be reduced in renal damaged ducks. Pharmacokinetic/pharmacodynamic integration revealed significantly higher values for Cmax/MIC and AUC/MIC ratios in renal damaged ducks than in healthy ones, indicating the excellent pharmacokinetic characteristics of levofloxacin in renal damaged ducks.

  14. Influence of intravenous L-carnitine administration in sheep preceding an oral urea drench.

    Science.gov (United States)

    Chapa, A M; Fernandez, J M; White, T W; Bunting, L D; Gentry, L R; Ward, T L; Blum, S A

    1998-11-01

    Two experiments were conducted to investigate the effect of i.v. administration of L-carnitine on selected metabolites in sheep and to determine the feasibility of using L-carnitine to ameliorate the deleterious effects of hyperammonemia in sheep. In Exp. 1, i.v. L-carnitine solutions were administered at three levels in a replicated Latin square: 0 (CONT), 6.36 (CAR 1), and 12.72 (CAR 2) mmol L-carnitine/kg x (75) BW using Suffolk ewes (n = 6; average BW 75+/-3 kg). Plasma L-carnitine concentration was increased (P<.05) by treatment (51.9 vs 102.3, and 96.4 micromol/L in CONT, CAR 1, and CAR 2, respectively). Plasma glucose concentration was elevated (P<.05) in CAR 2 and CAR 1. Plasma NEFA concentration was highest (P<.05) in CAR 2. Area under the response curve for glucose was greater (P<.02) in CAR 2. In Exp. 2, Suffolk ewes (n = 16; average BW 48+/-2 kg) were used in a randomized complete block design with a 2x2 factorial treatment arrangement to determine the effects of i.v. L-carnitine administration during an oral urea load test (OULT). L-Carnitine (0 and 6.36 mmol/kg x (75) BW) was administered i.v. at 30 min, and an oral urea drench (50% wt/vol; 0 and 300 mg/kg BW) was administered at 60 min. Plasma L-carnitine was increased (P<.0001) by i.v. L-carnitine. Plasma ammonia N was highest (P<.0001) in the UREA treatment compared with the CONT, CARN, and CARN + UREA treatments (148 vs 95, 101, and 108 micromol/L, respectively). Intravenous L-carnitine administration influenced plasma glucose and NEFA concentrations in sheep and, when administered 30 min preceding an OULT, prevented the development of subclinical hyperammonemia in sheep.

  15. Pharmacokinetics of the antiepileptic drug levetiracetam in healthy Japanese and Caucasian volunteers following intravenous administration.

    Science.gov (United States)

    Toublanc, Nathalie; Okagaki, Takuya; Boyce, Malcolm; Chan, Robert; Mugitani, Ayumi; Watanabe, Shikiko; Yamamoto, Katsumi; Yoshida, Katsumi; Andreas, Jens-Otto

    2015-12-01

    The intravenous (iv) formulation of levetiracetam has been available in clinical practice worldwide for several years, but not in Japan. Two open-label studies were conducted: Study A evaluated the bioequivalence of iv and oral tablet formulations in healthy Japanese volunteers; and Study B subsequently compared the pharmacokinetics of iv levetiracetam in healthy Japanese and Caucasian volunteers. Study A had a randomised, two-way crossover design; a single 1,500 mg levetiracetam dose was administered as a 15-min iv infusion and as 3 × 500 mg oral tablets to Japanese volunteers. In Study B, 1,500 mg levetiracetam was administered as single and repeated 15-min iv infusions to Japanese and Caucasian volunteers. Overall, 26/27 volunteers completed Study A and 32/32 (16 Japanese; 16 Caucasian) completed Study B. In Study A, the point estimate and 90 % confidence interval (CI) for the geometric least squares mean (LSM) ratio (iv vs oral) were fully included within the acceptance range for bioequivalence (0.85-1.25) for the area under plasma concentration-time curve from 0 to last quantifiable observation (AUClast 0.97 [0.95, 0.99]), but not for the maximum plasma concentration (C max 1.64 [1.47, 1.83]). In Study B, after a single iv infusion, the point estimates (90 % CI) for the geometric LSM ratio (Japanese vs Caucasian) for body weight-normalised C max and AUClast were 1.21 (1.07, 1.36) and 0.97 (0.90, 1.04), respectively. Corresponding values after repeated iv infusions were C max,ss 1.01 (0.91, 1.12) and AUCτ,ss 0.89 (0.83, 0.96). Levetiracetam was well tolerated in both studies. Study A did not demonstrate the bioequivalence of single doses of levetiracetam 1,500 mg administered as an iv infusion and as oral tablets in healthy Japanese adults. Study B, however, showed that pharmacokinetic profiles were generally similar between Japanese and Caucasian adults after single and repeated iv infusions of levetiracetam 1,500 mg.

  16. Effect of intravenous or oral sodium chlorate administration on the fecal shedding of Escherichia coli in sheep

    Science.gov (United States)

    The effect of gavage or intravenous (i.v.) administration of sodium chlorate salts on the fecal shedding of generic Escherichia coli in wether lambs was studied. To this end, 9 lambs (27 +/- 2.5 kg) were administered 150 mg NaClO3 per kg BW by gavage or i.v. infusion in a cross-over design with sal...

  17. Quality of abdominal computed tomography angiography: hand versus mechanical intravenous contrast administration in children

    Energy Technology Data Exchange (ETDEWEB)

    Ayyala, Rama S.; Lee, Edward Y. [Boston Children' s Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States); Zurakowski, David [Boston Children' s Hospital and Harvard Medical School, Departments of Anesthesiology and Surgery, Boston, MA (United States)

    2015-11-15

    Abdominal CT angiography has been increasingly used for evaluation of various conditions related to abdominal vasculature in the pediatric population. However, no direct comparison has evaluated the quality of abdominal CT angiography in children using hand versus mechanical administration of intravenous (IV) contrast agent. To compare hand versus mechanical administration of IV contrast agent in the quality of abdominal CT angiography in the pediatric population. We retrospectively reviewed the electronic medical record to identify pediatric patients (≤18 years) who had abdominal CT angiography between August 2012 and August 2013. The information obtained includes: (1) type of administration of IV contrast agent (hand [group 1] versus mechanical [group 2]), (2) size (gauge) of IV catheter, (3) amount of contrast agent administered and (4) rate of contrast agent administration (ml/s). Two reviewers independently performed qualitative and quantitative evaluation of abdominal CT angiography image quality. Qualitative evaluation of abdominal CT angiography image quality was performed by visual assessment of the degree of contrast enhancement in the region of interest (ROI) based on a 4-point scale. Quantitative evaluation of each CT angiography examination was performed by measuring the Hounsfield unit (HU) using an ROI within the abdominal aorta at two levels (celiac axis and the inferior mesenteric artery) for each child. Analysis of variance (ANOVA) using the F-test was applied to compare contrast enhancement within the abdominal aorta at two levels (celiac axis and inferior mesenteric artery) between hand administration and mechanical administration of IV contrast methods with adjustment for age. We identified 46 pediatric patients (24 male, 22 female; mean age 7.3 ± 5.5 years; range 5 weeks to 18 years) with abdominal CT angiography performed during the study period. Of these patients, 16 (35%; 1.7 ± 2.2 years; range 5 weeks to 5 years) had hand

  18. Combination Intravenous and Intra-Articular Tranexamic acid compared with Intravenous Only Administration and No Therapy in Total Knee Arthroplasty: A Case Series Study

    Directory of Open Access Journals (Sweden)

    Chris Buntting

    2016-07-01

    This study supports the existing literature and suggests that the use of IV Tranexamic acid alone or in combination with intra-articular dose in TKA may reduce the requirement for transfusion (Level IV evidence. Furthermore, this study suggests that the use of tranexamic acid as a combination of Intravenous and intra-articular administration has no effect on range of motion, or medical complications during hospital stay. Although it was not a statistically significant finding, our study suggested a trend towards a greater reduction in haemoglobin and haematocrit fall in the combination therapy group when compared to IV Tranexamic acid alone

  19. Pharmacodynamics and pharmacokinetics of flumequine in pigs after single intravenous and intramuscular administration.

    Science.gov (United States)

    Villa, R; Cagnardi, P; Acocella, F; Massi, P; Anfossi, P; Asta, F; Carli, S

    2005-07-01

    The pharmacokinetics and intramuscular (IM) bioavailability of flumequine (15 mgkg(-1)) were investigated in healthy pigs and the findings related to published minimal inhibitory concentrations (MICs) for susceptible bacteria of animal origin, and to experimentally determined MICs for susceptible strains of porcine origin. We found MICs for Escherichia coli, Salmonella spp., Pasteurella spp. and Bordetella spp. in the range 0.5 to >64 microg mL(-1) isolated from infected pigs in the Forli area of Italy; only the Pasteurella multocida strains were sensitive (MIC(90)=0.5 microg mL(-1)). After intravenous (IV) injection, flumequine was slowly distributed and eliminated (t(1/2lambda(1))1.40+/-0.16 h and t(1/2lambda(2))6.35+/-1.69 h). The distribution volume at steady state (V(dss)) was 752.59+/-84.03 mL kg(-1) and clearance (Cl(B)) was 237.19+/-17.88 mL kg(-1)h(-1). After IM administration, peak serum concentration (4.99+/-0.92 microg mL(-1)) was reached between the 2nd and the 3rd hour. The results on MIC of isolated bacteria, although only indicative, suggest that the efficacy of flumequine on Gram-negative bacteria may be impaired by the emergence of less sensitive or resistant strains.

  20. Safe intravenous administration in pediatrics: A 5-year Pediatric Intensive Care Unit experience with smart pumps.

    Science.gov (United States)

    Manrique-Rodríguez, S; Sánchez-Galindo, A C; Fernández-Llamazares, C M; Calvo-Calvo, M M; Carrillo-Álvarez, Á; Sanjurjo-Sáez, M

    2016-10-01

    To estimate the impact of smart pump implementation in a pediatric intensive care unit in terms of number and type of administration errors intercepted. Observational, prospective study carried out from January 2010 to March 2015 with syringe and great volumen infusion pumps available in the hospital. A tertiary level hospital pediatric intensive care unit. Infusions delivered with infusion pumps in all pediatric intensive care unit patients. Design of a drug library with safety limits for all intravenous drugs prescribed. Users' compliance with drug library as well as number and type of errors prevented were analyzed. Two hundred and eighty-three errors were intercepted during 62 months of study. A high risk drug was involved in 58% of prevented errors, such as adrenergic agonists and antagonists, sedatives, analgesics, neuromuscular blockers, opioids, potassium and insulin. Users' average compliance with the safety software was 84%. Smart pumps implementation has proven effective in intercepting high risk drugs programming errors. These results might be exportable to other critical care units, involving pediatric or adult patients. Interdisciplinary colaboration is key to succeed in this process. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  1. [Pharmacokinetics of salvianolic acid A after single intravenous administration in Rhesus monkey].

    Science.gov (United States)

    Song, Jun-ke; Zhang, Wen; Zhang, Wei-ku; Feng, Zhang-ying; Xie, Tao; Du, Guan-Hua

    2015-09-01

    Salvianolic acid A (Sal A) is one of the most effective compounds isolated from the root of Salvia miltiorrhiza. Up to now, several studies regarding the pharmacokinetic profiles of Sal A have been reported, however there is no such study reported in monkeys, the species which is more similar to human. The aim of this study is to develop a LC-MS method for the determination of Sal A in monkey plasma and apply it to the pharmacokinetic studies of monkeys. After single intravenous administration of Sal A, the plasma concentration-time curves were observed and the main pharmacokinetic parameters were calculated. The plasma concentration at 2 min (C2 (min)) values were (28.343 ± 6.426), (45.679 ± 12.301) and (113.293 ± 24.360) mg x L(-1) for Rhesus monkeys treated with Sal A at 2.5, 5 and 10 mg x kg(-1). The area under the concentration-time curve (AUC(0-∞)) values were (3.316 ± 0.871), (5.754 ± 2.150) and (13.761 ± 2.825) μg x L(-1) x h, respectively. Furthermore, this method was improved and applied to the simultaneous determination of Sal A, Sal B and Sal C, which provided useful information for preclinical studies and clinical trials of Sal A, Sal B and Sal C.

  2. Ketoprofen-loaded pomegranate seed oil nanoemulsion stabilized by pullulan: Selective antiglioma formulation for intravenous administration.

    Science.gov (United States)

    Ferreira, Luana M; Cervi, Verônica F; Gehrcke, Mailine; da Silveira, Elita F; Azambuja, Juliana H; Braganhol, Elizandra; Sari, Marcel H M; Zborowski, Vanessa A; Nogueira, Cristina W; Cruz, Letícia

    2015-06-01

    This study aimed to prepare pomegranate seed oil nanoemulsions containing ketoprofen using pullulan as a polymeric stabilizer, and to evaluate antitumor activity against in vitro glioma cells. Formulations were prepared by the spontaneous emulsification method and different concentrations of pullulan were tested. Nanoemulsions presented adequate droplet size, polydispersity index, zeta potential, pH, ketoprofen content and encapsulation efficiency. Nanoemulsions were able to delay the photodegradation profile of ketoprofen under UVC radiation, regardless of the concentration of pullulan. In vitro release study indicates that nanoemulsions were able to release approximately 95.0% of ketoprofen in 5h. Free ketoprofen and formulations were considered hemocompatible at 1 μg/mL, in a hemolysis study, for intravenous administration. In addition, a formulation containing the highest concentration of pullulan was tested against C6 cell line and demonstrated significant activity, and did not reduce fibroblasts viability. Thus, pullulan can be considered an interesting excipient to prepare nanostructured systems and nanoemulsion formulations can be considered promising alternatives for the treatment of glioma.

  3. Compliance with a pediatric clinical practice guideline for intravenous fluid and electrolyte administration.

    Science.gov (United States)

    Hurdowar, Amanda; Urmson, Lynn; Bohn, Desmond; Geary, Denis; Laxer, Ronald; Stevens, Polly

    2009-01-01

    The occurrence of acute hyponatremia associated with cerebral edema in hospitalized children has been increasingly recognized, with over 50 cases of neurological morbidity and mortality reported in the past decade. This condition most commonly occurs in previously healthy children where maintenance intravenous (IV) fluids have been prescribed in the form of hypotonic saline (e.g., 0.2 or 0.3 NaCl). In response to similar problems at The Hospital for Sick Children (six identified through hospital morbidity and mortality reviews and safety reports prior to fall 2007), an interdisciplinary clinician group from our institution developed a clinical practice guideline (CPG) to guide fluid and electrolyte administration for pediatric patients. This article reviews the evaluation of one patient safety improvement to change the prescribing practice for IV fluids in an acute care pediatric hospital, including the removal of the ability to prescribe hypotonic IV solutions with a sodium concentration of team engagement and support from the hospital leadership. A key learning was that a project leader with considerable dedicated time is required during the implementation to develop change concepts, organize and liaise with stakeholders and measure changes in practice. This project highlights the importance of active implementation for policy and guideline documents.

  4. Thyroid function in very low birthweight infants after intravenous administration of the iodinated contrast medium iopromide

    Science.gov (United States)

    Dembinski, J; Arpe, V; Kroll, M; Hieronimi, G; Bartmann, P

    2000-01-01

    BACKGROUND—Thyroid function disorders have often been observed in preterm infants after intravenous administration of iodinated contrast medium. The effect on thyroid function depends on the dosage, but the choice of the contrast medium may be equally important, as there are appreciable pharmacological differences between them.
METHOD—Thyroid function was analysed in 20 very low birthweight infants of gestational age less than 30 weeks after injection of iopromide, a monomeric non-ionic iodinated contrast medium. Levels of free thyroxine and thyroid stimulating hormone were compared with those in 26 control infants.
RESULTS—Free thyroxine levels in all study infants ranged from 9.0 to 25.7 pmol/l (days 14-21) and 9.0 to 23.2 pmol/l (days 35-49), and thyroid stimulating hormone levels ranged from 0.13 to 0.26mU/l (days 14-21) and 0.26 to 11.11 mU/l (days 35-49). These levels were not altered after injection of iopromide.
CONCLUSION—The risk of transient hypothyroidism or hyperthyrotropinaemia may be reduced with the use of iopromide compared with other contrast media.

 PMID:10794789

  5. Intravenous self-administration of mephedrone, methylone and MDMA in female rats.

    Science.gov (United States)

    Creehan, Kevin M; Vandewater, Sophia A; Taffe, Michael A

    2015-05-01

    Male rats will intravenously self-administer (IVSA) the substituted cathinone stimulants ("bath salts") mephedrone (4-methylmethcathione) and methylone (3,4-methylenedioxymethcathinone) robustly, whereas the IVSA of 3,4-methylenedioxymethamphetamine (MDMA) is inconsistent in many rat models. There are no data available on the self-administration of these drugs in female rats, thus a study was undertaken to contrast them directly. Groups of female Wistar rats were trained to self-administer mephedrone, methylone or MDMA (0.5 mg/kg/inf) under a Fixed-Ratio (FR) 1 schedule of reinforcement for 14 sessions. Following the acquisition interval, animals were evaluated in FR (0.0, 0.125, 0.25, 0.5, 1.0, 2.5 mg/kg/inf) and PR (0.125, 1.0 mg/kg/inf) dose-substitution procedures. The results show that female rats acquired the self-administration of all three compounds with intakes in mephedrone-trained rats that were significantly higher than that of methylone-trained or MDMA-trained rats. In dose-substitution under either FR or PR contingencies, however, the potencies of all three drugs were similar within the original training groups. The mephedrone-trained animals exhibited higher intakes of all drugs during dose-substitution, indicating lasting consequences of the training drug. Abuse liability of these three compounds is therefore predicted to be similar in established stimulant users but may differ in liability if they are primary drugs of initiation.

  6. Pharmacokinetic behavior of meloxicam in loggerhead sea turtles (Caretta caretta) after intramuscular and intravenous administration.

    Science.gov (United States)

    Lai, Olimpia R; Di Bello, Antonio; Soloperto, Simona; Freggi, Daniela; Marzano, Giacomo; Cavaliere, Leonardo; Crescenzo, Giuseppe

    2015-04-01

    Data on reptile analgesia are scarce for nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids and almost completely lacking in sea turtles, even though emergencies requiring correct pain management are very frequent in their rehabilitative medicine; therefore, dosage regimens extrapolated from other species involve the risk of clinical failure and damage to the animals. We describe the pharmacokinetic behavior of meloxicam in the loggerhead sea turtle (Caretta caretta). We chose meloxicam because of its selective anti-cyclooxygenase-2 activity and lesser adverse side effects. No data are available on the capacity of turtles to tolerate NSAIDs, so we chose a dose of 0.1 mg/kg of meloxicam. Plasma concentrations of meloxicam were unexpectedly low both for intravenous (IV; maximum concentration [C(max)] = 0.04±0.02 µg/mL) and intramuscular (IM; C(max) = 0.07±0.09 µg/mL) administration. A double-peak phenomenon occurred after both IV (time for second peak concentration T(max2) = 10.33±10.89 h) and IM (T(max2) = 1.17±0.75 h). The second peak after IM injection was premature, so some difficulty and delay in absorption appears to be an appropriate explanation. Furthermore, the area under the curve, and therefore systemic bioavailability (F = 31.82±28.24%), after both IV (0.30±0.29) and IM (0.10±0.03) injection appeared particularly limited. Terminal elimination slope and mean residence time indicated fast elimination after IM dosing; as a consequence, plasma concentrations dropped below analytic limits in 8 h. Considering that IM is the favored route of administration of drugs in rescue centers, it is unlikely that meloxicam at 0.1 mg/kg is an appropriate choice, particularly in long-term pain management protocols.

  7. Pharmacokinetics of gamithromycin after intravenous and subcutaneous administration in broiler chickens.

    Science.gov (United States)

    Watteyn, A; Plessers, E; Wyns, H; De Baere, S; De Backer, P; Croubels, S

    2013-06-01

    Gamithromycin is a new macrolide antibiotic that is only registered for use in cattle to treat respiratory disorders such as bovine respiratory disease. The aim of this study was to determine the pharmacokinetics of gamithromycin in broiler chickens. Gamithromycin (6 mg/kg of BW) was injected intravenously (IV) or subcutaneously (SC) to six 4-wk-old chickens in a parallel study design, and blood was collected at different time points postadministration. Quantification of gamithromycin in plasma was performed using an in-house validated liquid chromatography-tandem mass spectrometry method and the pharmacokinetics analyzed according to a 2-compartmental model. Following IV administration, the mean area under the plasma concentration-time curve (AUC0→∞), and α and β half-life of elimination (t1/2el α and t1/2el β) were 3,998 h•ng/mL, 0.90 h, and 14.12 h, respectively. Similar values were obtained after a SC bolus injection, i.e., 4,095 h•ng/mL, 0.34 h, and 11.63 h, for AUC0→∞, t1/2el α, and t1/2el β, respectively. The mean maximum plasma concentration (889.46 ng/mL) appeared at 0.13 h. Gamithromycin showed a large volume of distribution after IV as well as SC administration, 27.08 and 20.89 L/kg, respectively, and a total body clearance of 1.61 and 1.77 L/h•kg, respectively. The absolute bioavailability was 102.4%, showing that there is a complete absorption of gamithromycin after a SC bolus injection of 6 mg/kg of BW.

  8. The optimal choice of medication administration route regarding intravenous, intramuscular, and subcutaneous injection

    Directory of Open Access Journals (Sweden)

    Jin JF

    2015-07-01

    Full Text Available Jing-fen Jin,1 Ling-ling Zhu,2 Meng Chen,3 Hui-min Xu,3 Hua-fen Wang,1 Xiu-qin Feng,1 Xiu-ping Zhu,3 Quan Zhou31Division of Nursing, 2VIP Care Ward, Division of Nursing, 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaBackground: Intravenous (IV, intramuscular (IM, and subcutaneous (SC are the three most frequently used injection routes in medication administration. Comparative studies of SC versus IV, IM versus IV, or IM versus SC have been sporadically conducted, and some new findings are completely different from the dosage recommendation as described in prescribing information. However, clinicians may still be ignorant of such new evidence-based findings when choosing treatment methods.Methods: A literature search was performed using PubMed, MEDLINE, and Web of Sciences™ Core Collection to analyze the advantages and disadvantages of SC, IV, and IM administration in head-to-head comparative studies.Results: “SC better than IV” involves trastuzumab, rituximab, antitumor necrosis factor medications, bortezomib, amifostine, recombinant human granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, recombinant interleukin-2, immunoglobulin, epoetin alfa, heparin, and opioids. “IV better than SC” involves ketamine, vitamin K1, and abatacept. With respect to insulin and ketamine, whether IV has advantages over SC is determined by specific clinical circumstances. “IM better than IV” involves epinephrine, hepatitis B immunoglobulin, pegaspargase, and some antibiotics. “IV better than IM” involves ketamine, morphine, and antivenom. “IM better than SC” involves epinephrine. “SC better than IM” involves interferon-beta-1a, methotrexate, human chorionic gonadotropin, hepatitis B immunoglobulin, hydrocortisone, and morphine. Safety, efficacy, patient preference, and pharmacoeconomics are four principles

  9. Pharmacokinetics of Flunixin Meglumine After Intravenous and Intramuscular Administration in Pigs

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Pharmacokinetics of flunixin meglumine (FM) was investigated in 14 healthy pigs following single intravenous (i.v.) and intramuscular (i.m.) administration of the drug at the dosage of 2.2 and 1.1 mg kg-1. Blood samples were collected at different intervals after administration, and concentrations of FM were determined by HPLC method with a limit of detection of 0.1 μg mL-1. The FM concentration-time data were fitted to a two-compartment open model after single i.v.dosing in pigs. The main pharmacokinetic parameters were as follows: t1/2α, 0.49 ±0.03 and 0.58 ±0.07 h; t1.2β, 6.28±0.13 and 7.37 ±0.59 h; V/F, 0.01 ±0.001 and 0.01±0.002 L kg-1; CL, 0.01 ±0.002 and 0.01±0.002 L h-1; AUC, 237.73 ±52.46 and 147.71±36.76 μg h-1 mL-1. The drug concentration-time data were fitted to a two-compartment model with first-order absorption after single i.m. administration in pigs. The main pharmacokinetic parameters were as follows: t1/2α, 0.90±0.07 and 0.86±0.10 h;t1/2β, 8.79±0.85 and 9.60±0.10 h; V/F, 0.02±0.004 and 0.02±0.003 L kg-1; CL, 0.01±0.002 and 0.01 ±0.003 L h-1; AUC, 174.63± 45.84 and 112.42 ±31.19 μg h-1 mL-1. The results of the present study showed that FM was rapidly absorbed, extensively distributed, and slowly eliminated in pigs. The drug was completely absorbed after single i.m. administration and a good bioavailability in pigs.

  10. Behavioural effects of rapid intravenous administration of meta-chlorophenylpiperazine in patients with panic disorder and controls.

    Science.gov (United States)

    van der Wee, Nic J A; Fiselier, Jasha; van Megen, Harold J G M; Westenberg, Herman G M

    2004-10-01

    Oral and intravenous challenge paradigms with the direct 5-HT agonist meta-chlorophenylpiperazine (m-CPP) in panic disorder (PD) have shown only moderate sensitivity or selectivity of the panicogenic effects in PD. However, the results of a study examining the effects of rapid intravenous administration of 0.1 mg/kg of m-CPP in healthy volunteers suggested that this approach may be a more selective and sensitive panicogenic paradigm in PD. We therefore compared the behavioural, neuroendocrine and physiological effects of rapid intravenous administration of 0.1 mg/kg of m-CPP in 10 patients with PD and 10 healthy controls. Panic attacks were significantly more provoked in patients with PD (90%) compared to healthy controls (0%). Effects on the behavioural, but not on the neuroendocrine and physiological parameters, were significantly greater in patients. Our data suggests that the behavioural effects of rapid intravenous administration of 0.1 mg/kg of m-CPP in patients with PD indeed show a unique combination of high sensitivity and selectivity.

  11. Pharmacokinetic evaluation of pamidronate after oral administration: a study on dose proportionality, absolute bioavailability, and effect of repeated administration

    DEFF Research Database (Denmark)

    Hyldstrup, Lars; Flesch, G; Hauffe, S A

    1993-01-01

    30 minutes at constant infusion rate. Repeated peroral doses (75 and 150 mg) were administered to 12 females (aged 51-70 years) for 10 consecutive days. Urinary excretion of pamidronate after peroral and i.v. administration was used for estimation of pamidronate absorption. Renal excretion...

  12. Pharmacokinetics and antinociceptive effects of tramadol and its metabolite O-desmethyltramadol following intravenous administration in sheep.

    Science.gov (United States)

    Bortolami, E; Della Rocca, G; Di Salvo, A; Giorgi, M; Kim, T W; Isola, M; De Benedictis, G M

    2015-09-01

    Although sheep are widely used as an experimental model for various surgical procedures there is a paucity of data on the pharmacokinetics and efficacy of analgesic drugs in this species. The aims of this study were to investigate the pharmacokinetics of intravenously (IV) administered tramadol and its active metabolite O-desmethyltramadol (M1) and to assess the mechanical antinociceptive effects in sheep. In a prospective, randomized, blinded study, six healthy adult sheep were given 4 and 6 mg/kg tramadol and saline IV in a cross-over design with a 2-week wash-out period. At predetermined time points blood samples were collected and physiological parameters and mechanical nociceptive threshold (MNT) values were recorded. The analytical determination of tramadol and M1 was performed using high performance liquid chromatography. Pharmacokinetic parameters fitted a two- and a non-compartmental model for tramadol and M1, respectively. Normally distributed data were analysed by a repeated mixed linear model. Plasma concentration vs. time profiles of tramadol and M1 were similar after the two doses. Tramadol and M1 plasma levels decreased rapidly in the systemic circulation, with both undetectable after 6 h following drug administration. Physiological parameters did not differ between groups; MNT values were not statistically significant between groups at any time point. It was concluded that although tramadol and M1 concentrations in plasma were above the human minimum analgesic concentration after both treatments, no mechanical antinociceptive effects of tramadol were reported. Further studies are warranted to assess the analgesic efficacy of tramadol in sheep. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin after intravenous and intramuscular administration in beagle dogs.

    Science.gov (United States)

    Yohannes, Sileshi; Awji, Elias Gebru; Lee, Seung-Jin; Park, Seung-Chun

    2015-03-01

    1.The aim of the present study was to determine the PKs of marbofloxacin in beagle dogs after intravenous (i.v.) and intramuscular (i.m.) administration, the ex vivo and in vitro PK/PD indices of marbofloxacin against clinical isolates of Staphylococcus pseudintermedius, and the ex vivo AUC/MIC ratios associated with different levels of antibacterial activity. 2.After i.v. of marbofloxacin (2 mg/kg), the mean ± SEM values of AUC, t1/2β, Vss, and CL were 8.47 ± 3.51 h µg/mL, 8.08 ± 6.25 h, 2.32 ± 1.00 L/kg and 0.23 ± 0.06 L/kg/h and corresponding values after intramuscular injection were 11.37 ± 3.07 h µg/mL, 7.51 ± 3.70, 1.80 ± 0.90 L/kg and 0.17 ± 0.04 L/kg/h. After i.m. administration, a Cmax of 1.76 ± 0.09 µg/mL was achieved at Tmax of 0.47 ± 0.08 h. The ex-vivo AUC/MIC ratios required to produce bacteriostasis, bactericidal action and elimination of S. pseudintermedius were 65.03, 97.02 and 136.84 h. 3.The in vivo AUC/MIC ratios obtained after i.v. and i.m. administration of 2 mg/kg marbofloxacin (67.76 ± 1.23 and 91.18 ± 2.61) were below the ex vivo AUC/MIC ratios required for bactericidal activity and bacterial elimination (97.02 ± 9.24 2 mg/kg and 136.21 ± 7.58), suggesting that the recommended daily dosage (2 mg/kg) may not suffice to kill and eradicate S. pseudintermedius strains encountered in clinical area.

  14. Toxicokinetics of tabun enantiomers in anaesthetized swine after intravenous tabun administration.

    Science.gov (United States)

    Tenberken, O; Mikler, J; Hill, I; Weatherby, K; Thiermann, H; Worek, F; Reiter, G

    2010-10-05

    In the present study, we report the first in vivo toxicokinetic study of tabun (O-ethyl-N,N-dimethylphosphoramidocyanidate). The toxicokinetics of the enantiomers of tabun were investigated in anesthetized swine after intravenous administration of 3xLD(50) (161.4mug/kg) tabun. Blood samples were taken for gas chromatographic-mass spectrometric determination of the tabun enantiomers and for measurement of the activity of red blood cell acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE). The tabun enantiomers could be quantified in swine blood to a minimum concentration of 3.0pg/ml (18.5pM) and could be detected to a minimum concentration of 1.0pg/ml (6.2pM). The concentration-time profiles of both tabun enantiomers were best described by a bi-exponential equation. The elimination of (+)-tabun and (-)-tabun were comparable in the initial phase. In the terminal phase a remarkable difference was found, with terminal half lives of 11.5min for (+)-tabun and 23.1min for (-)-tabun. (+)-Tabun showed a markedly longer persistence in vivo than (+)-enantiomers of other G-type nerve agents and could be detected in all swine at least up to 30min post-injection, (-)-tabun at least up to 90min post-injection. These results demonstrate a rather rapid elimination of tabun enantiomers in vivo and may provide a toxicokinetic basis for the further development and optimization of medical countermeasures against this nerve agent.

  15. Pharmacokinetics of doxycycline in laying hens after intravenous and oral administration.

    Science.gov (United States)

    Yang, F; Si, H B; Wang, Y Q; Zhao, Z S; Zhou, B H; Hao, X Q

    2016-08-01

    The pharmacokinetics of doxycycline in laying hens was investigated after a single intravenous (IV) or an oral (PO) dose at 20 mg/kg body weight. The concentrations of doxycycline in plasma samples were determined by high-performance liquid chromatography with an ultraviolet detector, and pharmacokinetic parameters were calculated using a compartmental model method. The disposition of doxycycline after one single IV injection was best described by a two-compartment open model and the main pharmacokinetic parameters were as follows: volume of distribution (Vd) was 865.15 ± 127.64 ml/kg, distribution rate constant (α) was (2.28 ± 0.38) 1/h, elimination rate constant (β) was 0.08 ± 0.02 1/h and total body clearance (Cl) was104.11 ± 18.32 ml/h/kg, while after PO administration, the concentration versus time curve was best described by a one-compartment open model and absorption rate constant (Ka), peak concentration (Cmax), time to reach Cmax (tmax) and absolute bioavailability (F) were 2.55 ± 1.40 1/h, 5.88 ± 0.70 μg/ml, 1.73 ± 0.75 h and 52.33%, respectively. The profile of doxycycline exhibited favourable pharmacokinetic characteristics in laying hens, such as quick absorption and slow distribution and elimination, though oral bioavailability was relatively low. A multiple-dosing regimen (a dose of 20 mg/kg/d for 3 consecutive days) of doxycycline was recommended to treat infections in laying hens. But a further study should be conducted to determine the withdrawal time of doxycycline in eggs.

  16. Pharmacokinetics of fluconazole following intravenous and oral administration to koalas (Phascolarctos cinereus).

    Science.gov (United States)

    Black, L A; Krockenberger, M B; Kimble, B; Govendir, M

    2014-02-01

    Clinically normal koalas (n = 12) received a single dose of 10 mg/kg fluconazole orally (p.o.; n = 6) or intravenously (i.v.; n = 6). Serial plasma samples were collected over 24 h, and fluconazole concentrations were determined using a validated HPLC assay. A noncompartmental pharmacokinetic analysis was performed. Following i.v. administration, median (range) plasma clearance (CL) and steady-state volume of distribution (Vss ) were 0.31 (0.11-0.55) L/h/kg and 0.92 (0.38-1.40) L/kg, respectively. The elimination half-life (t1/2 ) was much shorter than in many species (i.v.: median 2.25, range 0.98-6.51 h; p.o.: 4.69, range 2.47-8.01 h), and oral bioavailability was low and variable (median 0.53, range 0.20-0.97). Absorption rate-limited disposition was evident. Plasma protein binding was 39.5 ± 3.5%. Although fluconazole volume of distribution (Varea ) displayed an allometric relationship with other mammals, CL and t1/2 did not. Allometrically scaled values were approximately sevenfold lower (CL) and sixfold higher (t1/2 ) than observed values, highlighting flaws associated with this technique in physiologically distinct species. On the basis of fAUC/MIC pharmacodynamic targets, fluconazole is predicted to be ineffective against Cryptococcus gattii in the koala as a sole therapeutic agent administered at 10 mg/kg p.o. every 12 h. © 2013 John Wiley & Sons Ltd.

  17. An unusual case of homicide by use of repeated administration of organophosphate insecticides.

    Science.gov (United States)

    De Letter, E A; Cordonnier, J A C M; Piette, M H A

    2002-03-01

    We present an unusual murder case by use of repeated administration of organophosphate insecticides. A 49-year-old woman suffering from mental retardation, epileptic fits and acromegaly was poisoned by her husband. At first, her death was considered as a 'sudden and unexpected' natural death. Abdominal abscesses of pancreatic origin found at autopsy were compatible with repeated administration of pesticides with anticholinergic action. In her medical history at least one episode consistent with an organophosphate intoxication was retrieved. Thorough inquiry revealed that the victim had ingested phosphamidon and/or omethoate orally. Organophosphate intoxication should be considered when unexplained neurological symptoms are associated with pancreatic disturbances.

  18. Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration

    OpenAIRE

    Shin Chang-Sik; Jung Donald; Borghini-Fuhrer Isabelle; Duparc Stephan; Morris Carrie A; Fleckenstein Lawrence

    2011-01-01

    Abstract Artesunate (AS) is a clinically versatile artemisinin derivative utilized for the treatment of mild to severe malaria infection. Given the therapeutic significance of AS and the necessity of appropriate AS dosing, substantial research has been performed investigating the pharmacokinetics of AS and its active metabolite dihydroartemisinin (DHA). In this article, a comprehensive review is presented of AS clinical pharmacokinetics following administration of AS by the intravenous (IV), ...

  19. Long-term intravenous administration of carboxylated single-walled carbon nanotubes induces persistent accumulation in the lungs and pulmonary fibrosis via the nuclear factor-kappa B pathway

    Science.gov (United States)

    Qin, Yue; Li, Suning; Zhao, Gan; Fu, Xuanhao; Xie, Xueping; Huang, Yiyi; Cheng, Xiaojing; Wei, Jinbin; Liu, Huagang; Lai, Zefeng

    2017-01-01

    Numerous studies have demonstrated promising application of single-walled carbon nanotubes (SWNTs) in drug delivery, diagnosis, and targeted therapy. However, the adverse health effects resulting from intravenous injection of SWNTs are not completely understood. Studies have shown that levels of “pristine” or carboxylated carbon nanotubes are very high in mouse lungs after intravenous injection. We hypothesized that long-term and repeated intravenous administration of carboxylated SWNTs (c-SWNTs) can result in persistent accumulation and induce histopathologic changes in rat lungs. Here, c-SWNTs were administered repeatedly to rats via tail-vein injection for 90 days. Long-term intravenous injection of c-SWNTs caused sustained embolization in lung capillaries and granuloma formation. It also induced a persistent inflammatory response that was regulated by the nuclear factor-kappa B signaling pathway, and which resulted in pulmonary fibrogenesis. c-SWNTs trapped within lung capillaries traversed capillary walls and injured alveolar epithelial cells, thereby stimulating production of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and pro-fibrotic growth factors (transforming growth factor-beta 1). Protein levels of type-I and type-III collagens, matrix metalloproteinase-2, and the tissue inhibitor of metalloproteinase-2 were upregulated after intravenous exposure to c-SWNTs as determined by immunohistochemical assays and Western blotting, which suggested collagen deposition and remodeling of the extracellular matrix. These data suggest that chronic and cumulative toxicity of nanomaterials to organs with abundant capillaries should be assessed if such nanomaterials are applied via intravenous administration. PMID:28115845

  20. Administrative risk quantification of subcutaneous and intravenous therapies in Italian centers utilizing the Failure Mode and Effects Analysis approach

    Directory of Open Access Journals (Sweden)

    Ponzetti C

    2016-08-01

    Full Text Available Clemente Ponzetti,1 Monica Canciani,2 Massimo Farina,2 Sara Era,3 Stefan Walzer4,5 1Gruppo Policlinico di Monza, Alessandria, ANMDO National Association of Hospital Physicians, Bologna, 2Studio EmmEffe Srl, Milan, 3Roche Spa, Monza, Italy; 4MArS Market Access & Pricing Strategy GmbH, Weil am Rhein, 5State University Baden-Wuerttemberg, Health Care Management, Loerrach, Germany Background: In oncology, an important parameter of safety is the potential treatment error in hospitals. The analyzed hypothesis is that of subcutaneous therapies would provide a superior safety benefit over intravenous therapies through fixed-dose administrations, when analyzed with trastuzumab and rituximab.Methods: For the calculation of risk levels, the Failure Mode and Effect Analysis approach was applied. Within this approach, the critical treatment path is followed and risk classification for each individual step is estimated. For oncology and hematology administration, 35 different risk steps were assessed. The study was executed in 17 hematology and 16 breast cancer centers in Italy. As intravenous and subcutaneous were the only injection routes in medical available for trastuzumab and rituximab in oncology at the time of the study, these two therapies were chosen.Results: When the risk classes were calculated, eight high-risk areas were identified for the administration of an intravenous therapy in hematology or oncology; 13 areas would be defined as having a median-risk classification and 14 areas as having a low-risk classification (total risk areas: n=35. When the new subcutaneous formulation would be applied, 23 different risk levels could be completely eliminated (65% reduction. Important high-risk classes such as dose calculation, preparation and package labeling, preparation of the access to the vein, pump infusion preparation, and infusion monitoring were included in the eliminations. The overall risk level for the intravenous administration was estimated

  1. Dynamic bioluminescence imaging for quantitative tumour burden assessment using IV or IP administration of d-luciferin: effect on intensity, time kinetics and repeatability of photon emission

    Energy Technology Data Exchange (ETDEWEB)

    Keyaerts, Marleen; Vanhove, Chris; Caveliers, Vicky; Bossuyt, Axel; Lahoutte, Tony [Vrije Universiteit Brussel (VUB), In Vivo Cellular and Molecular Imaging (ICMI) Laboratory, Brussels (Belgium); University Hospital Brussels (UZ-Brussel), Department of Nuclear Medicine, Brussels (Belgium); Verschueren, Jacob [University of Antwerp, Bio-Imaging lab, Department of Biomedical Sciences, Antwerp (Belgium); Bos, Tomas J. [Vrije Universiteit Brussel (VUB), Department of Haematology and Immunology, Brussels (Belgium); Tchouate-Gainkam, Lea O.; Peleman, Cindy [Vrije Universiteit Brussel (VUB), In Vivo Cellular and Molecular Imaging (ICMI) Laboratory, Brussels (Belgium); Breckpot, Karine [Vrije Universiteit Brussel (VUB), Laboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology, Brussels (Belgium)

    2008-05-15

    In vivo bioluminescence imaging (BLI) is a promising technique for non-invasive tumour imaging. d-luciferin can be administrated intraperitonealy or intravenously. This will influence its availability and, therefore, the bioluminescent signal. The aim of this study is to compare the repeatability of BLI measurement after IV versus IP administration of d-luciferin and assess the correlation between photon emission and histological cell count both in vitro and in vivo. Fluc-positive R1M cells were subcutaneously inoculated in nu/nu mice. Dynamic BLI was performed after IV or IP administration of d-luciferin. Maximal photon emission (PE{sub max}) was calculated. For repeatability assessment, every acquisition was repeated after 4 h and analysed using Bland-Altman method. A second group of animals was serially imaged, alternating IV and IP administration up to 21 days. When mice were killed, PE{sub max} after IV administration was correlated with histological cell number. The coefficients of repeatability were 80.2% (IV) versus 95.0% (IP). Time-to-peak is shorter, and its variance lower for IV (p < 0.0001). PE{sub max} was 5.6 times higher for IV. A trend was observed towards lower photon emission per cell in larger tumours. IV administration offers better repeatability and better sensitivity when compared to IP. In larger tumours, multiple factors may contribute to underestimation of tumour burden. It might, therefore, be beneficial to test novel therapeutics on small tumours to enable an accurate evaluation of tumour burden. (orig.)

  2. Permanent relief from intermittent cold stress-induced fibromyalgia-like abnormal pain by repeated intrathecal administration of antidepressants

    Directory of Open Access Journals (Sweden)

    Mukae Takehiro

    2011-09-01

    Full Text Available Abstract Background Fibromyalgia (FM is characterized by chronic widespread pain, which is often refractory to conventional painkillers. Numerous clinical studies have demonstrated that antidepressants are effective in treating FM pain. We previously established a mouse model of FM-like pain, induced by intermittent cold stress (ICS. Results In this study, we find that ICS exposure causes a transient increase in plasma corticosterone concentration, but not in anxiety or depression-like behaviors. A single intrathecal injection of an antidepressant, such as milnacipran, amitriptyline, mianserin or paroxetine, had an acute analgesic effect on ICS-induced thermal hyperalgesia at post-stress day 1 in a dose-dependent manner. In addition, repeated daily antidepressant treatments during post-stress days 1-5 gradually reversed the reduction in thermal pain threshold, and this recovery was maintained for at least 7 days after the final treatment. In addition, relief from mechanical allodynia, induced by ICS exposure, was also observed at day 9 after the cessation of antidepressant treatment. In contrast, the intravenous administration of these antidepressants at conventional doses failed to provide relief. Conclusions These results suggest that the repetitive intrathecal administration of antidepressants permanently cures ICS-induced FM pain in mice.

  3. C-Psilocin tissue distribution in pregnant rats after intravenous administration

    Directory of Open Access Journals (Sweden)

    Francis C.P. Law

    2014-06-01

    Full Text Available Background: Many species of hallucinogenic mushrooms have been found in the genus Psilocybe. The main psychoactive chemicals of Psilocybe mushrooms are psilocin and its phosphoryloxy derivative, psilocybin. In addition to its psychedelic effects, psilocybin is an effective agent to lift the mood of depressed patients with terminal cancers. Objective: To study the dispositional kinetics of 14C-psilocin in pregnant rats after intravenous injection, to calculate tissue dose surrogates i.e., tissue 14C concentration and area under the concentration-time curve using the experimental data, to quantify trans-placental passage of psilocin and/or its metabolites, and to identify new psilocin metabolite(s in rat urine. Methods: A group of 15 pregnant Wistar rats weighing between 0.30-0.36 kg was used in the study. Each rat was given a single dose of 7.5 mg/kg 14C-psilocin i.v. Three rats were randomly selected and sacrificed at 0.5, 1.0, 2.0, 4.0, and 8.0 hr post-dosing. The maternal and fetal tissues were quickly removed and the radioactivity in these tissues determined by liquid scintillation counting. In a separate study, urine samples were collected from 6 male Wistar rats after administering 15 mg/kg of unlabeled psilocin i.p. The urine samples were collected and extracted by chloroform-methanol (9:1 v/v and analyzed using a gas chromatograph/mass spectrometer. Results: 14C-Psilocin crossed the placental barrier of pregnant rats readily after i.v. administration; maternal tissue 14C concentrations were found to be much higher than those in fetal tissues. The areas under the curve for maternal tissues also were much higher than the fetal tissues. In general, maternal tissues could be divided into the fast eliminating organ group, which included the brain (elimination half-life 13 hr. A new psilocin metabolite tentatively identified as dihydroxyindoleacetic acid was found in the urine. Conclusion: Our study showed that psilocin readily crossed the

  4. Video Teleconference Administration of the Repeatable Battery for the Assessment of Neuropsychological Status

    Science.gov (United States)

    Galusha-Glasscock, Jeanine M.; Horton, Daniel K.; Weiner, Myron F.; Cullum, C. Munro

    2016-01-01

    Teleneuropsychology applications are growing, but a limited number of assessment tools have been studied in this context. The present investigation was designed to determine the feasibility and reliability of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) administration by comparing video teleconference (VTC) with face-to-face (FF) test conditions. Eighteen adult subjects over age 55 with and without cognitive impairment were administered Forms A and B of the RBANS in VTC and FF settings in counterbalanced fashion. Similar RBANS scores were obtained in both test conditions, with generally high correlations between administration methods. Results support the feasibility and reliability of remote administration of the RBANS via VTC. PMID:26446834

  5. Repeated administration of histamine improves memory retrieval of inhibitory avoidance by lithium in mice.

    Science.gov (United States)

    Zarrindast, Mohammad Reza; Parsaei, Leila; Ahmadi, Shamseddin

    2008-01-01

    The influence of repeated administration of histamine on lithium-induced state dependency has been investigated. A single-trial step-down inhibitory avoidance task was used to assess memory in adult male NMRI mice. Intraperitoneal (i.p.) administration of lithium (10 mg/kg), immediately after training (post-training), impaired inhibitory avoidance memory on the test day. Pre-test administration of lithium reversed amnesia induced by the drug given after training, with the maximum response at a dose of 10 mg/kg. Repeated intracerebroventricular (i.c.v.) administration of histamine (20 microg/mouse) for 3 consecutive days followed by 5 days of no drug treatment improved memory retrieval of inhibitory avoidance by a pre-test lower dose (5 mg/kg i.p.) of lithium. In contrast, 3 days of i.c.v. injections of both the histamine H1 receptor antagonist pyrilamine (40 microg/mouse) and the histamine H2 receptor antagonist ranitidine (6.25 and 12.5 microg/mouse) prevented the improving effect of pre-test lithium (10 mg/kg i.p.) on memory retrieval. The results suggest that the repeated administration of histaminergic agents may induce a sensitization which affects the memory impairment induced by lithium.

  6. Metabolism and disposition of 1-bromopropane in rats and mice following inhalation or intravenous administration.

    Science.gov (United States)

    Garner, C E; Sumner, S C J; Davis, J G; Burgess, J P; Yueh, Y; Demeter, J; Zhan, Q; Valentine, J; Jeffcoat, A R; Burka, L T; Mathews, J M

    2006-08-15

    Workplace exposure to 1-bromopropane (1-BrP) can potentially occur during its use in spray adhesives, fats, waxes, and resins. 1-BrP may be used to replace ozone depleting solvents, resulting in an increase in its annual production in the US, which currently exceeds 1 million pounds. The potential for human exposure to 1-BrP and the reports of adverse effects associated with potential occupational exposure to high levels of 1-BrP have increased the need for the development of biomarkers of exposure and an improved understanding of 1-BrP metabolism and disposition. In this study, the factors influencing the disposition and biotransformation of 1-BrP were examined in male F344 rats and B6C3F1 mice following inhalation exposure (800 ppm) or intravenous administration (5, 20, and 100 mg/kg). [1,2,3-(13)C]1-BrP and [1-(14)C]1-BrP were administered to enable characterization of urinary metabolites using NMR spectroscopy, LC-MS/MS, and HPLC coupled radiochromatography. Exhaled breath volatile organic chemicals (VOC), exhaled CO(2), urine, feces, and tissues were collected for up to 48 h post-administration for determination of radioactivity distribution. Rats and mice exhaled a majority of the administered dose as either VOC (40-72%) or (14)CO(2) (10-30%). For rats, but not mice, the percentage of the dose exhaled as VOC increased between the mid ( approximately 50%) and high ( approximately 71%) dose groups; while the percentage of the dose exhaled as (14)CO(2) decreased (19 to 10%). The molar ratio of exhaled (14)CO(2) to total released bromide, which decreased as dose increased, demonstrated that the proportion of 1-BrP metabolized via oxidation relative to pathways dependent on glutathione conjugation is inversely proportional to dose in the rat. [(14)C]1-BrP equivalents were recovered in urine (13-17%, rats; 14-23% mice), feces (1-bromopropane to 1-bromo-2-propanol and bromoacetone and following subsequent glutathione conjugation with either of these compounds. Rats

  7. Comparative pharmacokinetics of tetramethylpyrazine phosphate in rat plasma and extracellular fluid of brain after intranasal, intragastric and intravenous administration

    Directory of Open Access Journals (Sweden)

    Dongmei Meng

    2014-02-01

    Full Text Available The purpose of this study was to compare the pharmacokinetic profiles of tetramethylpyrazine phosphate (TMPP in plasma and extracellular fluid of the cerebral cortex of rats via three delivery routes: intranasal (i.n., intragastric (i.g. and intravenous (i.v. administration. After i.n., i.g. and i.v. administration of a single-dose at 10 mg/kg, cerebral cortex dialysates and plasma samples drawn from the carotid artery were collected at timed intervals. The concentration of TMPP in the samples was analyzed by HPLC. The area under the concentration–time curve (AUC and the ratio of the AUCbrain to the AUCplasma (drug targeting efficiency, DTE was calculated to evaluate the brain targeting efficiency of the drug via these different routes of administration. After i.n. administration, TMPP was rapidly absorbed to reach its peak plasma concentration within 5 min and showed a delayed uptake into cerebral cortex (tmax=15 min. The ratio of the AUCbrain dialysates value between i.n. route and i.v. injection was 0.68, which was greater than that obtained after i.g. administration (0.43. The systemic bioavailability obtained with i.n. administration was greater than that obtained by the i.g. route (86.33% vs. 50.39%, whereas the DTE of the nasal route was 78.89%, close to that of oral administration (85.69%. These results indicate that TMPP is rapidly absorbed from the nasal mucosa into the systemic circulation, and then crosses the blood–brain barrier (BBB to reach the cerebral cortex. Intranasal administration of TMPP could be a promising alternative to intravenous and oral approaches.

  8. Administration of gentamicin and ampicillin by continuous intravenous infusion to newborn infants during parenteral nutrition

    DEFF Research Database (Denmark)

    Colding, H; Andersen, G E

    1982-01-01

    Gentamicin and ampicillin were dissolved in an L-amino acid solution especially prepared for newborn infants and infused intravenously over 24 h in 7 babies with serious neonatal surgical problems. Serum concentrations of the antibiotics were maintained rather constant and well above the minimal ...

  9. Intravenøs administration af lipid ved forgiftning med lipofilt laegemiddel

    DEFF Research Database (Denmark)

    Skjønnemand, Martin; Damgaard-Jensen, Jens; Gottschau, Bo

    2011-01-01

    OBJECTIVE: To draw attention to the use of intravenous lipids in the treatment of cardiac arrests caused by overdosage of lipophilic drugs. Case reports and animal studies have shown beneficial use of lipids in severe intoxication. The literature is reviewed. CONCLUSION: Lipids have a place in th...

  10. Repeated administrations of carbon nanotubes in male mice cause reversible testis damage without affecting fertility

    Science.gov (United States)

    Bai, Yuhong; Zhang, Yi; Zhang, Jingping; Mu, Qingxin; Zhang, Weidong; Butch, Elizabeth R.; Snyder, Scott E.; Yan, Bing

    2010-09-01

    Soluble carbon nanotubes show promise as materials for in vivo delivery and imaging applications. Several reports have described the in vivo toxicity of carbon nanotubes, but their effects on male reproduction have not been examined. Here, we show that repeated intravenous injections of water-soluble multiwalled carbon nanotubes into male mice can cause reversible testis damage without affecting fertility. Nanotubes accumulated in the testes, generated oxidative stress and decreased the thickness of the seminiferous epithelium in the testis at day 15, but the damage was repaired at 60 and 90 days. The quantity, quality and integrity of the sperm and the levels of three major sex hormones were not significantly affected throughout the 90-day period. The fertility of treated male mice was unaffected; the pregnancy rate and delivery success of female mice that mated with the treated male mice did not differ from those that mated with untreated male mice.

  11. Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats.

    Science.gov (United States)

    Moreno-Rocha, Luis Alfonso; López-Muñoz, Francisco Javier; Medina-López, José Raúl; Domínguez-Ramírez, Adriana Miriam

    2016-11-01

    Combined administration of certain doses of opioid compounds with a non-steroidal anti-inflammatory drug can produce additive or supra-additive effects while reducing unwanted effects. We have recently reported that co-administration of metamizol with tramadol produces antinociceptive effect potentiation, after acute treatment. However, none information about the effect produced by the combination after chronic or repeated dose administration exists. The aims of this study were to investigate whether the antinociceptive synergism produced by the combination of metamizol and tramadol (177.8 + 17.8 mg/kg, s.c. respectively) is maintained after repeated treatment and whether the effects observed are primarily due to pharmacodynamic interactions or may be related to pharmacokinetics changes. Administration of metamizol plus tramadol acute treatment significantly enhanced the antinociceptive effect of the drugs given alone (P metamizol and tramadol was found under acute treatment (P > 0.05). The mechanism involved in the synergism of the antinociceptive effect observed with the combination of metamizol and tramadol in single dose cannot be attributed to a pharmacokinetic interaction, and other pharmacodynamic interactions have to be considered. On the other hand, when metamizol and tramadol were co-administered under repeated administrations, a pharmacokinetic interaction and tolerance development occurred. Differences found in metamizol active metabolites' pharmacokinetics (P < 0.05) were related to the development of tolerance produced by the combination after repeated doses. This work shows an additional preclinical support for the combination therapy. The clinical utility of this combination in a suitable dose range should be evaluated in future studies.

  12. Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats

    Directory of Open Access Journals (Sweden)

    Luis Alfonso Moreno-Rocha

    2016-11-01

    Full Text Available Combined administration of certain doses of opioid compounds with a non-steroidal anti-inflammatory drug can produce additive or supra-additive effects while reducing unwanted effects. We have recently reported that co-administration of metamizol with tramadol produces antinociceptive effect potentiation, after acute treatment. However, none information about the effect produced by the combination after chronic or repeated dose administration exists. The aims of this study were to investigate whether the antinociceptive synergism produced by the combination of metamizol and tramadol (177.8 + 17.8 mg/kg, s.c. respectively is maintained after repeated treatment and whether the effects observed are primarily due to pharmacodynamic interactions or may be related to pharmacokinetics changes. Administration of metamizol plus tramadol acute treatment significantly enhanced the antinociceptive effect of the drugs given alone (P  0.05. The mechanism involved in the synergism of the antinociceptive effect observed with the combination of metamizol and tramadol in single dose cannot be attributed to a pharmacokinetic interaction, and other pharmacodynamic interactions have to be considered. On the other hand, when metamizol and tramadol were co-administered under repeated administrations, a pharmacokinetic interaction and tolerance development occurred. Differences found in metamizol active metabolites’ pharmacokinetics (P < 0.05 were related to the development of tolerance produced by the combination after repeated doses. This work shows an additional preclinical support for the combination therapy. The clinical utility of this combination in a suitable dose range should be evaluated in future studies.

  13. Intravenous administration of lidocaine directly acts on spinal dorsal horn and produces analgesic effect: An in vivo patch-clamp analysis.

    Science.gov (United States)

    Kurabe, Miyuki; Furue, Hidemasa; Kohno, Tatsuro

    2016-05-18

    Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, although the underlying mechanisms remains unclear. Here, we hypothesized that intravenous lidocaine acts on spinal cord neurons and induces analgesia in acute pain. We therefore examined the action of intravenous lidocaine in the spinal cord using the in vivo patch-clamp technique. We first investigated the effects of intravenous lidocaine using behavioural measures in rats. We then performed in vivo patch-clamp recording from spinal substantia gelatinosa (SG) neurons. Intravenous lidocaine had a dose-dependent analgesic effect on the withdrawal response to noxious mechanical stimuli. In the electrophysiological experiments, intravenous lidocaine inhibited the excitatory postsynaptic currents (EPSCs) evoked by noxious pinch stimuli. Intravenous lidocaine also decreased the frequency, but did not change the amplitude, of both spontaneous and miniature EPSCs. However, it did not affect inhibitory postsynaptic currents. Furthermore, intravenous lidocaine induced outward currents in SG neurons. Intravenous lidocaine inhibits glutamate release from presynaptic terminals in spinal SG neurons. Concomitantly, it hyperpolarizes postsynaptic neurons by shifting the membrane potential. This decrease in the excitability of spinal dorsal horn neurons may be a possible mechanism for the analgesic action of intravenous lidocaine in acute pain.

  14. Intravenous Fluid Bolus Prior to Neonatal and Infant Lumbar Puncture: A Sonographic Assessment of the Subarachnoid Space After Intravenous Fluid Administration.

    Science.gov (United States)

    Rankin, Jessica; Wang, Vincent J; Goodarzian, Fariba; Lai, Hollie A

    2016-03-01

    Neonatal and infant lumbar puncture is a commonly performed procedure in emergency departments, yet traumatic and unsuccessful lumbar punctures occur 30% to 50% of the time. Dehydration may be a risk factor for unsuccessful lumbar punctures, but to our knowledge, no studies have investigated the use of intravenous (IV) fluid bolus prior to lumbar puncture. To investigate the association of IV fluid bolus administration with the sonographic measure of the neonatal and infant lumbar subarachnoid space. We hypothesized that IV fluids would increase subarachnoid space size. Prospective observational study conducted from August 2012 to April 2015.The study took place at the emergency department of the Children's Hospital Los Angeles, an urban pediatric emergency department with an annual census of 76,000 visits.A convenience sample of patients aged 0 to 3 months were enrolled if they had a clinical presentation consistent with pyloric stenosis. This population was used as a proxy because they are similar in age to patients undergoing lumbar puncture for evaluation of neonatal fever and are routinely given IV fluids for dehydration. Patients with a sonographic diagnosis of pyloric stenosis underwent additional ultrasonography evaluation to determine the size of the subarachnoid space before and after IV fluids. Primary outcomes included the difference in the size of the subarachnoid space in millimeters squared before and 1 hour after administration of an IV fluid bolus in the emergency department. Interobserver consistency for the subarachnoid space measurement between attending radiologists was measured using intraclass correlation coefficient. The Wilcoxon signed-rank test was used to examine changes in subarachnoid space measurements (millimeters squared). The study sample consisted of 40 patients with a mean (SD) age of 37 (11.3) days (range, 15-71 days). The mean (SD) size of the subarachnoid space before and 1 hour after IV fluid bolus was 37.8 (11.1) mm(2) and 36

  15. Pharmacokinetics of a novel retinoid AGN 190168 and its metabolite AGN 190299 after intravenous administration of AGN 190168 to rats.

    Science.gov (United States)

    Hsyu, P H; Bowen, B; Tang-Liu, D

    1994-07-01

    The pharmacokinetics of AGN 190168, a novel synthetic retinoid, and its major metabolite, AGN 190299, in rat blood after intravenous administration was investigated. Approximately 4.4 mg kg-1 (high dose) or 0.49 mg kg-1 (low dose) of AGN 190168 was administered to rats via the femoral vein. Blood was collected from the femoral artery at various time points during an 8 h period. Blood concentrations of AGN 190168 and AGN 190299 were determined by a specific and sensitive high-pressure liquid chromatographic (HPLC) method. AGN 190168 was rapidly metabolized in rats. The only detectable drug-related species in the blood was AGN 190299. Therefore, only pharmacokinetics of AGN 190299 were calculated. Elimination of AGN 190299 appeared to be non-linear after administration of the high dose, and linear after administration of the low dose. The maximum elimination rate (Vmax) and the concentration at half of the Vmax (km), as estimated by a Michaelis-Menten one-compartment model, were 7.58 +/- 2.42 micrograms min-1 (mean +/- SD) and 6.10 +/- 1.58 micrograms mL-1, respectively. The value of the area under the blood concentration time curve (AUC) was 9.54 +/- 1.68 micrograms h mL-1 after administration of the high dose and 0.594 +/- 0.095 micrograms h mL-1 after administration of the low dose. The clearance value was 7.79 +/- 1.20 mL min-1 kg-1 after the high dose, statistically significantly different from that after the low dose (p AGN 190168 to AGN 190299, non-linear pharmacokinetics of AGN 190299 after the 4.4 mg kg-1 dose, and the lack of difference in disposition profiles between sexes after intravenous administration of AGN 190168 to rats.

  16. Costs Associated with Intravenous Cancer Therapy Administration in Patients with Metastatic Soft Tissue Sarcoma in a US Population

    Directory of Open Access Journals (Sweden)

    Mei Sheng Duh

    2013-01-01

    Full Text Available Background. The most common chemotherapies in metastatic soft tissue sarcoma (mSTS require intravenous (IV administration. This often requires patients to make multiple outpatient visits per chemotherapy cycle, possibly impeding patients’ daily activities and increasing caregiver burden and medical costs. This study investigated costs associated with IV cancer therapy administration in mSTS from the payer perspective of the health care system. Patients and Methods. From the Experian Healthcare database, 1,228 mSTS patients were selected. Data were analyzed on outpatient visits during 2005–2012 involving IV cancer therapy administration. Costs were estimated on a per patient per visit (PPPV and per patient per month (PPPM basis. Results. The mean (median cost of IV therapy was $2,427 ($1,532 PPPV and $5,468 ($4,310 PPPM, of which approximately 60% was IV drug costs. IV administration costs averaged $399 PPPV and $900 PPPM, representing 16.5% of total visit costs. Anthracycline and alkylating-agents-based therapies had the highest PPPV and PPPM IV administration costs, respectively (mean $479 and $1,336, resp.. Patients with managed care insurance had the highest IV administration costs (mean $504 PPPV; $1,120 PPPM. Conclusions. IV administration costs constitute a considerable proportion of the total costs of receiving an IV cancer therapy to treat mSTS.

  17. Intravenous administration of the conditionally replicative adenovirus Ad5-Δ24RGD induces regression of osteosarcoma lung metastases

    Directory of Open Access Journals (Sweden)

    Gerritsen Winald R

    2008-01-01

    Full Text Available Abstract Metastatic osteosarcoma (OS has a very poor prognosis. New treatments are therefore wanted. The conditionally replicative adenovirus Ad5-Δ24RGD has shown promising anti-tumor effects on local cancers, including OS. The purpose of this study was to determine whether intravenous administration of Ad5-Δ24RGD could suppress growth of human OS lung metastases. Mice bearing SaOs-lm7 OS lung metastases were treated with Ad5-Δ24RGD at weeks 1, 2 and 3 or weeks 5, 6 and 7 after tumor cell injection. Virus treatment at weeks 1–3 did not cause a statistically significant effect on lung weight and total body weight. However, the number of macroscopic lung tumor nodules was reduced from a median of >158 in PBS-treated control mice to 58 in Ad5-Δ24RGD-treated mice (p = 0.15. Moreover, mice treated at weeks 5–7 showed a significantly reduced lung weight (decrease of tumor mass, p 149, p = 0.12 compared to PBS treated control animals. Adenovirus hexon expression was detected in lung tumor nodules at sacrifice three weeks after the last intravenous adenovirus administration, suggesting ongoing viral infection. These findings suggest that systemic administration of Ad5-Δ24RGD might be a promising new treatment strategy for metastatic osteosarcoma.

  18. The pharmacokinetics of methocarbamol and guaifenesin after single intravenous and multiple-dose oral administration of methocarbamol in the horse.

    Science.gov (United States)

    Rumpler, M J; Colahan, P; Sams, R A

    2014-02-01

    A simple LC/MSMS method has been developed and fully validated to determine concentrations and characterize the concentration vs. time course of methocarbamol (MCBL) and guaifenesin (GGE) in plasma after a single intravenous dose and multiple oral dose administrations of MCBL to conditioned Thoroughbred horses. The plasma concentration-time profiles for MCBL after a single intravenous dose of 15 mg/kg of MCBL were best described by a three-compartment model. Mean extrapolated peak (C0 ) plasma concentrations were 23.2 (± 5.93) μg/mL. Terminal half-life, volume of distribution at steady-state, mean residence time, and systemic clearance were characterized by a median (range) of 2.96 (2.46-4.71) h, 1.05 (0.943-1.21) L/kg, 1.98 (1.45-2.51) h, and 8.99 (6.68-10.8) mL/min/kg, respectively. Oral dose of MCBL was characterized by a median (range) terminal half-life, mean transit time, mean absorption time, and apparent oral clearance of 2.89 (2.21-4.88) h, 2.67 (1.80-2.87) h, 0.410 (0.350-0.770) h, and 16.5 (13.0-20) mL/min/kg. Bioavailability of orally administered MCBL was characterized by a median (range) of 54.4 (43.2-72.8)%. Guaifenesin plasma concentrations were below the limit of detection in all samples collected after the single intravenous dose of MCBL whereas they were detected for up to 24 h after the last dose of the multiple-dose oral regimen. This difference may be attributed to first-pass metabolism of MCBL to GGE after oral administration and may provide a means of differentiating the two routes of administration. © 2013 John Wiley & Sons Ltd.

  19. Brexpiprazole Alters Monoaminergic Systems following Repeated Administration: an in Vivo Electrophysiological Study

    OpenAIRE

    Oosterhof, Chris A.; Mansari, Mostafa El; Bundgaard, Christoffer; Blier, Pierre

    2015-01-01

    Background: Brexpiprazole was recently approved as adjunctive therapy for depression and treatment of schizophrenia in adults. To complement results from a previous study in which its acute effects were characterized, the present study assessed the effect of repeated brexpiprazole administration on monoaminergic systems. Methods: Brexpiprazole (1mg/kg, subcutaneous) or vehicle was administered once daily for 2 and 14 days. Single-unit electrophysiological recordings from noradrenaline neurons...

  20. Transplantation of hematopoietic stem cells: intra-arterial versus intravenous administration impacts stroke outcomes in a murine model.

    Science.gov (United States)

    Kasahara, Yukiko; Yamahara, Kenichi; Soma, Toshihiro; Stern, David M; Nakagomi, Takayuki; Matsuyama, Tomohiro; Taguchi, Akihiko

    2016-10-01

    Based on results of hematopoietic stem cell transplantation in animal models of stroke, clinical trials with hematopoietic stem cells administered intra-arterially or intravenously have been initiated in patients. Although intra-arterial injection is expected to deliver transplanted cells more directly to the ischemic tissue, the optimal route for enhancing clinical outcomes has not been identified in the setting of stroke. In this study, we compared the therapeutic potential of intra-arterial versus intravenous injection of bone marrow derived-mononuclear cells (BM-MNCs) and CD133-positive (CD133(+)) cells in a murine stroke model. We have found that intra-arterial injection of BM-MNCs exaggerates inflammation with accompanying loss of microvascular structures in poststroke brain and no improvement in cortical function. In contrast, intravenous injection of BM-MNCs did not similarly enhance inflammation and improved cortical function. Our results indicate that the optimal route of cell transplantation can vary with different cell populations and highlight possible issues that might arise with intra-arterial cell administration for acute ischemic cerebrovascular disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. COMPARISON OF INTRAVENOUS MAGNESIUM AND PLACEBO ADMINISTRATION ON POSTOPERATIVE PAIN AND ANALGESIC CONSUMPTION DURING SPINAL ANESTHESIA FOR INGUINAL HERNIA REPAIR

    Directory of Open Access Journals (Sweden)

    Olapour A

    2013-06-01

    Full Text Available Previous studies have suggested that magnesium may be a useful adjuvant to postoperative analgesia. We investigated efficacy of intravenous infusion of magnesium sulfate during spinal anesthesia to reduce post-operative pain and opioid consumption in patients undergoing inguinal hernia surgery.We randomly divided one hundred patients’ age 18-55 years old and ASA class I-II undergoing inguinal surgery into two groups. The magnesium group (Group M received magnesium sulfate 50 mg/kg in 100 ml normal saline intravenously within 10 minutes and 15 mg/kg/h by continuous infusion during the operation in one hour. The control group (Group S received the same amount of normal saline without magnesium sulfate. All patients received spinal anesthesia. Postoperative pain scores, meperidine consumption, and motor block were evaluated during 24 hours after surgery.Postoperative pain scores were significantly lower in Group M at 2, 3, 4 and 6 hours after surgery (P<0.05. Motor block was longer in Group M (P<0.05. Cumulative postoperative meperidine consumptions were also significantly lower in Group M at 24 h after surgery (P<0.05. 12% nausea and 26% flashing have been reported in Group M. A bolus and intravenous infusion of magnesium sulfate administration during spinal anesthesia improves postoperative analgesia. IRCT201201088645N1.

  2. Elimination of progressive mammary cancer by repeated administrations of chimeric antigen receptor-modified T cells.

    Science.gov (United States)

    Globerson-Levin, Anat; Waks, Tova; Eshhar, Zelig

    2014-05-01

    Continuous oncogenic processes that generate cancer require an on-going treatment approach to eliminate the transformed cells, and prevent their further development. Here, we studied the ability of T cells expressing a chimeric antibody-based receptor (CAR) to offer a therapeutic benefit for breast cancer induced by erbB-2. We tested CAR-modified T cells (T-bodies) specific to erbB-2 for their antitumor potential in a mouse model overexpressing a human erbB-2 transgene that develops mammary tumors. Comparing the antitumor reactivity of CAR-modified T cells under various therapeutic settings, either prophylactic, prior to tumor development, or therapeutically. We found that repeated administration of CAR-modified T cells is required to eliminate spontaneously developing mammary cancer. Systemic, as well as intratumoral administered CAR-modified T cells accumulated at tumor sites and eventually eliminated the malignant cells. Interestingly, within a few weeks after a single CAR T cells' administration, and rejection of primary lesion, tumors usually relapsed both in treated mammary gland and at remote sites; however, repeated injections of CAR-modified T cells were able to control the secondary tumors. Since spontaneous tumors can arise repeatedly, especially in the case of syndromes characterized by specific susceptibility to cancer, multiple administrations of CAR-modified T cells can serve to control relapsing disease.

  3. Fentanyl Pharmacokinetics in Pregnant Sheep after Intravenous and Transdermal Administration to the Ewe.

    Science.gov (United States)

    Heikkinen, Emma M; Voipio, Hanna-Marja; Laaksonen, Sakari; Haapala, Linnea; Räsänen, Juha; Acharya, Ganesh; Erkinaro, Tiina; Haapsamo, Mervi; Hautajärvi, Heidi; Kokki, Hannu; Kokki, Merja; Heikkinen, Aki T

    2015-09-01

    Fentanyl is used for pain treatment during pregnancy in human beings and animals. However, fentanyl pharmacokinetics during pregnancy has not been fully established. The aim of this study was to characterize fentanyl pharmacokinetics in pregnant sheep after intravenous and transdermal dosing during surgical procedure performed to ewe and foetus. Pharmacokinetic parameters reported for non-pregnant sheep and nominal transdermal dose rate were utilized for a priori calculation to achieve analgesic fentanyl concentration (0.5-2 ng/ml) in maternal plasma. A total of 20 Aland landrace ewes at 118-127 gestational days were used. In the first protocol, 1 week before surgery, 10 animals received 2 μg/kg fentanyl intravenous bolus, and on the operation day, transdermal fentanyl patches at nominal dose rate of 2 μg/kg/hr were applied to antebrachium, and ewes were then given a 2 μg/kg intravenous bolus followed by an intra-operative 2.5 μg/kg/hr infusion. In the second protocol, 10 animals received fentanyl only as transdermal patches on the operation day and oxycodone for rescue analgesia. The data were analysed with population pharmacokinetic modelling. Intra- and post-operative fentanyl concentrations were similar and slightly lower than the a priori predictions, and elimination and distribution clearances appeared slower during than before or after the surgery. Transdermal patches provided sustained fentanyl absorption for up to 5 days, but the absorption rate was slower than the nominal dose rate and showed a high interindividual variability. Further research is warranted to evaluate the clinical relevance of the observations made in sheep.

  4. Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration

    Directory of Open Access Journals (Sweden)

    Shin Chang-Sik

    2011-09-01

    Full Text Available Abstract Artesunate (AS is a clinically versatile artemisinin derivative utilized for the treatment of mild to severe malaria infection. Given the therapeutic significance of AS and the necessity of appropriate AS dosing, substantial research has been performed investigating the pharmacokinetics of AS and its active metabolite dihydroartemisinin (DHA. In this article, a comprehensive review is presented of AS clinical pharmacokinetics following administration of AS by the intravenous (IV, intramuscular (IM, oral or rectal routes. Intravenous AS is associated with high initial AS concentrations which subsequently decline rapidly, with typical AS half-life estimates of less than 15 minutes. AS clearance and volume estimates average 2 - 3 L/kg/hr and 0.1 - 0.3 L/kg, respectively. DHA concentrations peak within 25 minutes post-dose, and DHA is eliminated with a half-life of 30 - 60 minutes. DHA clearance and volume average between 0.5 - 1.5 L/kg/hr and 0.5 - 1.0 L/kg, respectively. Compared to IV administration, IM administration produces lower peaks, longer half-life values, and higher volumes of distribution for AS, as well as delayed peaks for DHA; other parameters are generally similar due to the high bioavailability, assessed by exposure to DHA, associated with IM AS administration (> 86%. Similarly high bioavailability of DHA (> 80% is associated with oral administration. Following oral AS, peak AS concentrations (Cmax are achieved within one hour, and AS is eliminated with a half-life of 20 - 45 minutes. DHA Cmax values are observed within two hours post-dose; DHA half-life values average 0.5 - 1.5 hours. AUC values reported for AS are often substantially lower than those reported for DHA following oral AS administration. Rectal AS administration yields pharmacokinetic results similar to those obtained from oral administration, with the exceptions of delayed AS Cmax and longer AS half-life. Drug interaction studies conducted with oral AS

  5. Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration.

    Science.gov (United States)

    Morris, Carrie A; Duparc, Stephan; Borghini-Fuhrer, Isabelle; Jung, Donald; Shin, Chang-Sik; Fleckenstein, Lawrence

    2011-09-13

    Artesunate (AS) is a clinically versatile artemisinin derivative utilized for the treatment of mild to severe malaria infection. Given the therapeutic significance of AS and the necessity of appropriate AS dosing, substantial research has been performed investigating the pharmacokinetics of AS and its active metabolite dihydroartemisinin (DHA). In this article, a comprehensive review is presented of AS clinical pharmacokinetics following administration of AS by the intravenous (IV), intramuscular (IM), oral or rectal routes. Intravenous AS is associated with high initial AS concentrations which subsequently decline rapidly, with typical AS half-life estimates of less than 15 minutes. AS clearance and volume estimates average 2 - 3 L/kg/hr and 0.1 - 0.3 L/kg, respectively. DHA concentrations peak within 25 minutes post-dose, and DHA is eliminated with a half-life of 30 - 60 minutes. DHA clearance and volume average between 0.5 - 1.5 L/kg/hr and 0.5 - 1.0 L/kg, respectively. Compared to IV administration, IM administration produces lower peaks, longer half-life values, and higher volumes of distribution for AS, as well as delayed peaks for DHA; other parameters are generally similar due to the high bioavailability, assessed by exposure to DHA, associated with IM AS administration (> 86%). Similarly high bioavailability of DHA (> 80%) is associated with oral administration. Following oral AS, peak AS concentrations (Cmax) are achieved within one hour, and AS is eliminated with a half-life of 20 - 45 minutes. DHA Cmax values are observed within two hours post-dose; DHA half-life values average 0.5 - 1.5 hours. AUC values reported for AS are often substantially lower than those reported for DHA following oral AS administration. Rectal AS administration yields pharmacokinetic results similar to those obtained from oral administration, with the exceptions of delayed AS Cmax and longer AS half-life. Drug interaction studies conducted with oral AS suggest that AS does not

  6. Intravenous iron administration: new observations and time for the next steps.

    Science.gov (United States)

    Weiss, Günter; Kronenberg, Florian

    2015-01-01

    In this issue of Kidney International, the Dialysis Outcomes and Practice Patterns Study reports that hemodialysis patients with monthly intravenous iron supplementation of 300-399 mg or ⩾400 mg had a 13 or 18% higher risk of dying, respectively, compared with those receiving 100-199 mg per month, with no obvious differences in cause-specific mortalities. This study supports that randomized controlled trials are urgently needed to identify optimized iron supplementation strategies for anemic dialysis patients.

  7. Intravenous Administration of Endothelial Colony-Forming Cells Overexpressing Integrin β1 Augments Angiogenesis in Ischemic Legs.

    Science.gov (United States)

    Goto, Kazuko; Takemura, Genzou; Takahashi, Tomoyuki; Okada, Hideshi; Kanamori, Hiromitsu; Kawamura, Itta; Watanabe, Takatomo; Morishita, Kentaro; Tsujimoto, Akiko; Miyazaki, Nagisa; Ushikoshi, Hiroaki; Kawasaki, Masanori; Mikami, Atsushi; Kosai, Ken-ichiro; Minatoguchi, Shinya

    2016-02-01

    When injected directly into ischemic tissue in patients with peripheral artery disease, the reparative capacity of endothelial progenitor cells (EPCs) appears to be limited by their poor survival. We, therefore, attempted to improve the survival of transplanted EPCs through intravenous injection and gene modification. We anticipated that overexpression of integrin β1 will enable injected EPCs to home to ischemic tissue, which abundantly express extracellular matrix proteins, the ligands for integrins. In addition, integrin β1 has an independent angiogenesis-stimulating function. Human endothelial colony-forming cells (ECFCs; late-outgrowth EPCs) were transduced using a lentiviral vector encoding integrin β1 (ITGB1) or enhanced green fluorescent protein (GFP). We then locally or systemically injected phosphate-buffered saline or the genetically modified ECFCs (GFP-ECFCs or ITGB1-ECFCs; 1 × 10(5) cells each) into NOD/Shi-scid, IL-2Rγnull mice whose right femoral arteries had been occluded 24 hours earlier. Upregulation of extracellular matrix proteins, including fibronectin, was apparent in the ischemic legs. Four weeks later, blood perfusion of the ischemic limb was significantly augmented only in the ITGB1-ECFC group. Scanning electron microscopy of vascular casts revealed increases in the perfused blood vessels in the ischemic legs of mice in the ITGB1-ECFC group and significant increases in the density of both capillaries and arterioles. Transplanted ECFC-derived vessels accounted for 28% ± 4.2% of the vessels in the ITGB1-ECFC group, with no cell fusion. Intravenous administration of ECFCs engineered to home to ischemic tissue appears to efficiently mediate therapeutic angiogenesis in a mouse model of peripheral artery disease. Significance: The intravenous administration of endothelial colony-forming cells (ECFCs) genetically modified to overexpress integrin β1 effectively stimulated angiogenesis in ischemic mouse hindlimbs. Transplanted ECFCs were

  8. Effect of repeated oral administration on taurocholate on hepatic excretory function in the rat.

    Science.gov (United States)

    Watkins, J B; Klaassen, C D

    1981-07-01

    The effect of repeated administration of taurocholate on bile acid pool size, biliary composition and biliary excretory capacity for bile acids and two xenobiotics was determined. The bile acid pool was increased 50 to 60% by oral administration of sodium taurocholate (300--900 mg/kg, 10 ml/kg) every 12 hr for 2 days to male Sprague-Dawley rats. Bile flow, biliary excretion of bile acids, cholesterol and phospholipid and the concentrations of phospholipid and bile acids in bile were increased in rats treated with 750 mg of taurocholate per kg. No effect was observed on Na+,K+ or Cl- levels. The biliary transport maximum for taurocholate was increased by 30% in rats treated with 750 mg/kg. In contrast, the plasma disappearance and biliary excretion of phenol-3,6-dibromphthalein and ouabain were not affected by taurocholate administration.

  9. Development of a stable low-dose aglycosylated antibody formulation to minimize protein loss during intravenous administration

    Science.gov (United States)

    Morar-Mitrica, Sorina; Puri, Manasi; Beumer Sassi, Alexandra; Fuller, Joshua; Hu, Ping; Crotts, George; Nesta, Douglas

    2015-01-01

    The physical and chemical integrity of a biopharmaceutical must be maintained not only during long-term storage but also during administration. Specifically for the intravenous (i.v.) delivery of a protein drug, loss of stability can occur when the protein formulation is compounded with i.v. bag diluents, thus modifying the original composition of the drug product. Here we present the challenges associated with the delivery of a low-dose, highly potent monoclonal antibody (mAb) via the i.v. route. Through parallel in-use stability studies and conventional formulation development, a drug product was developed in which adsorptive losses and critical oxidative degradation pathways were effectively controlled. This development approach enabled the i.v. administration of clinical doses in the range of 0.1 to 0.5 mg total protein, while ensuring liquid drug product storage stability under refrigerated conditions. PMID:26073995

  10. Tissue disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and topical administration in rats.

    Science.gov (United States)

    Fediuk, Daryl J; Wang, Tao; Chen, Yufei; Parkinson, Fiona E; Namaka, Michael P; Simons, Keith J; Burczynski, Frank J; Gu, Xiaochen

    2011-10-01

    The insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone (OBZ) have been shown to produce synergistic permeation enhancement when applied concurrently in vitro and in vivo. The disposition of both compounds following intravenous administration (2 mg/kg of DEET or OBZ) and topical skin application (100 mg/kg of DEET and 40 mg/kg of OBZ) was determined in male Sprague-Dawley rats. Pharmacokinetic analysis was also conducted using compartmental and non-compartmental methods. A two-compartment model was deemed the best fit for intravenous administration. The DEET and oxybenzone permeated across the skin to accumulate in blood, liver and kidney following topical skin application. Combined use of DEET and oxybenzone accelerated the disappearance of both compounds from the application site, increased their distribution in the liver and significantly decreased the apparent elimination half-lives of both compounds (p < 0.05). Hepatoma cell studies revealed toxicity from exposure to all treatment concentrations, most notably at 72 h. Although DEET and oxybenzone were capable of mutually enhancing their percutaneous permeation and systemic distribution from topical skin application, there was no evidence of increased hepatotoxic deficits from concurrent application.

  11. Tissue distribution of borneol-modified ganciclovir-loaded solid lipid nanoparticles in mice after intravenous administration.

    Science.gov (United States)

    Ren, Jungang; Zou, Meijuan; Gao, Ping; Wang, Yue; Cheng, Gang

    2013-02-01

    The main purpose of this research was to prepare borneol-modified and non-borneol ganciclovir-loaded solid lipid nanoparticles (SLNs) to study whether borneol could enhance the transport of ganciclovir (GCV) incorporated in SLN to the brain in mice after their intravenous administration. Ganciclovir injection (GCV-inj) was selected as a control. The SLNs were prepared using a modified microemulsion method. Pharmacokinetic and biodistribution studies were conducted in kunming mice after intravenous administration of GCV-inj, GCV solid lipid nanoparticles without borneol (GCV-SLN), and three types of GCV solid lipid nanoparticles containing different ratios of borneol (GCVb-SLN). It was found that, in plasma, the area under the concentration-time curve (AUC 0 ∼ t) for GCVb-SLN and GCV-SLN was greater than that for the GCV-inj. In the brain, the AUC 0 ∼ t of GCVb-SLN was significantly increased compared with that of a GCV-inj and GCV-SLN. In the other mouse tissues, the peak concentration of GCV achieved was always lower after the injection of any of the four types of SLN than after the commercial injection. These results indicate that GCV-SLN modified with borneol enhances the transport of ganciclovir to the brain. Therefore, SLN modified with borneol is a potential delivery system for transporting drugs to the central nervous system (CNS).

  12. Pharmacokinetics and effects on thromboxane B2 production following intravenous administration of flunixin meglumine to exercised thoroughbred horses.

    Science.gov (United States)

    Knych, H K; Arthur, R M; McKemie, D S; Chapman, N

    2015-08-01

    Flunixin meglumine is commonly used in horses for the treatment of musculoskeletal injuries. The current ARCI threshold recommendation is 20 ng/mL when administered at least 24 h prior to race time. In light of samples exceeding the regulatory threshold at 24 h postadministration, the primary goal of the study reported here was to update the pharmacokinetics of flunixin following intravenous administration, utilizing a highly sensitive liquid chromatography-mass spectrometry (LC-MS). An additional objective was to characterize the effects of flunixin on COX-1 and COX-2 inhibition when drug concentrations reached the recommended regulatory threshold. Sixteen exercised adult horses received a single intravenous dose of 1.1 mg/kg. Blood samples were collected up to 72 h postadministration and analyzed using LC-MS. Blood samples were collected from 8 horses for determination of TxB(2) and PGE(2) concentrations prior to and up to 96 h postflunixin administration. Mean systemic clearance, steady-state volume of distribution and terminal elimination half-life was 0.767 ± 0.098 mL/min/kg, 0.137 ± 0.12 L/kg, and 4.8 ± 1.59 h, respectively. Four of the 16 horses had serum concentrations in excess of the current ARCI recommended regulatory threshold at 24 h postadministration. TxB(2) suppression was significant for up to 24 h postadministration.

  13. Pharmacokinetics, metabolism and urinary detection time of flunixin after intravenous administration in camels.

    Science.gov (United States)

    Wasfi, I A; Boni, N S; Abdel Hadi, A; Elghazali, M; Zorob, O; Alkatheeri, N A; Barezaiq, I M

    1998-06-01

    The pharmacokinetics of flunixin were determined after an intravenous dose of 1.1 mg/kg body weight in six camels and 2.2 mg/kg body weight in four camels. The data obtained (mean +/- SEM) for the low and high dose, respectively, were as follows: The elimination half-lives (t1/2 beta) were 3.76 +/- 0.24 and 4.08 +/- 0.49 h, the steady state volumes of distribution (Vdss) were 320.61 +/- 38.53 and 348.84 +/- 35.36 mL/kg body weight, total body clearances (ClT) were 88.96 +/- 6.63 and 84.86 +/- 4.95 mL/h/kg body weight and renal clearances (Clr) were 0.52 +/- 0.09 and 0.62 +/- 0.18 mL/h/kg body weight. A hydroxylated metabolite of flunixin was identified by gas chromatography/mass spectrometry (GC/MS) under electron and chemical ionization and its major fragmentation pattern was verified by tandem mass spectrometry (GC/MS/MS) using neutral loss, daughter and parent scan modes. The detection times for flunixin and its hydroxylated metabolite in urine after an intravenous (i.v.) dose of 2.2 mg/kg body weight were 96 and 48 h, respectively.

  14. Disposition kinetics of a dipeptide ester prodrug of acyclovir and its metabolites following intravenous and oral administrations in rat.

    Science.gov (United States)

    Talluri, Ravi S; Gaudana, Ripal; Hariharan, Sudharshan; Jain, Ritesh; Mitra, Ashim K

    2009-01-01

    The objective of this work was to study the disposition kinetics of valine-valine-acyclovir (VVACV), a dipeptide ester prodrug of acyclovir following intravenous and oral administrations in rat. A validated LC-MS/MS analytical method was developed for the analysis VVACV, Valine-Acyclovir (VACV), and Acyclovir (ACV) using a linear Ion Trap Quadrupole. ACV was administered orally for comparison purpose. In the VVACV group, both blood and urine samples and in the ACV group only blood samples were collected. All the samples were analyzed using LC-MS/MS. The LLOQ for ACV, VACV, and VVACV were 10, 10, and 50 ng/ml, respectively. Relevant pharmacokinetic parameters were obtained by non-compartmental analyses of data with WinNonlin. Following i.v. administration of VVACV, AUC(0-inf) (min*µM) values for VVACV, VACV, and ACV were 55.06, 106, and 466.96, respectively. The AUC obtained after oral administration of ACV was 178.8. However, following oral administration of VVACV, AUC(0-inf) values for VACV and ACV were 89.28 and 810.77, respectively. Thus the exposure of ACV obtained following oral administration of VVACV was almost 6-fold higher than ACV. This preclinical pharmacokinetic data revealed that VVACV has certainly improved the oral bioavailability of ACV and is an effective prodrug for oral delivery of ACV.

  15. Pharmacokinetic evaluation of Shenfu Injection in beagle dogs after intravenous drip administration

    Directory of Open Access Journals (Sweden)

    Yuqiao Zhang

    2016-10-01

    Full Text Available Shenfu Injection (SFI is a well-defined Chinese herbal formulation that is obtained from red ginseng and processed aconite root. The main active constituents in SFI are ginsenosides and aconitum alkaloids. In this work, ginsenosides (ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Rc and aconitum alkaloids (benzoylmesaconine and fuziline were used as the index components to explore the pharmacokinetic behavior of SFI. A selective and sensitive HPLC–MS/MS method was developed for the quantification of ginsenosides and aconitum alkaloids in dog plasma and was used to characterize the pharmacokinetics of the five index components after intravenous drip of three different dosages of SFI in beagle dogs. The pharmacokinetic properties of the index components were linear over the dose range of 2–8 mL/kg.

  16. Pharmacokinetic evaluation of Shenfu Injection in beagle dogs after intravenous drip administration.

    Science.gov (United States)

    Zhang, Yuqiao; Tian, Dali; Huang, Yuyou; Li, Ling; Mao, Juan; Tian, Juan; Ding, Jinsong

    2016-11-01

    Shenfu Injection (SFI) is a well-defined Chinese herbal formulation that is obtained from red ginseng and processed aconite root. The main active constituents in SFI are ginsenosides and aconitum alkaloids. In this work, ginsenosides (ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Rc) and aconitum alkaloids (benzoylmesaconine and fuziline) were used as the index components to explore the pharmacokinetic behavior of SFI. A selective and sensitive HPLC-MS/MS method was developed for the quantification of ginsenosides and aconitum alkaloids in dog plasma and was used to characterize the pharmacokinetics of the five index components after intravenous drip of three different dosages of SFI in beagle dogs. The pharmacokinetic properties of the index components were linear over the dose range of 2-8 mL/kg.

  17. Absence of analgesic effect of intravenous melatonin administration during daytime after laparoscopic cholecystectomy

    DEFF Research Database (Denmark)

    Andersen, Lars Peter Holst; Kücükakin, Bülent; Werner, Mads U

    2014-01-01

    STUDY OBJECTIVE: To investigate whether melatonin administered intraoperatively reduced pain following laparoscopic cholecystectomy. DESIGN: Randomized, placebo-controlled, double-blinded study. SETTING: Two surgical departments in Copenhagen. PATIENTS: 44 women between 18 and 70 years of age, who...... mg of intravenous (IV) melatonin or placebo were administered at the time of surgical incision. MEASUREMENTS: Pain was assessed by a set of questionnaires documenting "pain at rest" using a visual analog scale (VAS). The use of rescue medication was recorded. Sleep quality and general well-being were...... between the two groups in the postoperative period. The use of postoperative rescue medication did not differ between the groups. CONCLUSIONS: The use of 10mg of IV melatonin administered during laparoscopic cholecystectomy did not affect postoperative pain or use of analgesic medication....

  18. Effects of nicotine gum on repeated administration of the Stroop test.

    Science.gov (United States)

    Provost, S C; Woodward, R

    1991-01-01

    Using a double-blind procedure, 24 non-smoking subjects chewed either 2 mg nicorette gum or a placebo for 20 min, before completing a Stroop test on three occasions. Colour-word reading and simple colour naming times were consistent across repeats, and were unaffected by nicotine. However, the time taken to name the colour of incongruous colour word stimuli declined across trials. This increase in speed across repeats was significantly greater in those subjects who had received nicotine. These data are consistent with previous reports of a decreased Stroop effect following nicotine administration, but are not compatible with a simple model which assumes that nicotine alters the way in which information is filtered by selective attentional mechanisms. The present results can be explained by postulating that nicotine influences either the rate at which colour naming become more automatic, or changes the way in which resources are allocated to non-automatic processes.

  19. Pharmacokinetics and pharmacodynamics of midazolam following intravenous and intramuscular administration to sheep.

    Science.gov (United States)

    Simon, Bradley T; Scallan, Elizabeth M; O, Odette; Ebner, Lisa Sams; Cerullo, Michelle N; Follette, Christelle; Cox, Sherry K; Doherty, Thomas J; Lizarraga, Ignacio

    2017-05-01

    OBJECTIVE To determine the pharmacokinetic and pharmacodynamic effects of midazolam following IV and IM administration in sheep. ANIMALS 8 healthy adult rams. PROCEDURES Sheep were administered midazolam (0.5 mg/kg) by the IV route and then by the IM route 7 days later in a crossover study. Physiologic and behavioral variables were assessed and blood samples collected for determination of plasma midazolam and 1-hydroxymidazolam (primary midazolam metabolite) concentrations immediately before (baseline) and at predetermined times for 1,440 minutes after midazolam administration. Pharmacokinetic parameters were calculated by compartmental and noncompartmental methods. RESULTS Following IV administration, midazolam was rapidly and extensively distributed and rapidly eliminated; mean ± SD apparent volume of distribution, elimination half-life, clearance, and area under the concentration-time curve were 838 ± 330 mL/kg, 0.79 ± 0.44 hours, 1,272 ± 310 mL/h/kg, and 423 ± 143 h·ng/mL, respectively. Following IM administration, midazolam was rapidly absorbed and bioavailability was high; mean ± SD maximum plasma concentration, time to maximum plasma concentration, area under the concentration-time curve, and bioavailability were 820 ± 268 ng/mL, 0.46 ± 0.26 hours, 1,396 ± 463 h·ng/mL, and 352 ± 148%, respectively. Respiratory rate was transiently decreased from baseline for 15 minutes after IV administration. Times to peak sedation and ataxia after IV administration were less than those after IM administration. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated midazolam was a suitable short-duration sedative for sheep, and IM administration may be a viable alternative when IV administration is not possible.

  20. Huperzine A inhibits immediate addictive behavior but not behavioral sensitization following repeated morphine administration in rats.

    Science.gov (United States)

    Sun, Jinling; Tian, Lin; Cui, Ruisi; Li, Xinwang

    2017-04-01

    Acetylcholinesterase inhibitors are regarded as promising therapeutic agents to treat addiction. The current study aimed to examine the effects of huperzine A, a cholinesterase inhibitor, on behavioral sensitization induced by repeated morphine administration and relapse induced by contextual conditioning. The present study also assessed whether the state-dependency hypothesis may explain the results. Adult rats were divided into four groups (n=8) and intraperitoneally injected with 0.2, 0.3 or 0.4 mg/kg huperzine A or saline (1 ml/kg, control), for 5 days. The effect of repeated huperzine A administration alone on locomotor activity was assessed. For the experiments that analyzed the development of morphine-induced sensitization, 40 rats were divided into five groups (n=8): Saline+Saline, Saline+Morphine, 0.2, 0.3 and 0.4 mg/kg huperzine A+Morphine. Following a withdrawal period of 7 days, all animals were administered saline or morphine, as appropriate. To test the state-dependency hypothesis, the rats in the Saline+Morphine group were injected with saline and morphine, while the other three groups were administered different doses of huperzine A and morphine. To examine the effect of huperzine A on the expression of morphine-induced sensitization, the rats in huperzine A+Morphine groups were injected with appropriate concentrations of huperzine A, and morphine. The current results indicated that the administration of huperzine A alone did not affect locomotor activity, while higher doses of huperzine A inhibited the addictive behavior induced by morphine at the development phase. Additionally, huperzine A administration during the expression phase of morphine sensitization did not inhibit the relapse induced by administration of saline. Furthermore, 0.4 mg/kg huperzine A inhibited the expression of morphine-induced behavioral sensitization. Therefore, the results of the current study do not support the state-dependency hypothesis.

  1. Repeated administration of imipramine modifies GABAergic transmission in rat frontal cortex.

    Science.gov (United States)

    Wabno, Joanna; Hess, Grzegorz

    2013-05-01

    Alterations in the functions of brain gamma-aminobutyric acid (GABA) inhibitory system and a distortion in the balance between excitatory and inhibitory synaptic transmission have been hypothesized to be possible causes of mood disorders. Experimental evidence points to modifications of GABAergic transmission as a result of prolonged treatment with antidepressant drugs, however, the influence of the tricyclic antidepressant imipramine on inhibitory synaptic transmission in the rat cerebral cortex has not yet been investigated. Therefore, in the present study the effects of single and repeated administration of imipramine were evaluated ex vivo in slices of the rat frontal cortex using electrophysiological approach. In slices prepared 2 days after the last drug administration from animals receiving imipramine for 14 days (dose 10 mg/kg p.o., twice daily) the mean frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from layer II/III pyramidal neurons was decreased, while the mean amplitude of sIPSCs was increased. These effects were absent in slices obtained from rats which received imipramine once. Application of N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN 082), a selective mGluR7 allosteric agonist, to the slice incubation medium resulted in a decrease in the mean frequency of sIPSCs in preparations obtained from repeated imipramine-treated animals, in contrast to slices originating from control rats where no AMN 082-induced effects were observed. Repeated imipramine treatment reduced protein density levels of the three tested GABAA receptor subunits: α 1, β 2 and γ 2. These data indicate that repeated treatment of normal rats with imipramine results in a modification of the release mechanism of GABA from presynaptic terminals and its modulation by mGluR7 receptors as well as in an alteration in GABAA receptor subunit protein levels in the rat cerebral cortex.

  2. Intravenous administration of a polyionic solution containing 84 mEq/l of lactate resolves experimentally induced hyperchloraemic acidosis in horses.

    Science.gov (United States)

    Romão, F T N M A; Pereira, P F V; Flaiban, K K M C; Dearo, A C O; Fernandes, T M; Lisbôa, J A N

    2017-01-01

    Treatment of metabolic acidosis using sodium bicarbonate solutions is safe when blood gas analysis is available. The evidence that solutions containing metabolisable buffers can be used as an alternative for treatment of metabolic acidosis in horses is of practical interest. To investigate the safety and efficacy of a polyionic solution containing 84 mEq/l of lactate (L84) for the correction of induced hyperchloraemic metabolic acidosis. Non-randomised crossover design. Five healthy, adult, crossbred horses were used. A solution containing 100 mmol/l of HCl was infused intravenously (100 ml/kg bwt) for 5 h to induce metabolic acidosis. Metabolic acidosis was induced in each horse twice, with a minimum 15-day interval after recovery from the first induction: the first time no treatment was administered (control group) and the second time horses were treated with an intravenous infusion of L84 solution, 100 ml/kg bwt for 5 h, beginning 3 h after the end of HCl infusion. Venous blood samples were taken at 0, 2.5, 5, 8, 10.5, 13, 24 and 48 h; and urine at 0, 5, 8 and 13 h. Laboratory data included pH (blood and urine), PCO2 , HCO3(-) , base excess, total plasma protein concentration, l-lactate, Na(+) , K(+) , Cl(-) , strong ion difference (SID4 ), anion gap, change in plasma volume and fractional excretions of Na(+) , K(+) and Cl(-) . Effects of time and treatment were tested by 2-way repeated measures ANOVA. Severe hyperchloraemic metabolic acidosis was induced. In the untreated horses, correction of the imbalance occurred gradually, and mild acidosis was still present at 48 h. In horses treated with the L84 solution, acidosis was corrected by the end of the infusion. There were no adverse effects with the administration of the L84 solution. A polyionic solution containing 84 mEq/l of lactate effectively corrected induced metabolic acidosis in horses within 5 h. © 2015 EVJ Ltd.

  3. Pharmacokinetics of doxycycline in tilapia (Oreochromis aureus × Oreochromis niloticus) after intravenous and oral administration.

    Science.gov (United States)

    Yang, F; Li, Z L; Shan, Q; Zeng, Z L

    2014-08-01

    The pharmacokinetics of doxycycline was studied in plasma after a single dose (20 mg/kg) of intravenous or oral administration to tilapia (Oreochromis aureus × Oreochromis niloticus) reared in fresh water at 24 °C. Plasma samples were collected from six fish per sampling point. Doxycycline concentrations were determined by high-performance liquid chromatography with a 0.005 μg/mL limit of detection, then were subjected to noncompartmental analysis. Following oral administration, the double-peak phenomenon was observed, and the first (Cmax1 ) and second (Cmax2) peaks were 1.99 ± 0.43 μg/mL at 2.0 h and 2.27 ± 0.38 μg/mL at 24.0 h, respectively. After the intravenous injection, a Cmax2 (12.12 ± 1.97 μg/mL) was also observed, and initial concentration of 45.76 μg/mL, apparent elimination rate constant (λz) of 0.018 per h, apparent elimination half-life (t1/2λz) of 39.0 h, systemic total body clearance (Cl) of 41.28 mL/h/kg, volume of distribution (Vz) of 2323.21 mL/kg, and volume of distribution at steady-state (Vss) of 1356.69 mL/kg were determined, respectively. While after oral administration, the λz, t1/2λz, and bioavailability of doxycycline were 0.009 per h, 77.2 h, and 23.41%, respectively. It was shown that doxycycline was relatively slowly and incompletely absorbed, extensively distributed, and slowly eliminated in tilapia, in addition, doxycycline might undergo enterohepatic recycling in tilapia.

  4. Influence of Pasteurella multocida infection on the pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in rabbits.

    Science.gov (United States)

    Abo-el-Sooud, K; Goudah, A

    2010-02-01

    The pharmacokinetic behavior of marbofloxacin was studied in healthy (n = 12) and Pasteurella multocida infected rabbits (n = 12) after single intravenous (i.v.) and intramuscular (i.m.) administrations. Six rabbits in each group (control and diseased) were given a single dose of 2 mg/kg body weight (bw) of marbofloxacin intravenously. The other six rabbits in each group were given the same dose of the drug intramuscularly. The concentration of marbofloxacin in plasma was determined using high-performance liquid chromatography. The plasma concentrations were higher in diseased rabbits than in healthy rabbits following both routes of injections. Following i.v. administration, the values of the elimination half-life (t(1/2beta)), and area under the curve were significantly higher, whereas total body clearance was significantly lower in diseased rabbits. After i.m. administration, the elimination half-life (t(1/2el)), mean residence time, and maximum plasma concentration (C(max)) were higher in diseased rabbits (5.33 h, 7.35 h and 2.24 microg/mL) than in healthy rabbits (4.33 h, 6.81 h and 1.81 microg/mL, respectively). Marbofloxacin was bound to the extent of 26 +/- 1.3% and 23 +/- 1.6% to plasma protein of healthy and diseased rabbits, respectively. The C(max)/MIC (minimum inhibitory concentration) and AUC/MIC ratios were significantly higher in diseased rabbits (28 and 189 h) than in healthy rabbits (23 and 157 h), indicating the favorable pharmacodynamic characteristics of the drug in diseased rabbits.

  5. Toxicity assessment of repeated intravenous injections of arginine–glycine–aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice

    Directory of Open Access Journals (Sweden)

    Wang YW

    2014-10-01

    Full Text Available You-Wei Wang, Kai Yang, Hong Tang, Dan Chen, Yun-Long Bai Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Background: Nanotechnology-based near-infrared quantum dots (NIR QDs have many excellent optical properties, such as high fluorescence intensity, good fluorescence stability, and strong tissue-penetrating ability. Integrin αvß3 is highly and specifically expressed in tumor angiogenic vessel endothelial cells of almost all carcinomas. Recent studies have shown that NIR QDs linked to peptides containing the arginine–glycine–aspartic acid (RGD sequence (NIR QDs-RGD can specifically target integrin αvß3 expressed in endothelial cells of tumor angiogenic vessels in vivo, and they offer great potential for early cancer diagnosis, in vivo tumor imaging, and tumor individualized therapy. However, the toxicity profile of NIR QDs-RGD has not been reported. This study was conducted to investigate the toxicity of NIR QDs-RGD when intravenously administered to mice singly and repeatedly at the dose required for successful tumor imaging in vivo.Materials and methods: A NIR QDs-RGD probe was prepared by linking NIR QDs with the maximum emission wavelength of 800 nm (QD800 to the RGD peptide (QD800-RGD. QD800-RGD was intravenously injected to BALB/C mice once or twice (200 pmol equivalent of QD800 for each injection. phosphate-buffered saline solution was used as control. Fourteen days postinjection, toxicity tests were performed, including complete blood count (white blood cell, red blood cell, hemoglobin, platelets, lymphocytes, and neutrophils and serum biochemical analysis (total protein, albumin, albumin/globulin, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen. The coefficients of liver, spleen, kidney, and lung weight to body weight were measured, as well as their oxidation and antioxidation indicators, including

  6. Persistence and accumulation of micronucleated hepatocytes in liver of rats after repeated administration of diethylnitrosamine.

    Science.gov (United States)

    Narumi, Kazunori; Ashizawa, Koji; Fujiishi, Yohei; Tochinai, Ryota; Okada, Emiko; Tsuzuki, Yasuhiro; Tatemoto, Hideki; Hamada, Shuichi; Kaneko, Kimiyuki; Ohyama, Wakako

    2013-08-15

    A repeat-dose micronucleus assay in adult rat liver was recently developed [Mutat. Res. 747 (2012) 234-239]. This assay demonstrated a high detectability of hepatocarcinogens at relatively low doses, as indicated by dose-dependent micronucleus induction. Because the adult rat liver is known to have a long life-span, this desirable property of the assay will be an advantage in detecting micronucleated hepatocytes (MNHEPs) that have persisted for long periods in the liver following repeated dosing. However, no data directly supporting the underlying mechanisms have been published to date. In the present study, we verified the mechanisms by means of pulse-labeling of micronucleated hepatocytes with the thymidine analog 5-ethynyl-2'-deoxyuridine (EdU). The rodent hepatocarcinogen diethylnitrosamine (DEN) was repeatedly administered orally to male Crl:CD (SD) rats (6 weeks old) for up to 2 weeks, and EdU was injected intraperitoneally on days 1, 7, or 14. Hepatocytes were isolated by use of a non-perfusion technique at 24h, 1 week, or 2 weeks after EdU injection and analyzed for EdU incorporation and micronucleus formation. The results of our study confirmed that MNHEPs labeled with EdU on the first day of DEN administration persisted until 2 weeks post-administration in the rat livers. However, the frequency of MHNEPs among EdU-labeled hepatocytes decreased over time. In addition, the number of terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL)-positive cells in the liver tissue increased, suggesting selective removal of micronucleated cells. Theoretical calculation of the cumulative MNHEP frequency on each of the days on which DEN was administered, taking into account the rate of loss, came out closer to the actual value observed in the liver micronucleus test. Taken together, these results indicate that although micronucleated cells induced in rat livers by administration of the genotoxic hepatocarcinogen DEN undergo selective removal, they

  7. Morphine Analgesia Modification in Normotensive and Hypertensive Female Rats after Repeated Fluoxetine Administration.

    Science.gov (United States)

    Kosiorek-Witek, Anna; Makulska-Nowak, Helena Elżbieta

    2016-01-01

    The purpose of this investigation was to determine through the use of fluoxetine the effect of administering a serotonin reuptake inhibitor over several days on the antinociceptive action of μ-morphine type opioid receptor agonist. Investigations were performed on rats of both sexes, both the WKY normotensive strains as well as on the SHR genetically conditioned hypertensive strains. Results showed that the efficacy of morphine analgesia is higher in the SHR strain compared to normotensive rats (WKY). Surprisingly, repeated administration of fluoxetine reduced morphine analgesia, with the weakening of opioid antinociceptive action comparable to the duration of serotonin reuptake inhibitor administration. It was also concluded that the antinociceptive action of morphine in female rats and the alteration of its efficacy as a result of fluoxetine premedication for several days depend on oestrus cycle phase. The highest sensitivity of female rats to morphine was reported in the dioestrus and oestrus phases; much lower values were reported for the metoestrus phase.

  8. Antinociceptive effects of tramadol in co-administration with metamizol after single and repeated administrations in rats.

    Science.gov (United States)

    Moreno-Rocha, Luis Alfonso; Domínguez-Ramírez, Adriana Miriam; Cortés-Arroyo, Alma Rosa; Bravo, Guadalupe; López-Muñoz, Francisco Javier

    2012-11-01

    Combinations of two analgesic drugs of the same or different class are widely used in clinical therapy to enhance its antinociceptive effects and reduce the side effects. In order to evaluate a possible antinociceptive synergistic interaction of metamizol s.c., a nonsteroidal antiinflammatory drug (NSAID), and tramadol s.c., an atypical opioid (opioid receptor agonist), were administered alone or in combination. In the present study, the antinociceptive efficacy and the possible development of pharmacological tolerance produced by the combination tramadol plus metamizol during a 4-day treatment in rats using the plantar test was evaluated. Male Wistar rats were s.c. injected with tramadol (17.8 mg/kg), metamizol (177.8 mg/kg) or the combination tramadol plus metamizol three times a day for 4 days. Both metamizol and tramadol produced antinociceptive effects with a low rate trend towards tolerance development at the end of the treatment. The antinociceptive efficacy of tramadol and metamizol co-administration gradually decreased after the second injection. These data suggest that when the combination is given in a unique administration it results in an important potentiation of their individual antinociceptive effects. But, the repeated coadministration of tramadol plus metamizol results in a development of tolerance.

  9. Neuroimmunomodulatory effects of transcranial laser therapy combined with intravenous tPA administration for acute cerebral ischemic injury

    Institute of Scientific and Technical Information of China (English)

    Philip V. Peplow

    2015-01-01

    At present, the only FDA approved treatment for ischemic strokes is intravenous administration of tissue plasminogen activator within 4.5 hours of stroke onset. Owing to this brief window only a small percentage of patients receive tissue plasminogen activator. Transcranial laser therapy has been shown to be effective in animal models of acute ischemic stroke, resulting in signiifcant improvement in neurological score and function. NEST-1 and NEST-2 clinical trials in human patients have demonstrated the safety and positive trends in efifcacy of transcranial laser therapy for the treatment of ischemic stroke when initiated close to the time of stroke onset. Combining intravenous tissue plasminogen activator treatment with transcranial laser therapy may provide better functional outcomes. Statins given within 4 weeks of stroke onset improve stroke out-comes at 90 days compared to patients not given statins, and giving statins following transcranial laser therapy may provide an effective treatment for patients not able to be given tissue plasmin-ogen activator due to time constraints.

  10. PHARMACOKINETIC EVALUATION OF MELOXICAM AFTER INTRAVENOUS AND INTRAMUSCULAR ADMINISTRATION IN NILE TILAPIA (OREOCHROMIS NILOTICUS).

    Science.gov (United States)

    Fredholm, Daniel V; Mylniczenko, Natalie D; KuKanich, Butch

    2016-09-01

    Critically evaluating the pharmacokinetic behavior of a drug in the body provides crucial information about how to effectively treat a patient. Pharmacokinetic studies that exist in fish have primarily focused on drugs used to treat infectious disease, with minimal attention given to analgesic drugs. The objective of this study was to determine the pharmacokinetics of meloxicam (1 mg/kg) in Nile tilapia ( Oreochromis niloticus ) (n = 12). A single dose of meloxicam was administered either i.v. or i.m. Blood samples were obtained at predetermined times after drug injection. Plasma meloxicam concentrations were determined by a validated liquid chromatography/mass spectrometry method, and noncompartmental pharmacokinetic analysis was performed. The mean peak plasma concentration after i.m. injection was 1.95 μg/ml. The mean terminal half-life of meloxicam after i.v. and i.m. administration was 1.36 and 1.8 hr, respectively. The area under the plasma concentration-versus-time curve extrapolated to infinity was 11.26 hr·μg/ml after i.v. administration and 5.72 hr·μg/ml after i.m. administration. Bioavailability of meloxicam after i.m. administration was approximately half that of i.v. administration. Elimination was rapid in both the i.m. and i.v. routes of administration, suggesting that maintaining clinically relevant plasma concentrations may be difficult using this dose. This study represents the first pharmacokinetic evaluation of a nonsteroidal anti-inflammatory drug in a fish species, and further studies evaluating efficacy are needed.

  11. An AMS method to determine analyte recovery from pharmacokinetic studies with concomitant extravascular and intravenous administration.

    Science.gov (United States)

    Lappin, Graham; Seymour, Mark; Young, Graeme; Higton, David; Hill, Howard M

    2011-02-01

    The absolute bioavailability, clearance and volume of distribution of a drug can be investigated by administering a very low dose of the (14)C-drug intravenously along with a therapeutic nonlabeled dose by the extravascular route (typically orally). The total drug concentration is measured by an assay such as LC-MS and the (14)C-drug is measured by accelerator MS (AMS). In another article in this issue, a method validation is proposed where AMS was used as the analytical assay. Part of the validation is to assess the recovery of the analyte being measured as this has a direct impact on its quantification. In this article, a method of internal standardisation is described where the UV response of the nonlabeled analyte, spiked in excess into the matrix being analysed, is used for internal standardization. The method allows for the recovery of analyte to be measured in each individual sample being analysed. It is important to know the recovery of a (14)C-labeled analyte when determining its mass concentration from (14)C:(12)C isotopic ratio data using AMS. A method is reported in this article that utilizes the UV response of the nonlabeled drug for internal standardization, so that the recovery for each individual sample analyzed can be ascertained.

  12. Cerebral Microvascular and Systemic Effects Following Intravenous Administration of the Perfluorocarbon Emulsion Perftoran

    Directory of Open Access Journals (Sweden)

    Rania Abutarboush

    2016-11-01

    Full Text Available Oxygen-carrying perfluorocarbon (PFC fluids have the potential to increase tissue oxygenation during hypoxic states and to reduce ischemic cell death. Regulatory approval of oxygen therapeutics was halted due to concerns over vasoconstrictive side effects. The goal of this study was to assess the potential vasoactive properties of Perftoran by measuring brain pial arteriolar diameters in a healthy rat model. Perftoran, crystalloid (saline or colloid (Hextend solutions were administered as four sequential 30 min intravenous (IV infusions, thus allowing an evaluation of cumulative dose-dependent effects. There were no overall changes in diameters of small-sized (<50 μm pial arterioles within the Perftoran group, while both saline and Hextend groups exhibited vasoconstriction. Medium-sized arterioles (50–100 μm showed minor (~8–9% vasoconstriction within saline and Hextend groups and only ~5% vasoconstriction within the Perftoran group. For small- and medium-sized pial arterioles, the mean percent change in vessel diameters was not different among the groups. Although there was a tendency for arterial blood pressures to increase with Perftoran, pressures were not different from the other two groups. These data show that Perftoran, when administered to healthy anesthetized rats, does not cause additional vasoconstriction in cerebral pial arterioles or increase systemic blood pressure compared with saline or Hextend.

  13. Cerebral Microvascular and Systemic Effects Following Intravenous Administration of the Perfluorocarbon Emulsion Perftoran

    Science.gov (United States)

    Abutarboush, Rania; Saha, Biswajit K.; Mullah, Saad H.; Arnaud, Francoise G.; Haque, Ashraful; Aligbe, Chioma; Pappas, Georgina; Auker, Charles R.; McCarron, Richard M.; Moon-Massat, Paula F.; Scultetus, Anke H.

    2016-01-01

    Oxygen-carrying perfluorocarbon (PFC) fluids have the potential to increase tissue oxygenation during hypoxic states and to reduce ischemic cell death. Regulatory approval of oxygen therapeutics was halted due to concerns over vasoconstrictive side effects. The goal of this study was to assess the potential vasoactive properties of Perftoran by measuring brain pial arteriolar diameters in a healthy rat model. Perftoran, crystalloid (saline) or colloid (Hextend) solutions were administered as four sequential 30 min intravenous (IV) infusions, thus allowing an evaluation of cumulative dose-dependent effects. There were no overall changes in diameters of small-sized (<50 μm) pial arterioles within the Perftoran group, while both saline and Hextend groups exhibited vasoconstriction. Medium-sized arterioles (50–100 μm) showed minor (~8–9%) vasoconstriction within saline and Hextend groups and only ~5% vasoconstriction within the Perftoran group. For small- and medium-sized pial arterioles, the mean percent change in vessel diameters was not different among the groups. Although there was a tendency for arterial blood pressures to increase with Perftoran, pressures were not different from the other two groups. These data show that Perftoran, when administered to healthy anesthetized rats, does not cause additional vasoconstriction in cerebral pial arterioles or increase systemic blood pressure compared with saline or Hextend. PMID:27869709

  14. Brain targeting effect of camptothecin-loaded solid lipid nanoparticles in rat after intravenous administration.

    Science.gov (United States)

    Martins, Susana M; Sarmento, Bruno; Nunes, Cláudia; Lúcio, Marlene; Reis, Salette; Ferreira, Domingos C

    2013-11-01

    This study intended to investigate the ability of solid lipid nanoparticles (SLN) to deliver camptothecin into the brain parenchyma after crossing the blood-brain barrier. For that purpose, camptothecin-loaded SLN with mean size below 200 nm, low polydispersity index (94%) were produced. Synchrotron small and wide angle X-ray scattering (SAXS/WAXS) analysis indicates that SLN maintain their physical stability in contact with DMPC membrane, whereas SLN change the lamellar structure of DMPC into a cubic phase, which is associated with efficient release of the incorporated drugs. Cytotoxicity studies against glioma and macrophage human cell lines revealed that camptothecin-loaded SLN induced cell death with the lowest maximal inhibitory concentration (IC50) values, revealing higher antitumour activity of camptothecin-loaded SLN against gliomas. Furthermore, in vivo biodistribution studies of intravenous camptothecin-loaded SLN performed in rats proved the positive role of SLN on the brain targeting since significant higher brain accumulation of camptothecin was observed, compared to non-encapsulated drug. Pharmacokinetic studies further demonstrated lower deposition of camptothecin in peripheral organs, when encapsulated into SLN, with consequent decrease in potential side toxicological effects. These results confirmed the potential of camptothecin-loaded SLN for antitumour brain treatments.

  15. Roux-en-Y gastric bypass increases intravenous ethanol self-administration in dietary obese rats.

    Directory of Open Access Journals (Sweden)

    James E Polston

    Full Text Available Roux-en-Y gastric bypass surgery (RYGB is an effective treatment for severe obesity. Clinical studies however have reported susceptibility to increased alcohol use after RYGB, and preclinical studies have shown increased alcohol intake in obese rats after RYGB. This could reflect a direct enhancement of alcohol's rewarding effects in the brain or an indirect effect due to increased alcohol absorption after RGYB. To rule out the contribution that changes in alcohol absorption have on its rewarding effects, here we assessed the effects of RYGB on intravenously (IV administered ethanol (1%. For this purpose, high fat (60% kcal from fat diet-induced obese male Sprague Dawley rats were tested ~2 months after RYGB or sham surgery (SHAM using both fixed and progressive ratio schedules of reinforcement to evaluate if RGYB modified the reinforcing effects of IV ethanol. Compared to SHAM, RYGB rats made significantly more active spout responses to earn IV ethanol during the fixed ratio schedule, and achieved higher breakpoints during the progressive ratio schedule. Although additional studies are needed, our results provide preliminary evidence that RYGB increases the rewarding effects of alcohol independent of its effects on alcohol absorption.

  16. Detection of Progeny Immune Responses after Intravenous Administration of DNA Vaccine to Pregnant Mice

    Directory of Open Access Journals (Sweden)

    Xin Ke-Qin

    2002-01-01

    Full Text Available A number of factors influence the development of tolerance, including the nature, concentration and mode of antigen presentation to the immune system, as well as the age of the host. The studies were conducted to determine whether immunizing pregnant mice with liposome-encapsulated DNA vaccines had an effect on the immune status of their offspring. Two different plasmids (encoding antigens from HIV-1 and influenza virus were administered intravenously to pregnant mice. At 9.5 days post conception with cationic liposomes, injected plasmid was present in the tissues of the fetus, consistent with trans-placental transfer. When the offspring of vaccinated dams were immunized with DNA vaccine, they mounted stronger antigen-specific immune responses than controls and were protected against challenge by homologous influenza virus after vaccination. Moreover, such immune responses were strong in the offspring of mothers injected with DNA plasmid 9.5 days after coitus. These results suggest that DNA vaccinated mothers confer the antigen-specific immunity to their progeny. Here we describe the methods in detail as they relate to our previously published work.

  17. Alteration in metabolism and toxicity of acetaminophen upon repeated administration in rats.

    Science.gov (United States)

    Kim, Sun J; Lee, Min Y; Kwon, Do Y; Kim, Sung Y; Kim, Young C

    2009-10-01

    Our previous studies showed that administration of a subtoxic dose of acetaminophen (APAP) to female rats increased generation of carbon monoxide from dichloromethane, a metabolic reaction catalyzed mainly by cytochrome P450 (CYP) 2E1. In this study we examined the changes in metabolism and toxicity of APAP upon repeated administration. An intraperitoneal dose of APAP (500 mg/kg) alone did not increase aspartate aminotransferase, alanine aminotransferase, or sorbitol dehydrogenase activity in serum, but was significantly hepatotoxic when the rats had been pretreated with an identical dose of APAP 18 h earlier. The concentrations and disappearance of APAP and its metabolites in plasma were monitored for 8 h after the treatment. APAP pretreatment reduced the elevation of APAP-sulfate, but increased APAP-cysteine concentrations in plasma. APAP or APAP-glucuronide concentrations were not altered. Administration of a single dose of APAP 18 h before sacrifice increased microsomal CYP activities measured with p-nitrophenol, p-nitroanisole, and aminopyrine as probes. Expression of CYP2E1, CYP3A, and CYP1A proteins in the liver was also elevated significantly. The results suggest that administration of APAP at a subtoxic dose may result in an induction of hepatic CYP enzymes, thereby altering metabolism and toxicological consequences of various chemical substances that are substrates for the same enzyme system.

  18. High Efficiency of Human Normal Immunoglobulin for Intravenous Administration in a Patient with Kawasaki Syndrome Diagnosed in the Later Stages

    Directory of Open Access Journals (Sweden)

    T. V. Sleptsova

    2016-01-01

    Full Text Available The article describes a case of late diagnosis of mucocutaneous lymphonodular syndrome (Kawasaki syndrome. At the beginning of the therapy, the child had fever, conjunctivitis, stomatitis, rash, solid swelling of hands and feet, and coronaritis with the development of aneurysms. The article describes the successful use of normal human immunoglobulin for intravenous administration at a dose of 2 g/kg body weight per course in combination with acetylsalicylic acid at the dose of 80 mg/kg per day. After 3 days of treatment, the rash disappeared; limb swelling and symptoms of conjunctivitis significantly reduced; and laboratory parameters of disease activity became normal (erythrocyte sedimentation rate, C-reactive protein concentration. After 3 months, inflammation in the coronary arteries was stopped. After 6 months, a regression of coronary artery aneurysms was recorded. No adverse effects during the immunoglobulin therapy were observed.

  19. An overview of intravenous-related medication administration errors as reported to MEDMARX, a national medication error-reporting program.

    Science.gov (United States)

    Hicks, Rodney W; Becker, Shawn C

    2006-01-01

    Medication errors can be harmful, especially if they involve the intravenous (IV) route of administration. A mixed-methodology study using a 5-year review of 73,769 IV-related medication errors from a national medication error reporting program indicates that between 3% and 5% of these errors were harmful. The leading type of error was omission, and the leading cause of error involved clinician performance deficit. Using content analysis, three themes-product shortage, calculation errors, and tubing interconnectivity-emerge and appear to predispose patients to harm. Nurses often participate in IV therapy, and these findings have implications for practice and patient safety. Voluntary medication error-reporting programs afford an opportunity to improve patient care and to further understanding about the nature of IV-related medication errors.

  20. Latent inhibition is disrupted by acute and repeated administration of corticosterone.

    Science.gov (United States)

    Shalev, U.; Feldon, J.; Weiner, I.

    1998-12-01

    Latent inhibition (LI), namely, a retardation in conditioning to a stimulus, as a consequence of its prior non- reinforced pre-exposure, is disrupted in amphetamine-treated rats and humans and in some subsets of schizophrenic patients. One factor that has been repeatedly implicated in precipitating and/or exacerbating psychotic episodes is stress. Since a principal biological response to stress is the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, leading, as its end product, to the secretion of corticosterone, the present experiments tested whether increase in corticosterone levels following exogenous corticosterone administration would disrupt LI. Both repeated (Experiment 1) and acute (Experiment 2) administration of corticosterone led to LI disruption, providing evidence for the involvement of the HPA axis alterations in LI and further supporting the viability of disrupted LI as an animal model of psychosis. Both regimens also increased amphetamine-induced activity. We suggest that disrupted LI may reflect a cognitive mechanism whereby prolonged periods of increased corticosterone levels can lead to 'sensory flooding' characteristic of psychosis.

  1. Repeated Administration of Bone Marrow-Derived Cells Prevents Disease Progression in Experimental Silicosis

    Directory of Open Access Journals (Sweden)

    Miquéias Lopes-Pacheco

    2013-12-01

    Full Text Available Background/Aims: Bone marrow-derived cells (BMDCs reduced mechanical and histologic changes in the lung in a murine model of silicosis, but these beneficial effects did not persist in the course of lung injury. We hypothesized that repeated administration of BMDCs may decrease lung inflammation and remodeling thus preventing disease progression. Methods: One hundred and two C57BL/6 mice were randomly divided into SIL (silica, 20 mg intratracheally [IT] and control (C groups (saline, IT. C and SIL groups were further randomized to receive BMDCs (2×106 cells or saline IT 15 and 30 days after the start of the protocol. Results: By day 60, BMDCs had decreased the fractional area of granuloma and the number of polymorphonuclear cells, macrophages (total and M1 phenotype, apoptotic cells, the level of transforming growth factor (TGF-β‚ and types I and III collagen fiber content in the granuloma. In the alveolar septa, BMDCs reduced the amount of collagen and elastic fibers, TGF-β, and the number of M1 and apoptotic cells. Furthermore, interleukin (IL-1β, IL-1R1, caspase-3 mRNA levels decreased and the level of IL-1RN mRNA increased. Lung mechanics improved after BMDC therapy. The presence of male donor cells in lung tissue was not observed using detection of Y chromosome DNA. Conclusion: repeated administration of BMDCs reduced inflammation, fibrogenesis, and elastogenesis, thus improving lung mechanics through the release of paracrine factors.

  2. Comparison of behavioral effects after single and repeated administrations of four benzodiazepines in three mice behavioral models.

    Science.gov (United States)

    Bourin, M; Hascoet, M; Mansouri, B; Colombel, M C; Bradwejn, J

    1992-01-01

    The behavioral and clinical profiles of various benzodiazepines after acute and chronic treatment are not well defined and may differ. The aim of this study was to evaluate the behavioral profiles of alprazolam, bromazepam, diazepam and lorazepam in mice after single and repeated (every half-life for seven half-lives) administrations using a stimulation-sedation test (actimeter), a myorelaxation test (rotarod), and an anxiolysis test ("four plates"). A dose range from 0.03 to 4 mg/kg was used. A single administration of alprazolam showed stimulating and anxiolytic effects which diminished after repeated administration. Lorezapam's sedative effect diminished but its anxiolytic effect increased upon repeated administration. Except for lorazepam, the myorelaxing effect of all four drugs increased after repeated treatment. These results suggest that the behavioral profile of benzodiazepines may not be identical during acute and chronic treatment. These differences may be present in clinical treatment and warrant investigation in humans. PMID:1637802

  3. Comparison of behavioral effects after single and repeated administrations of four benzodiazepines in three mice behavioral models.

    Science.gov (United States)

    Bourin, M; Hascoet, M; Mansouri, B; Colombel, M C; Bradwejn, J

    1992-06-01

    The behavioral and clinical profiles of various benzodiazepines after acute and chronic treatment are not well defined and may differ. The aim of this study was to evaluate the behavioral profiles of alprazolam, bromazepam, diazepam and lorazepam in mice after single and repeated (every half-life for seven half-lives) administrations using a stimulation-sedation test (actimeter), a myorelaxation test (rotarod), and an anxiolysis test ("four plates"). A dose range from 0.03 to 4 mg/kg was used. A single administration of alprazolam showed stimulating and anxiolytic effects which diminished after repeated administration. Lorezapam's sedative effect diminished but its anxiolytic effect increased upon repeated administration. Except for lorazepam, the myorelaxing effect of all four drugs increased after repeated treatment. These results suggest that the behavioral profile of benzodiazepines may not be identical during acute and chronic treatment. These differences may be present in clinical treatment and warrant investigation in humans.

  4. Pharmacokinetics of the individual enantiomer S-(+)-ketoprofen after intravenous and oral administration in dogs at two dose levels.

    Science.gov (United States)

    Serrano-Rodríguez, J M; Serrano, J M; Rodríguez, J Morgaz; Machuca, M M Granados; Gómez-Villamandos, R J; Navarrete-Calvo, R

    2014-06-01

    The pharmacokinetic of the individual S-(+)-enantiomer of ketoprofen, S-(+)-ketoprofen, after intravenous (IV) and oral (PO) administration was determined in six dogs at 1 and 3 mg/kg. Plasma concentrations were determined by high performance liquid chromatography with ultraviolet detection. The concentration-time curves were analyzed by non-compartmental methods. Steady-state volume of distribution (Vss) and clearance (Cl) of S-(+)-ketoprofen after IV administration were 0.22 ± 0.07 and 0.19 ± 0.03 L/kg, and 0.10 ± 0.02 and 0.09 ± 0.01 L/h/kg, at 1 and 3 mg/kg, respectively. Following PO administration, S-(+)-ketoprofen achieved maximum plasma concentrations of 4.91 ± 0.76 and 12.47 ± 0.62 μg/ml, at two dose levels, respectively. The absolute bioavailability after PO route was 88.66 ± 12.95% and 85.36 ± 13.90%, respectively.

  5. Use of the novel atypical opioid tapentadol in goats (Capra hircus): pharmacokinetics after intravenous, and intramuscular administration.

    Science.gov (United States)

    Lavy, E; Lee, H-K; Mabjeesh, S J; Sabastian, C; Baker, Y; Giorgi, M

    2014-10-01

    The objective of the present study was to assess the pharmacokinetics of the novel atypical drug tapentadol (TAP) after intravenous (I.V.) and intramuscular (I.M.) injections in clinically healthy goats. A 2 × 2 cross-over design study was carried out. Six local adult Nubian nonlactating, nonpregnant female goats, were given 5 mg/kg body weight of TAP by I.V. and I.M. routes. The concentrations of TAP in plasma were evaluated using a validated HPLC method. Transient adverse effects were noticed in some animals, especially after I.V. administration (tremors and ataxia). Three days after drug administration, severe hair loss was also recorded. The plasma concentrations after the two routes of administration were best described by a bi-compartmental model. After I.M. injection, TAP showed a very fast absorption (Tmax  = 0.17 h) and a short half-life (1.29 h). The I.M. bioavailability was quite high, despite being variable (87.8 ± 35.6%). This is the first pharmacokinetic study of TAP in goats but due to its unknown safety profile and efficacy, it is premature to recommend the use of this drug in clinical ovine practice.

  6. Plasma and ear tissue concentrations of enrofloxacin and its metabolite ciprofloxacin in dogs with chronic end-stage otitis externa after intravenous administration of enrofloxacin.

    Science.gov (United States)

    Cole, Lynette K; Papich, Mark G; Kwochka, Kenneth W; Hillier, Andrew; Smeak, Daniel D; Lehman, Amy M

    2009-02-01

    The purpose of this study was to measure the concentrations of enrofloxacin and its metabolite ciprofloxacin following intravenous administration of enrofloxacin in the plasma and ear tissue of dogs with chronic end-stage otitis undergoing a total ear canal ablation and lateral bulla osteotomy. The goals were to determine the relationship between the dose of enrofloxacin and the concentrations of enrofloxacin and ciprofloxacin, and determine appropriate doses of enrofloxacin for treatment of chronic otitis externa and media. Thirty dogs were randomized to an enrofloxacin-treatment group (5, 10, 15 or 20 mg kg(-1)) or control group (no enrofloxacin). After surgical removal, ear tissue samples (skin, vertical ear canal, horizontal ear canal, middle ear) and a blood sample were collected. Concentrations of enrofloxacin and ciprofloxacin in the plasma and ear tissue were measured by high performance liquid chromatography. Repeated measures models were applied to log-transformed data to assess dosing trends and Pearson correlations were calculated to assess concentration associations. Ear tissue concentrations of enrofloxacin and ciprofloxacin were significantly (P ciprofloxacin concentrations, respectively. For bacteria with an minimal inhibitory concentration of 0.12-0.15 or less, 0.19-0.24, 0.31-0.39 and 0.51-0.64 microg mL(-1), enrofloxacin should be dosed at 5, 10, 15 and 20 mg kg(-1), respectively. Treatment with enrofloxacin would not be recommended for a bacterial organism intermediate or resistant in susceptibility to enrofloxacin since appropriate levels of enrofloxacin would not be attained.

  7. Long-term intravenous administration of carboxylated single-walled carbon nanotubes induces persistent accumulation in the lungs and pulmonary fibrosis via the nuclear factor-kappa B pathway

    Directory of Open Access Journals (Sweden)

    Qin Y

    2016-12-01

    Full Text Available Yue Qin,1,* Suning Li,2,* Gan Zhao,2,* Xuanhao Fu,1 Xueping Xie,1 Yiyi Huang,1 Xiaojing Cheng,3 Jinbin Wei,1 Huagang Liu,1 Zefeng Lai1 1Pharmaceutical College, Guangxi Medical University, 2Department of Pharmacy, The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, 3Life Sciences Institute, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China *These authors contributed equally to this work Abstract: Numerous studies have demonstrated promising application of single-walled carbon nanotubes (SWNTs in drug delivery, diagnosis, and targeted therapy. However, the adverse health effects resulting from intravenous injection of SWNTs are not completely understood. Studies have shown that levels of “pristine” or carboxylated carbon nanotubes are very high in mouse lungs after intravenous injection. We hypothesized that long-term and repeated intravenous administration of carboxylated SWNTs (c-SWNTs can result in persistent accumulation and induce histopathologic changes in rat lungs. Here, c-SWNTs were administered repeatedly to rats via tail-vein injection for 90 days. Long-term intravenous injection of c-SWNTs caused sustained embolization in lung capillaries and granuloma formation. It also induced a persistent inflammatory response that was regulated by the nuclear factor-kappa B signaling pathway, and which resulted in pulmonary fibrogenesis. c-SWNTs trapped within lung capillaries traversed capillary walls and injured alveolar epithelial cells, thereby stimulating production of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta and pro-fibrotic growth factors (transforming growth factor-beta 1. Protein levels of type-I and type-III collagens, matrix metalloproteinase-2, and the tissue inhibitor of metalloproteinase-2 were upregulated after intravenous exposure to c-SWNTs as determined by immunohistochemical assays and Western blotting, which suggested collagen deposition

  8. Systemic and direct nose-to-brain transport pharmacokinetic model for remoxipride after intravenous and intranasal administration.

    Science.gov (United States)

    Stevens, Jasper; Ploeger, Bart A; van der Graaf, Piet H; Danhof, Meindert; de Lange, Elizabeth C M

    2011-12-01

    Intranasal (IN) administration could be an attractive mode of delivery for drugs targeting the central nervous system, potentially providing a high bioavailability because of avoidance of a hepatic first-pass effect and rapid onset of action. However, controversy remains whether a direct transport route from the nasal cavity into the brain exists. Pharmacokinetic modeling is proposed to identify the existence of direct nose-to-brain transport in a quantitative manner. The selective dopamine-D2 receptor antagonist remoxipride was administered at different dosages, in freely moving rats, by the IN and intravenous (IV) route. Plasma and brain extracellular fluid (ECF) concentration-time profiles were obtained and simultaneously analyzed using nonlinear mixed-effects modeling. Brain ECF/plasma area under the curve ratios were 0.28 and 0.19 after IN and IV administration, respectively. A multicompartment pharmacokinetic model with two absorption compartments (nose-to-systemic and nose-to-brain) was found to best describe the observed pharmacokinetic data. Absorption was described in terms of bioavailability and rate. Total bioavailability after IN administration was 89%, of which 75% was attributed to direct nose-to brain transport. Direct nose-to-brain absorption rate was slow, explaining prolonged brain ECF exposure after IN compared with IV administration. These studies explicitly provide separation and quantitation of systemic and direct nose-to-brain transport after IN administration of remoxipride in the rat. Describing remoxipride pharmacokinetics at the target site (brain ECF) in a semiphysiology-based manner would allow for better prediction of pharmacodynamic effects.

  9. Pharmacokinetics of marbofloxacin in mature horses after single intravenous and intramuscular administration.

    Science.gov (United States)

    Carretero, M; Rodríguez, C; San Andrés, M I; Forés, P; de Lucas, J J; Nieto, J; Waxman, S; San Andrés, M D; González, F

    2002-07-01

    The pharmacokinetic behaviour of marbofloxacin, a new fluoroquinolone antimicrobial agent developed exclusively for veterinary use, was studied in mature horses (n = 5) after single-dose i.v. and i.m. administrations of 2 mg/kg bwt. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) and data obtained were subjected to compartmental and noncompartmental kinetic analysis. This compound presents a relatively high volume of distribution (V(SS) = 1.17 +/- 0.18 l/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.19 +/- 0.042 l/kgh, which is related to a long elimination half-life (t(1/2beta) = 4.74 +/- 0.8 h and 5.47 +/- 1.33 h i.v. and i.m. respectively). Marbofloxacin was rapidly absorbed after i.m. administration (MAT = 33.8 +/- 14.2 min) and presented high bioavailability (F = 87.9 +/- 6.0%). Pharmacokinetic parameters are not significantly different between both routes of administration (P>0.05). After marbofloxacin i.m. administration, no adverse reactions at the site of injection were observed. Serum CK activity levels 12 h after administration increased over 8-fold (range 3-15) compared with pre-injection levels, but this activity decreased to 3-fold during the 24 h follow-up period. Based on the value of surrogate markers to predict clinical success, Cmax/MIC ratio or AUC/MIC ratio, single daily marbofloxacin dose of 2 mg/kg bwt may not be effective in treating infections in horses caused by pathogens with an MIC > or = 0.25 microg/ml. However, if we use a classical antimicrobial efficacy criteria, marbofloxacin can reach a high plasma peak concentration and maintain concentrations higher than MICs determined for marbofloxacin against most gram-negative veterinary pathogens throughout the administration period. Taking into account the fact that fluoroquinolones are considered to have a concentration-dependent effect and a long postantibiotic effect against gram-negative bacteria, a dose

  10. Metabolism and disposition of [(14)C]dimethylamine borane in male Harlan Sprague Dawley rats following gavage administration, intravenous administration and dermal application.

    Science.gov (United States)

    Mathews, James M; Watson, Scott L; Patel, Purvi R; Black, Sherry R; Hong, Yan; Levine, Keith E; Ross, Glenn; Germolec, Dori R; Thakur, Sheetal A; Waidyanatha, Suramya

    2014-01-01

    1. Dimethylamine borane (DMAB) is used as a reducing agent in the manufacturing of a variety of products and in chemical synthesis. National Toxicology Program is evaluating the toxicity of DMAB in rodents following dermal application. The objective of this study was to evaluate the metabolism and disposition of DMAB in male Harlan Sprague Dawley (HSD) rats. 2. Disposition of radioactivity was similar between gavage and intravenous administration of 1.5 mg/kg [(14)C] DMAB, with nearly 84%-89% of the administered radioactivity recovered in urine 24 h post dosing. At 72 h, only 1% or less was recovered in feces, 0.3% as CO2, and 0.5%-1.4% as volatiles and 0.3%-0.4 % in tissues. 3. The absorption of [(14)C]DMAB following dermal application was moderate; percent dose absorbed increased with the dose, with 23%, 32% and 46% of dose absorbed at 0.15, 1.5 and 15 mg/kg, respectively. Urinary and fecal excretion ranged from 18%-37% and 2%-4% of dose, respectively, and 0.1%-0.2% as CO2, and 1%-3% as volatiles. Tissue retention of the radiolabel was low ∼1%, but was higher than following the gavage or intravenous administration. 4. Following co-adminsitration of DMAB and sodium nitrite by gavage, N-nitrosodimethylamine was not detected in blood or urine above the limit of quantitation of the analytical method of 10 ng/mL. 5. Absorption of DMAB in fresh human skin in vitro was ∼41% of the applied dose: the analysis of the receptor fluid shows that the intact DMAB complex can be absorbed through the skin.

  11. [Hyperkalemia caused by intravenous administration of mannitol in a patient with arteriovenous malformation: case report].

    Science.gov (United States)

    Kimura, Shigeyoshi; Ogawa, Haruhiko; Katayama, Yoichi

    2006-01-01

    We experienced a case in which hyperkalemia was induced by mannitol administration. The medication with mannitol was given to a 15-year-old male patient who underwent a removal operation for arteriovenous malformation under general anesthesia. Following the mannitol infusion, his arterial blood gas and electrolyte analysis revealed severe metabolic acidosis and an increase in serum potassium. Furthermore, a change in his electrocardiogram was observed. The hyperkalemia was quickly normalized by medication with calcium gluconate and sodium bicarbonate. We stopped the removal operation with the aim of giving priority to the patient's safety. It is speculated that the hyperkalemia was caused by the administration of mannitol. Checks of electrolyte levels, arterial blood gas analysis and electrocardiogram monitoring should therefore be carried out when using mannitol, especially in an emergency situation such as intracranial hemorrhage.

  12. Preference for subcutaneous or intravenous administration of trastuzumab in patients with HER2-positive early breast cancer (PrefHer)

    DEFF Research Database (Denmark)

    Pivot, Xavier; Gligorov, Joseph; Müller, Volkmar;

    2013-01-01

    Subcutaneous trastuzumab has shown non-inferior efficacy and a similar pharmacokinetic and safety profile when compared with intravenous trastuzumab in patients with HER2-positive early breast cancer. We assessed patient preference for either subcutaneous or intravenous trastuzumab...

  13. The impact of intravenous fat emulsion administration in acute lung injury.

    Science.gov (United States)

    Lekka, Marilena E; Liokatis, Stamatis; Nathanail, Christos; Galani, Vasiliki; Nakos, George

    2004-03-01

    The aim of this study was to evaluate the effect of parenteral nutrition containing medium- and long-chain triglycerides on the function of the respiratory system and to investigate mechanisms involved in this process. We studied 13 patients with acute respiratory distress syndrome (ARDS), 8 receiving lipid and 5 placebo, and 6 without ARDS, receiving lipid. Bronchoalveolar lavage (BAL) was performed before and 1 hour after administration of lipid or placebo. In patients with ARDS, lipid administration resulted in deterioration of oxygenation (Pa(O(2))/FI(O(2)): from 129 +/- 37 to 95 +/- 42), compliance of respiratory system (from 39.2 +/- 12 to 33.1 +/- 9.2 ml/cm H(2)O), and pulmonary vascular resistance (from 258 +/- 47 to 321 +/- 58 dyne x s x cm(-5)). In the BAL fluid of the same group, an increase in total protein and phospholipid concentrations, phospholipase activities, platelet-activating factor and neutrophils, as well as alterations in BAL lipid profile were observed. No significant changes were observed in the control or in the ARDS-Placebo groups. In conclusion, this study indicates that administration of medium- and long-chain triglycerides in patients with ARDS causes alterations in lung function and hemodynamics. Inflammatory cells, possibly activated by lipids, release phospholipase A(2) and platelet-activating factor, enhancing edema formation, inflammation, and surfactant alterations.

  14. Intravenous tryptophan administration attenuates cortisol secretion induced by intracerebroventricular injection of noradrenaline.

    Science.gov (United States)

    Sutoh, Madoka; Kasuya, Etsuko; Yayou, Ken-ichi; Ohtani, Fumihiro; Kobayashi, Yosuke

    2016-02-01

    This study was conducted to investigate the possibility of suppression of stress-induced cortisol (CORT) secretion by tryptophan (TRP) administration and to better understand its regulatory mechanisms by using a noradrenaline (NA) injection into the third ventricle (3V) as a stress model in cattle. A total of 25 Holstein steers with a cannula in the 3V were used. First, the increase in CORT secretion was observed following a NA injection into the 3V in a dose-dependent manner, verifying the appropriateness of this treatment as a stress model of CORT secretion (Experiment 1). The effect of prior-administration of TRP into peripheral blood with a dose that has been demonstrated to increase brain 5-hydroxytryptamine levels on the elevation of plasma CORT induced by NA or corticotropin-releasing hormone (CRH) was then examined (Experiment 2). The prior administration of TRP suppressed NA-induced, but not CRH-induced, CORT elevation. These results suggest that an increase in TRP absorption into peripheral blood could suppress the stress-induced CORT secretion in cattle via the attenuation of the stimulatory effect of NA on the hypothalamic CRH release.

  15. Pharmacokinetics after intravenous administration of flunixin meglumine in budgerigars (Melopsittacus undulatus) and Patagonian conures (Cyanoliseus patagonus).

    Science.gov (United States)

    Musser, Jeffrey M B; Heatley, J Jill; Phalen, David N

    2013-01-15

    To investigate the disposition kinetics of flunixin meglumine when administered IV to budgerigars (Melopsittacus undulatus) and Patagonian conures (Cyanoliseus patagonus). Prospective cohort study. 8 adult Patagonian conures and 24 adult budgerigars. Injectable flunixin meglumine (50 mg/mL) was diluted to 10 and 1. 0 mg/mL and administered IV at a dose of 5.0 mg/kg (2.3 mg/lb) to Patagonian conures and budgerigars, respectively. In budgerigars, the elimination half-life was 0.72 hours and the mean residence time was 0.73 hours. In Patagonian conures, the elimination half-life was 0.91 hours and the mean residence time was 1.20 hours. The concentration of flunixin was below the assay's limit of quantification (0.5 μg/mL) at 3 and 6 hours in budgerigars and Patagonian conures, respectively. A single budgerigar developed adverse effects (lethargy and signs of depression) for approximately 15 minutes following drug administration. The half-life of flunixin in Patagonian conures and budgerigars was short following IV administration; however, results of this study suggested that IV administration of injectable flunixin meglumine at 5.0 mg/kg resulted in plasma concentrations that could potentially be anti-inflammatory and analgesic in budgerigars and Patagonian conures.

  16. Pharmacokinetics and distribution of Huwen toxin—1 after epidural and intravenous administration to rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    LiuXW; LiaoZ

    2002-01-01

    Huwen toxin-1(HWTX-1) was adminstered at a dose of 0.388 MBq·kg-1 by lumbar puncture at the third and the fourth lumbar interspace or ivat the same dose.Comcentrations were determined by reverse phase-high performance liquid chromatography.Tissue distribution was detected by γ-counter.Radioactivity detected in epidural space was 38% of injected radioactivity at 10min after injection.The maximum plasma concentration after epidural or iv administration were(0.70±0.04) and (5.0±0.6)MBq·L-1,respectively.The maximum plasma concentration intimes were 30 and 2 min,respectively.Teminal T1/2 were(10.36±0.27) and (11.03±1.16)h,respectively.Cls were(1.29±0.07) and (1.25±0.23)L·h-1·kg-1,respectively,Bioavailabilit after epidural administration was>90%.Distributions of [125I] HWTX-1 between two routes were different,and the exposed levels in most tissues at 10min after iv were higher than those after epidural administration(P>0.05).

  17. Pharmacokinetics and tissue disposition of meloxicam in beef calves after repeated oral administration.

    Science.gov (United States)

    Coetzee, J F; Mosher, R A; Griffith, G R; Gehring, R; Anderson, D E; KuKanich, B; Miesner, M

    2015-12-01

    The objective of this study was to investigate the pharmacokinetics and tissue disposition of meloxicam after repeated oral administration in calves. Thirteen male British × Continental beef calves aged 4 to 6 months and weighing 297-392 kg received 0.5 mg/kg meloxicam per os once daily for 4 days. Plasma meloxicam concentrations were determined in 8 calves over 6 days after first treatment. Calves were randomly assigned to be euthanized at 5, 10, 15 (n = 3/timepoint), and 19 days (n = 4) after final administration. Meloxicam concentrations were determined in plasma (LOQ= 0.025 μg/mL) and muscle, liver, kidney, and fat samples (LOQ = 2 ng/g) after extraction using validated LC-MS-MS methods. The mean (± SD) Cmax , Cmin , and Caverage plasma meloxicam concentrations were 4.52 ± 0.87 μg/mL, 2.95 ± 0.77 μg/mL, and 3.84 ± 0.81 μg/mL, respectively. Mean (± SD) tissue meloxicam concentrations were highest in liver (226.67 ± 118.16 ng/g) and kidney samples (52.73 ± 39.01 ng/g) at 5 days after final treatment. Meloxicam concentrations were below the LOQ in all tissues at 15 days after treatment. These findings suggest that tissue from meloxicam-treated calves will have low residue concentrations by 21 days after repeated oral administration.

  18. Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke.

    Science.gov (United States)

    Honmou, Osamu; Houkin, Kiyohiro; Matsunaga, Takuya; Niitsu, Yoshiro; Ishiai, Sumio; Onodera, Rie; Waxman, Stephen G; Kocsis, Jeffery D

    2011-06-01

    Transplantation of human mesenchymal stem cells has been shown to reduce infarct size and improve functional outcome in animal models of stroke. Here, we report a study designed to assess feasibility and safety of transplantation of autologous human mesenchymal stem cells expanded in autologous human serum in stroke patients. We report an unblinded study on 12 patients with ischaemic grey matter, white matter and mixed lesions, in contrast to a prior study on autologous mesenchymal stem cells expanded in foetal calf serum that focused on grey matter lesions. Cells cultured in human serum expanded more rapidly than in foetal calf serum, reducing cell preparation time and risk of transmissible disorders such as bovine spongiform encephalomyelitis. Autologous mesenchymal stem cells were delivered intravenously 36-133 days post-stroke. All patients had magnetic resonance angiography to identify vascular lesions, and magnetic resonance imaging prior to cell infusion and at intervals up to 1 year after. Magnetic resonance perfusion-imaging and 3D-tractography were carried out in some patients. Neurological status was scored using the National Institutes of Health Stroke Scale and modified Rankin scores. We did not observe any central nervous system tumours, abnormal cell growths or neurological deterioration, and there was no evidence for venous thromboembolism, systemic malignancy or systemic infection in any of the patients following stem cell infusion. The median daily rate of National Institutes of Health Stroke Scale change was 0.36 during the first week post-infusion, compared with a median daily rate of change of 0.04 from the first day of testing to immediately before infusion. Daily rates of change in National Institutes of Health Stroke Scale scores during longer post-infusion intervals that more closely matched the interval between initial scoring and cell infusion also showed an increase following cell infusion. Mean lesion volume as assessed by magnetic

  19. Associations of OPRM1 A118G and alcohol sensitivity with intravenous alcohol self-administration in young adults.

    Science.gov (United States)

    Hendershot, Christian S; Claus, Eric D; Ramchandani, Vijay A

    2016-01-01

    Human laboratory and animal models implicate variation in the μ-opioid receptor gene (OPRM1) as relevant for alcohol-related reward. OPRM1 is associated with alcohol self-administration in non-human primate studies, but the relevance of this finding to human models is unclear. This study used computer-assisted self-infusion of ethanol (CASE) to examine associations among OPRM1 A118G genotype, subjective responses to alcohol and intravenous alcohol self-administration in young heavy drinkers (n = 40, mean age = 19.95 years, SD = 0.82). Participants completed a 2-hour CASE session comprising a priming phase followed by ad libitum self-administration in a free-access paradigm. Participants achieved a mean peak breath alcohol concentration (BrAC) of 81.18 mg% (SD = 24.96). Those with the OPRM1 118G variant (GA or GG genotypes) achieved significantly higher peak BrAC (M = 94.90 mg%, SD = 16.56) than those with the AA genotype (M = 74.46 mg%, SD = 25.36), reflecting a significantly greater number of alcohol requests among GA/GG participants. Eighty percent of GA/GG participants surpassed a threshold defining a laboratory analog of heavy alcohol exposure (80 mg%) compared with 46 percent of AA participants. Results indicated significant associations between subjective measures of alcohol sensitivity and CASE outcomes, although the pattern of findings differed across self-report measures. Subjective responses did not differ by OPRM1 status. These results offer further support for the feasibility of the CASE paradigm and provide initial evidence for an association of OPRM1 with alcohol self-administration in a human laboratory context. © 2014 Society for the Study of Addiction.

  20. A pilot study assessing the bioavailability and pharmacokinetics of diazepam after intranasal and intravenous administration in healthy volunteers.

    Science.gov (United States)

    Agarwal, Suresh K; Kriel, Robert L; Brundage, Richard C; Ivaturi, Vijay D; Cloyd, James C

    2013-08-01

    Diazepam rectal gel (Diastat(®)) is the only FDA-approved product indicated for acute repetitive seizures. Despite its proven efficacy, most older children and adults object to this route of administration. As a result, many patients do not realize the benefit of a therapy that can improve outcomes and decrease healthcare costs. Intranasal administration of benzodiazepines offers a potential alternative. The primary objective of this study was to compare the bioavailability and pharmacokinetics of two novel intranasal (IN) diazepam (DZP) formulations versus intravenous (IV) administration in healthy volunteers. Twenty-four healthy volunteers were randomized into an open-label, three-way crossover study. 10mg doses of two investigational intranasal DZP formulations (solution, suspension) and a 5mg IV dose of commercially available DZP injectable, USP were given. A two-week washout period separated treatments. Plasma samples for DZP analysis were collected pre-dose and at regular intervals up to 240 h post-dose. DZP concentration-time data were analyzed using a non-compartmental pharmacokinetics approach. Exposure following administration of DZP IN solution (absolute bioavailability - 97%) was greater than the IN suspension (absolute bioavailability - 67%). Mean Cmaxvalues for the suspension and solution formulations were 221 ng/mL and 272 ng/mL, respectively. Median time to maximum concentration (Tmax) was 1h and 1.5h for suspension and solution formulation, respectively. Both investigational intranasal formulations were well tolerated. The results of this pilot study indicate that development of an intranasal diazepam formulation with high bioavailability, reasonable variability, and good tolerability is feasible.

  1. Complement activation-related pseudoallergy in dogs following intravenous administration of a liposomal formulation of meglumine antimoniate

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    Raul R. Ribeiro

    2013-08-01

    Full Text Available The increasing use of nanotechnologies in advanced therapies has allowed the observation of specific adverse reactions related to nanostructures. The toxicity of a novel liposome formulation of meglumine antimoniate in dogs with visceral leishmaniasis after single dose has been investigated. Groups of 12 animals received by the intravenous route a single dose of liposomal meglumine antimoniate (group I [GI], 6.5 mg Sb/kg, empty liposomes (GII or isotonic saline (GIII. Evaluation of hematological and biochemical parameters showed no significant changes 4 days after administration. No undesired effects were registered in the GIII. However, adverse reactions were observed in 67.7% of dogs from both groups that received liposomal formulations. The side effects began moments after bolus administration and disappeared during the first 15 minutes after treatment. Prostation, sialorrhea and defecation were the most frequent clinical signs, registered in 33.3% and 41.6 % of animals from the groups GI and GII, respectively. Tachypnea, mydriasis, miosis, vomiting and cyanosis were also registered in both groups. The adverse reactions observed in this study were attributed to the activation of the complement system by lipid vesicles in a phenomenon known as Complement Activation-Related Pseudoallergy (CARPA. The influence of the physical-chemical characteristics of liposomal formulation in the triggering of CARPA is discussed.

  2. Toxicity of zinc oxide nanoparticles in rats treated by two different routes: single intravenous injection and single oral administration.

    Science.gov (United States)

    Choi, Jonghye; Kim, Heyjin; Kim, Pilje; Jo, Eunhye; Kim, Hyun-Mi; Lee, Moo-Yeol; Jin, Seon Mi; Park, Kwangsik

    2015-01-01

    Toxicokinetics of zinc oxide nanoparticles (ZnONP) was studied in rats via a single intravenous (iv) injection and a single oral administration (3 mg/kg or 30 mg/kg), respectively. Blood concentrations of zinc (Zn) were monitored for 7 d and tissue distribution were determined in liver, kidneys, lung, spleen, thymus, brain, and testes. To ascertain the excretion of ZnONP, Zn levels in urine and feces were measured for 7 d. ZnONP were not readily absorbed from the gastrointestinal tract (GIT) after oral administration and were excreted mostly in feces. When the nanoparticles were injected iv to rats at a dose of 30 mg/kg, peak concentration appeared at 5 min but returned to normal range by d 2 (48 h after injection). ZnONP were distributed mainly to liver, kidneys, lung, and spleen, but not to thymus, brain, and testes. The distribution level was significantly decreased to normal by d 7. Feces excretion levels after iv injection supported biliary excretion of ZnONP. In rats injected iv with 30 mg/kg, mitotic figures in hepatocytes were significantly increased and multifocal acute injuries with dark brown pigment were noted in lungs, while no significant damage was observed in rats treated orally with the same dosage.

  3. Effects of oral and intravenous administration of buspirone on food-cocaine choice in socially housed male cynomolgus monkeys.

    Science.gov (United States)

    Czoty, Paul W; Nader, Michael A

    2015-03-13

    Drugs acting at D3 dopamine receptors have been suggested as medications for cocaine dependence. These experiments examined the effects of intravenously and orally administered buspirone, a D2-like receptor antagonist with high affinity for D3 and D4 receptors, on the relative reinforcing strength of cocaine in group-housed male cynomolgus monkeys. Use of socially housed monkeys permitted the assessment of whether social status, known to influence D2-like receptor availability, modulates the behavioral effects of buspirone. Buspirone was administered acutely to monkeys self-administering cocaine under a food-drug choice procedure in which a cocaine self-administration dose-effect curve was determined daily. When administered by either route, buspirone significantly decreased cocaine choice in dominant-ranked monkeys. In subordinate monkeys, however, i.v. buspirone was ineffective on average, and oral buspirone increased choice of lower cocaine doses. The effects of buspirone only differed according to route of administration in subordinate monkeys. Moreover, it is noteworthy that the effects of buspirone were similar to those of the D3 receptor-selective antagonist PG01037 and qualitatively different than those of less selective drugs that act at D2-like or serotonin (5-HT)1A receptors, suggesting a D3 and possibly D4 receptor mechanism of action for buspirone. Taken together, the data support the utility of drugs targeting D3/D4 receptors as potential treatments for cocaine addiction, particularly in combination with enriching environmental manipulations.

  4. Systemic and immunotoxicity of pristine and PEGylated multi-walled carbon nanotubes in an intravenous 28 days repeated dose toxicity study

    Science.gov (United States)

    Zhang, Ting; Tang, Meng; Zhang, Shanshan; Hu, Yuanyuan; Li, Han; Zhang, Tao; Xue, Yuying; Pu, Yuepu

    2017-01-01

    The numerous increasing use of carbon nanotubes (CNTs) derived from nanotechnology has raised concerns about their biosafety and potential toxicity. CNTs cause immunologic dysfunction and limit the application of CNTs in biomedicine. The immunological responses induced by pristine multi-walled carbon nanotubes (p-MWCNTs) and PEGylated multi-walled carbon nanotubes (MWCNTs-PEG) on BALB/c mice via an intravenous administration were investigated. The results reflect that the p-MWCNTs induced significant increases in spleen, thymus, and lung weight. Mice treated with p-MWCNTs showed altered lymphocyte populations (CD3+, CD4+, CD8+, and CD19+) in peripheral blood and increased serum IgM and IgG levels, and splenic macrophage ultrastructure indicated mitochondria swelling. p-MWCNTs inhibited humoral and cellular immunity function and were associated with decreased immune responses against sheep erythrocytes and serum hemolysis level. Natural killer (NK) activity was not modified by two types of MWCNTs. In comparison with two types of MWCNTs, for a same dose, p-MWCNTs caused higher levels of inflammation and immunosuppression than MWCNTs-PEG. The results of immunological function suggested that after intravenous administration with p-MWCNTs caused more damage to systemic immunity than MWCNTs-PEG. Here, we demonstrated that a surface functional modification on MWCNTs reduces their immune perturbations in vivo. The chemistry-modified MWCNTs change their preferred immune response in vivo and reduce the immunotoxicity of p-MWCNTs. PMID:28280324

  5. Evaluation of safety profile of black shilajit after 91 days repeated administration in rats

    Institute of Scientific and Technical Information of China (English)

    Velmurugan C; Vivek B; Wilson E; Bharathi T; Sundaram T

    2012-01-01

    Objective: To evaluate the safety of shilajit by 91 days repeated administration in different dose levels in rats. Methods: In this study the albino rats were divided into four groups. Group I received vehicle and group II, III and IV received 500, 2500 and 5000 mg/kg of shilajit, respectively. Finally animals were sacrificed and subjected to histopathology and iron was estimated by flame atomic absorption spectroscopy and graphite furnace. Results: The result showed that there were no significant changes in iron level of treated groups when compared with control except liver (5000 mg/kg) and histological slides of all organs revealed normal except negligible changes in liver and intestine with the highest dose of shilajit. The weight of all organs was normal when compared with control. Conclusions: The result suggests that black shilajit, an Ayurvedic formulation, is safe for long term use as a dietary supplement for a number of disorders like iron deficiency anaemia.

  6. A Study of Intravenous Administration of Vitamin C in the Treatment of Acute Herpetic Pain and Postherpetic Neuralgia

    Science.gov (United States)

    Kim, Min Sung; Kim, Dong Jin; Na, Chan Ho

    2016-01-01

    Background Although there are several available management strategies for treatment of both acute pain of herpes zoster (HZ) and postherpetic neuralgia (PHN), it is difficult to treat them adequately. Objective The aim of this study was to evaluate the efficacy of intravenously administrated vitamin C on acute pain and its preventive effects on PHN in patients with HZ. Methods Between September 2011 and May 2013 eighty-seven patients who were admitted for HZ were assessed according to age, sex, underlying diseases, duration of pain and skin lesion, dermatomal distribution, and PHN. It was a randomized controlled study, in which 87 patients were randomly allocated into the ascorbic acid group and control group. Each patient received normal saline infusion with or without 5 g of ascorbic acid on days 1, 3, and 5 then answered questionnaires that included side effects and pain severity using visual analogue scale on days 1, 2, 3, 4, and 5. After discharge, the severity of pain was obtained at out-patient clinic or by telephone on weeks 2, 4, 8, and 16. Results There was no differences in severity of pain on patients' age, sex, underlying diseases, duration of pain and skin lesion and dermatomal distribution between two groups (p>0.05). Since 8th week, pain score in ascorbic acid treatment group was significantly lower than control group (p <0.05). The incidence of PHN was significantly lower in the treatment group compared to control group (p=0.014). The changes of overall pain score was significantly different between the two groups (p<0.05). Conclusion Intravenously administered ascorbic acid did not relieve acute HZ pain; but is effective for reducing the incidence of PHN. PMID:27904265

  7. Pharmacokinetics of dl-praeruptorin A after single-dose intravenous administration to rats with liver cirrhosis

    Directory of Open Access Journals (Sweden)

    X Zhu

    2011-07-01

    Full Text Available "n  Background and the purpose of the study: As a novel drug in the treatment of cardiac diseases, dl-praeruptorin A (Pd-Ia is the major active component of traditional herbal medicine Peucedanum praeruptorum Dunn and is metabolized primarily via cytochrome P450 isozymes (CYP 3A1 and 3A2 in rats. In the present study, the influence of liver cirrhosis on pharmacokinetics of Pd-Ia and hepatic mRNA expression of CYP3A1 and 3A2 in rats with experimental liver cirrhosis (LC rats were evaluated. "n  Methods: Pd-Ia was given intravenously (5 mg·kg-1 to LC rats induced by dimethylnitrosamine and pharmacokinetic variables were measured. Enzyme kinetic metabolism of Pd-Ia in rat hepatic microsomes was also investigated and hepatic mRNA expression of CYP3A1 and 3A2 were measured by real-time PCR. "n  Results and major conclusion: After intravenous administration in LC rats, the area under the plasma concentration-time curve from time zero to infinity (AUC0-∞ was significantly greater than that in control rats, which might be due to slower rate of the hepatic blood flow and significant slower hepatic intrinsic clearance (CLint in rats. The decreased metabolic clearance of Pd-Ia in LC rats might be at least partly caused by the decreased levels of CYP3A1 and 3A2 responsible for Pd-Ia metabolism. These findings may provide new insights into the inter- and intra-individual pharmacokinetic variability of Pd-Ia.

  8. Anxiolytic profile of fluoxetine as monitored following repeated administration in animal rat model of chronic mild stress

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    Muhammad Farhan

    2016-09-01

    Full Text Available Background: Fluoxetine, a selective serotonin re-uptake inhibitor (SSRI, has been proposed to be more effective as an antidepressive drug as compared to other SSRIs. After chronic SSRI administration, the increase in synaptic levels of 5-HT leads to desensitization of somatodentritic 5-HT autoreceptors in the raphe nuclei. Chronic stress may alter behavioral, neurochemical and physiological responses to drug challenges and novel stressors. Methods: Twenty four male rats were used in this study. Animals of CMS group were exposed to CMS. Animals of stressed and unstressed group were administrated with fluoxetine at dose of 1.0 mg/kg s well as 5.0 mg/kg repeatedly for 07 days 1 h before exposed to CMS. The objective of the present study was to evaluate that repeated treatment with fluoxetine could attenuate CMS-induced behavioral deficits. Results: Treatment with fluoxetine attenuated CMS-induced behavioral deficits. Fluoxetine administration induced hypophagia in unstressed as well as CMS rats. Acute and repeated administration of fluoxetine increased motor activity in familiar environment but only repeated administration increased exploratory activity in open field. Anxiolytic effects of fluoxetine were greater in unstressed rats. These anxiolytic effects were produced as result of repeated administration not on acute administration of fluoxetine at 1.0 mg/kg as well as 5.0 mg/kg. Conclusion: The present study demonstrated that CMS exposure resulted into behavioral deficits and produced depressive-like symptoms. Fluoxetine, an SSRI, administration attenuated behavioral deficits induced by CMS. Anxiolytic effects of repeated fluoxetine administration were greater in unstressed than CMS animals.

  9. Repeated administration of dopaminergic agents in the dorsal hippocampus and morphine-induced place preference.

    Science.gov (United States)

    Zarrindast, M-R; Nasehi, M; Rostami, P; Rezayof, A; Fazli-Tabaei, S

    2005-03-01

    The aim of the present experiments was to investigate whether repeated intra-hippocampal CA1 (intra-CA1) administration of dopaminergic agents can affect morphine-induced conditioned place preference (CPP). Effects of repeated intra-CA1 injections of dopamine (DA) receptor agonists and antagonists on morphine-induced CPP in rats were investigated using an unbiased 3-day schedule of place conditioning. Animals receiving once-daily subcutaneous (s.c.) injections of morphine (1-9 mg/kg) or saline (1.0 ml/kg, s.c.) showed a significant place preference in a dose-dependent manner: the maximum response was observed with 3 mg/kg morphine. Three days' intra-CA1 injections of apomorphine (0.25-1 microg/rat) followed by 5 days free of the drug, significantly decreased morphine CPP (1 and 3 mg/kg, s.c.). Moreover, pre-treatment with the highest dose of apomorphine (1 microg/rat) altered the effect of morphine to an aversive response. The morphine (1 and 3 mg/kg) CPP was also significantly decreased in animals that previously received three intra-CA1 injections of SKF 38393 (2-9 microg/rat), quinpirole (1-3 microg/rat) or sulpiride (1-3 microg/rat), and significantly increased in animals that had previously received three intra-CA1 injections of SCH 23390 (0.02 microg/rat). The 3-day pre-treatment with apomorphine, SKF 38393 or quinpirole reduced locomotor activity in the test session, while SCH 23390 and sulpiride did not have any influence on locomotor activity. It is concluded that repeated injections of DA receptor agents in the dorsal hippocampus, followed by 5 days free of the drugs, can affect morphine reward.

  10. Pharmacokinetics and metabolism of cyadox and its main metabolites in beagle dogs following oral, intramuscular and intravenous administration

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    Adeel Sattar

    2016-08-01

    Full Text Available Cyadox (Cyx is an antibacterial drug of the quinoxaline group that exerts markedly lower toxicity in animals, compared to its congeners. Here, the pharmacokinetics and metabolism of Cyx after oral (PO, intramuscular (IM and intravenous (IV routes of administration were studied to establish safety criteria for the clinical use of Cyx in animals. Six beagle dogs (3 males, 3 females were administered Cyx through PO (40 mg kg-1 b.w., IM (10 mg kg-1 b.w. and IV (10 mg kg-1 b.w. routes with a washout period of 2 weeks in a crossover design. Highly sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV was employed for determination of Cyx and its main metabolites, 1, 4-bisdesoxycyadox (Cy1, cyadox-1-monoxide (Cy2, N-(quinoxaline-2-methyl-cyanide acetyl hydrazine (Cy4 and quinoxaline-2-carboxylic acid (Cy6 in plasma, urine and feces of dogs. The oral bioavailability of Cyx was 4.75%, suggesting first-pass effect in dogs. The concentration vs. time profile in plasma after PO administration indicates that Cyx is rapidly dissociated into its metabolites and eliminated from plasma earlier, compared to its metabolites. The areas under the curve (AUC of Cyx after PO, IM and IV administration were 1.22 h×µg mL-1, 6.3 h×µg mL-1, and 6.66 h×µg mL-1, while mean resident times (MRT were 7.32, 3.58 and 0.556 h, respectively. Total recovery of Cyx and its metabolites was >60% with each administration route. In feces, 48.83% drug was recovered after PO administration, while 18.15% and 17.11% after IM and IV injections, respectively, suggesting renal clearance as the major route of excretion with IM and IV administration and feces as the major route with PO delivery. Our comprehensive evaluation of Cyx has uncovered detailed information that should facilitate its judicious use in animals by improving understanding of its pharmacology.

  11. Pharmacokinetics and Metabolism of Cyadox and Its Main Metabolites in Beagle Dogs Following Oral, Intramuscular, and Intravenous Administration.

    Science.gov (United States)

    Sattar, Adeel; Xie, Shuyu; Huang, Lingli; Iqbal, Zahid; Qu, Wei; Shabbir, Muhammad A; Pan, Yuanhu; Hussain, Hafiz I; Chen, Dongmei; Tao, Yanfei; Liu, Zhenli; Iqbal, Mujahid; Yuan, Zonghui

    2016-01-01

    Cyadox (Cyx) is an antibacterial drug of the quinoxaline group that exerts markedly lower toxicity in animals, compared to its congeners. Here, the pharmacokinetics and metabolism of Cyx after oral (PO), intramuscular (IM), and intravenous (IV) routes of administration were studied to establish safety criteria for the clinical use of Cyx in animals. Six beagle dogs (3 males, 3 females) were administered Cyx through PO (40 mg kg(-1) b.w.), IM (10 mg kg(-1) b.w.), and IV (10 mg kg(-1) b.w.) routes with a washout period of 2 weeks in a crossover design. Highly sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV) was employed for determination of Cyx and its main metabolites, 1, 4-bisdesoxycyadox (Cy1), cyadox-1-monoxide (Cy2), N-(quinoxaline-2-methyl)-cyanide acetyl hydrazine (Cy4), and quinoxaline-2-carboxylic acid (Cy6) in plasma, urine and feces of dogs. The oral bioavailability of Cyx was 4.75%, suggesting first-pass effect in dogs. The concentration vs. time profile in plasma after PO administration indicates that Cyx is rapidly dissociated into its metabolites and eliminated from plasma earlier, compared to its metabolites. The areas under the curve (AUC) of Cyx after PO, IM and IV administration were 1.22 h × μg mL(-1), 6.3 h × μg mL(-1), and 6.66 h × μg mL(-1), while mean resident times (MRT) were 7.32, 3.58 and 0.556 h, respectively. Total recovery of Cyx and its metabolites was >60% with each administration route. In feces, 48.83% drug was recovered after PO administration, while 18.15% and 17.11% after IM and IV injections, respectively, suggesting renal clearance as the major route of excretion with IM and IV administration and feces as the major route with PO delivery. Our comprehensive evaluation of Cyx has uncovered detailed information that should facilitate its judicious use in animals by improving understanding of its pharmacology.

  12. The inhibition of cocaine-induced locomotor activity by CART 55-102 is lost after repeated cocaine administration.

    Science.gov (United States)

    Job, Martin O; Shen, Li L; Kuhar, Michael J

    2013-08-29

    CART peptide is known for having an inhibitory effect on cocaine- and dopamine-mediated actions after acute administration of cocaine and dopamine. In this regard, it is postulated to be a homeostatic, regulatory factor on dopaminergic activity in the nucleus accumbens (NAc). However, there is no data on the effect of CART peptide after chronic administration of cocaine, and this study addresses this. It was found that CART peptide blunted cocaine-induced locomotion (LMA) after acute administration of cocaine, as expected, but it did not affect cocaine-mediated LMA after chronic administration of cocaine. The loss of CART peptide's inhibitory effect did not return for up to 9 weeks after stopping the repeated cocaine administration. It may not be surprising that homeostatic regulatory mechanisms in the NAc are lost after repeated cocaine administration, and that this may be a mechanism in the development of addiction.

  13. Bidirectional Tachycardia after an Acute Intravenous Administration of Digitalis for a Suicidal Gesture

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    Diletta Sabatini

    2014-01-01

    Full Text Available Acute digoxin intoxication is a life-threating condition associated with severe cardiotoxicity. Female gender, age, low lean body mass, hypertension, and renal insufficiency may worsen the prognosis. Arrhythmias caused by digitalis glycosides are characterized by an increased automaticity coupled with concomitant conduction delay. Bidirectional tachycardia is pathognomonic of digoxin intoxication, but it is rarely observed. An 83-year-old woman was admitted to the Emergency Department after self-administration of 5 mg of digoxin i.v. for suicidal purpose. Her digoxin serum concentration was 17.4 ng/mL. The patient developed a bidirectional tachycardia and the Poison Control Center of the hospital provided digoxin immune fab. Bidirectional tachycardia quickly reversed and the patient remained stable throughout the hospital stay. This case shows that a multiple disciplinary approach, involving cardiologists and toxicologists, is essential for the management of digoxin intoxication. The optimal treatment of this rare event depends on the clinical conditions and on the serum drug concentration of the patient. Digoxin immune fab represents a safe, effective, and specific method for rapidly reversing digitalis cardiotoxicity and should be started as soon as the diagnosis is defined.

  14. Penetration of prulifloxacin into gynaecological tissues after single and repeated oral administrations.

    Science.gov (United States)

    Gorlero, Franco; Lorenzi, Paola; Rosignoli, Maria Teresa; Picollo, Rossella; Ruggieri, Alessandro; Barattè, Simona; Dionisio, Paolo

    2007-01-01

    This study aimed to evaluate the penetration into gynaecological tissues of ulifloxacin, the active metabolite of prulifloxacin, a once-daily fluoroquinolone administered once or in repeated doses. This was an open-label, randomised study that included 20 consenting female inpatients (age range 40-65 years) requiring total simple hysterectomy as a result of benign disease. Three groups of patients were enrolled: group A (four patients whose gynaecological tissue samples were used to set up the bioanalytical method); group B (eight patients treated 3 hours before surgery with one 600 mg tablet of prulifloxacin); group C (eight patients treated with prulifloxacin 600 mg once daily for 3 days and undergoing surgery 3 hours after the last dose). Patients to be treated with prulifloxacin were randomly allocated to group B or C. During surgery, samples of blood were collected jointly with healthy tissue removed from the endometrium, proximal fallopian tube, vaginal posterior fornix and portio vaginalis. Ulifloxacin concentrations in plasma and gynaecological tissues were determined by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method. An intrastudy assessment of the bioanalytical method performance was also conducted for plasma and tissues using calibration and quality control data (spiked samples). Ulifloxacin mean concentrations were always higher in group C than in group B patients, both in plasma (0.76 vs 0.53 microg/mL) and in gynaecological tissues, namely fallopian tube (1.38 vs 0.81 microg/g), posterior fornix (1.48 vs 1.05 microg/g), portio vaginalis (1.46 vs 1.45 microg/g) and endometrium (2.20 vs 1.39 microg/g), as expected after repeated drug administrations. Tissue concentrations observed after repeated administrations were generally higher than the ulifloxacin minimum inhibitory concentrations for pathogens more frequently involved in gynaecological bacterial infections. The mean tissue/plasma ratios ranged between 1.5 and

  15. Intravenous or intranasal administration of gliadin is able to down-regulate the specific immune response in mice.

    Science.gov (United States)

    Rossi, M; Maurano, F; Caputo, N; Auricchio, S; Sette, A; Capparelli, R; Troncone, R

    1999-08-01

    The mucosal lesion in coeliac disease (CD) represents an immunologically mediated injury triggered by gliadin and is restricted by a particular assortment of major histocompatibility complex (MHC) class II genes. Therefore, immunomodulatory strategies to tolerize gliadin-specific, class II-restricted T-cell responses could represent an alternative to current treatments of CD, which are based on a gluten-free diet. In this study, BALB/c mice derived from a gluten-free diet colony were tolerized by either intranasal (i.n.) or intravenous (i.v.) administration of single or multiple doses of gliadin. While a single dose failed to induce tolerance, a significant decrease in gliadin-specific T-cell proliferation was detected (P < 0.001) after multiple i.n. or i.v. administrations. No significant difference in antibody titre was detected for antigen-specific immunoglobulin G (IgG) or the IgG1 subclass, but a lower IgG2a-specific titre was observed. Both interferon-gamma (IFN-gamma) and interleukin (IL)-2 expression, measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR), were reduced on antigen administration, both i.v. and i.n. Neither regimen showed a regulatory effect on IL-4 production. As T helper 1 (Th1) cytokines seem to be important in the pathogenesis of CD, our data therefore highlight the potential of i.n. and i.v. routes for the design of useful immunomodulatory strategies for CD.

  16. Efficacy,safety and tolerance of continuous erythropoietin receptor activator intravenous administration on anemia correction in dialysis patients with chronic renal anemia

    Institute of Scientific and Technical Information of China (English)

    钱家麒

    2013-01-01

    Objective To evaluate the efficacy,safety and toler-ance of continuous erythropoietin receptor activator(CE-RA) once every 2 weeks intravenous injection on anemia correction in dialysis patients compared to Epoetin-β(EPO-β) administration. Methods An open label,

  17. The first report of treatment of liver abscess due to Candida albicans with intra-abscess and intravenous administration of liposomal amphotericin B (Amphotec)

    Institute of Scientific and Technical Information of China (English)

    LIAO Wan-qing; YAO Zhi-rong; WEN Hai; XU Hong; YANG Song-lin; LIU Xing-hua; TAN Wei-ping

    2005-01-01

    Increasing reports on application and safety of liposomal amphotericin B (Amphotec) in the treatment of deep fungal infections have been described recently. This is the first report that a case of liver abscess due to Candida albicans was completely cured with intra-abscess and intravenous administration of liposomal amphotericin B without recurrence in three-year follow-up period.

  18. Comparison of the effects of lidocaine pre-administration and local warming of the intravenous access site on propofol injection pain: Randomized, double-blind controlled trial.

    Science.gov (United States)

    Jeong, Meejeong; Yoon, Haesang

    2016-09-01

    Lidocaine reduces pain that occurs upon the intravenous injection of propofol. But, there are few non-pharmacological nursing interventions to reduce propofol injection pain. To compare the effects of lidocaine pre-administration and local warming of the intravenous access site on propofol injection pain. Prospective, double-blind, randomized controlled trial. The 555 bed, non-teaching National Cancer Center in Kyunggido, South Korea. A total of 96 patients who underwent thyroidectomy under total intravenous general anesthesia with propofol were randomly allocated to the control, lidocaine pre-administration (LA) or local warming (LW) group. All three groups received 2% propofol with an effect-site target at 3μg/mL for induction dose. The control group received 2% propofol with no intervention. The lidocaine pre-administration group received 2% propofol 30s after 1% lidocaine 30mg. The local warming group received 2% propofol after warming of the intravenous access site for 1min using 43°C forced air. Propofol injection pain was assessed by four-point verbal categorial scoring (VCS), numerical rating scale (NRS) and surgical pleth index (SPI). Pain VCS of the LA group (mean±SD, 1.11±0.45) was significantly reduced (U=-3.92, plidocaine pre-administration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Distribution and excretion of arsenic in cynomolgus monkey following repeated administration of diphenylarsinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Yayoi [National Institute for Environmental Studies, Environmental Health Sciences Division, Tsukuba, Ibaraki (Japan); Negishi, Takayuki [Aoyama Gakuin University, Department of Chemistry and Biological Science, Tokyo (Japan); Mizumura, Ayano; Watanabe, Takayuki [Chiba University, Graduate School of Pharmaceutical Sciences, Chiba (Japan); Hirano, Seishiro [Chiba University, Graduate School of Pharmaceutical Sciences, Chiba (Japan); National Institute for Environmental Studies, Research Center for Environmental Risk, Tsukuba, Ibaraki (Japan)

    2008-08-15

    Diphenylarsinic acid (DPAA), a possible product of degradation of arsenic-containing chemical weapons, was detected in well water in Kamisu City, Ibaraki Prefecture, Japan, in 2003. Although some individuals in this area have been affected by drinking DPAA-containing water, toxicological findings on DPAA are limited. To elucidate the mechanism of its toxicity, it is necessary to determine the metabolic behavior of DPAA in the body. In this study, pregnant cynomolgus monkeys at the 50th day of pregnancy were used. The monkeys were treated daily with 1.0 mg DPAA/kg body weight using a nasogastric tube, and the distribution and excretion of arsenic were examined after the repeated administration and 198-237 days after the last administration of DPAA. Fecal excretion was higher than urinary excretion (ca. 3:2 ratio), and arsenic accumulated in the hair and erythrocytes. Distribution of DAPP to plasma and hemolyzed erythrocytes was also examined by high-performance liquid chromatography-inductively coupled argon plasma mass spectrometry (HPLC-ICP MS). Two peaks were found in the elution profile of arsenic, due to free and probably protein-bound DPAA. The protein-bound arsenic compounds were presumably trivalent diphenylarsenic compounds, since free DPAA was recovered after treatment of heat-denatured samples with hydrogen peroxide. (orig.)

  20. [Repeated perioperative administration of fructose and sorbitol in a female patient with hereditary fructose intolerance [HFI)].

    Science.gov (United States)

    Sachs, M; Asskali, F; Förster, H; Encke, A

    1993-03-01

    The present paper reports on an adult female patient whose hereditary fructose intolerance (HFI) was at first not diagnosed and who, within the space of 2 years after repeated elective surgery and the perioperative administration of fructose and sorbitol, developed "hepatic and renal failure of unclear origin." At a later stage we were able to establish the diagnosis of HFI by means of a fructose tolerance test in both she and her brother, for whom intolerance to fruit and desserts had been known since early childhood. In addition, literature references to fatalities following the parenteral application of fructose and sorbitol were analyzed. During the course of fructose infusion in both the patient and her brother with HFI, the following metabolic changes were noted: hypoglycemia, elevated rise in the blood fructose concentration, hyperlactacidemia, elevated rise in the blood fructose concentration, hyperlactacidemia, and hyperammonemia. These metabolic changes proved to be reversible after discontinuing the fructose infusion. Analysis of the literature on the fatalities following parenteral fructose administration established that fruit and dessert intolerance was known for all collated patients with HFI, and that, clearly, no regular metabolic tests had been conducted.

  1. Intravenous administration of achyranthes bidentata polypeptides supports recovery from experimental ischemic stroke in vivo.

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    Hongmei Shen

    Full Text Available BACKGROUND: Achyranthes bidentata Blume (A. bidentata is a commonly prescribed Chinese medicinal herb. A. bidentata polypeptides (ABPP is an active composite constituent, separated from the aqueous extract of A. bidentata. Our previous studies have found that ABPP have the neuroprotective function in vitro and in rat middle cerebral artery occlusion (MCAO model in attenuating the brain infract area induced by focal ischemia-reperfusion. However, the ultimate goal of the stroke treatment is the restoration of behavioral function. Identifying behavioral deficits and therapeutic treatments in animal models of ischemic stroke is essential for potential translational applications. METHODOLOGY AND PRINCIPAL FINDINGS: The effect of ABPP on motor, sensory, and cognitive function in an ischemic stroke model with MCAO was investigated up to day 30. The function recovery monitored by the neurological deficit score, grip test, body asymmetry, beam-balancing task, and the Morris Water Maze. In this study, systemic administration of ABPP by i.v after MCAO decreased the neurological deficit score, ameliorated the forepaw muscle strength, and diminished the motor and sensory asymmetry on 7(th and 30(th day after MCAO. MCAO has been observed to cause prolonged disturbance of spatial learning and memory in rats using the MWM, and ABPP treatment could improve the spatial learning and memory function, which is impaired by MCAO in rats, on 30(th day after MCAO. Then, the viable cells in CA1 region of hippocampus were counted by Nissl staining, and the neuronal cell death were significantly suppressed in the ABPP treated group. CONCLUSION: ABPP could improve the recovery of sensory, motor and coordination, and cognitive function in MCAO-induced ischemic rats. And this recovery had a good correlation to the less of neuronal injury in brain.

  2. Menthol facilitates the intravenous self-administration of nicotine in rats

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    Tengfei eWang

    2014-12-01

    Full Text Available Menthol is preferred by approximately 25% of smokers and is the most common flavoring additive in tobacco and electronic cigarettes. Although some clinical studies have suggested that menthol facilitates the initiation of smoking and enhances the dependence on nicotine, many controversies remain. Using licking as the operant behavior, we found that adolescent rats self-administering nicotine (30 μg/kg/infusion, free base, i.v. with contingent oral menthol (60 μl, 0.01% w/v obtained significantly more infusions than rats receiving a vehicle cue or rats self-administering i.v. saline with a menthol cue. Rats yoked to their menthol-nicotine masters emitted significantly fewer licks on the active spouts, indicating that contingent pairing between nicotine and menthol is required for sustained nicotine intake. Rats that self-administered nicotine with a menthol cue also exhibited a long-lasting extinction burst and robust reinstatement behavior, neither of which were observed in rats that self-administered saline with a menthol cue. The cooling sensation of menthol is induced by activating the transient receptor potential M8 (TRPM8 channel. When WS-23, an odorless agonist of the TRPM8 channel, was used as a contingent cue for nicotine, the rats obtained a similar number of nicotine infusions as the rats that were provided a menthol cue and exhibited a strong preference for the active spout. In contrast, highly appetitive taste and odor cues failed to support nicotine self-administration. These data indicated that menthol, likely by inducing a cooling sensation, becomes a potent conditioned reinforcer when it is contingently delivered with nicotine. Together, these results provide a key behavioral mechanism by which menthol promotes the use of tobacco products or electronic cigarettes.

  3. The effect of giving detailed information about intravenous radiopharmaceutical administration on the anxiety level of patients who request more information.

    Science.gov (United States)

    Kaya, Eser; Ciftci, Ismail; Demirel, Reha; Cigerci, Yeliz; Gecici, Omer

    2010-02-01

    Nuclear medicine procedures use radiopharmaceuticals, which produce radiation and potential adverse reactions, albeit at a low rate. It is the patient's ethical, legal, and medical right to be informed of the potential side effects of procedures applied to them. Our purpose was to determine the effect of providing information about intravenous radiopharmaceutical administration on the anxiety level of patients who request more information. This study was completed in two separate Nuclear Medicine Departments. The study included 620 (247 M, 373 F) patients who had been referred for myocardial perfusion, bone, dynamic renal, and thyroid scintigraphic examinations. The patients were divided into two groups according to whether they requested more information or not. Group 1 consisted of 388 patients who wanted to receive more information about the procedure, while Group 2 consisted of 232 patients who did not request additional information. The State-Trait Anxiety Inventory (STAI-S and STAI-T) was used to determine a patient's anxiety level. After simple information was given, state and trait anxiety levels were measured in both groups. We gave detailed information to the patients in Group 1 and then measured state anxiety again. Detailed information included an explanation of the radiopharmaceutical risk and probable side effects due to the scan procedure. There was no statistical difference between Groups 1 and 2 in STAI-T or STAI-S scores after simple information was given (p = 0.741 and p = 0.945, respectively). The mean value of STAI-S score was increased after the provision of detailed information and there was a statistically significant difference between after simple information SATI-S and after detailed information STAI-S (p information, while there was no change in 32 patients. After detailed information, the greatest increase in STAI-S score was seen in the myocardial perfusion scan patients, when evaluating according to scan procedure (p Informed consent

  4. Stereoselective pharmacokinetic analysis of tramadol and its main phase I metabolites in healthy subjects after intravenous and oral administration of racemic tramadol.

    Science.gov (United States)

    García Quetglas, Emilio; Azanza, Jose Ramón; Cardenas, Ernesto; Sádaba, Belén; Campanero, Miguel Angel

    2007-01-01

    The kinetics of tramadol enantiomers are stereoselective when doses of the racemic drug are given orally. To document whether the route of administration determines the stereoselective kinetics of tramadol enantiomers, healthy volunteers received 100 mg oral or intravenous doses of racemic tramadol, and serial blood samples were obtained to assay tramadol enantiomers and their main phase I metabolites, O-demethyltramadol and N-demethyltramadol. To assess accurately the involvement of their metabolites in the pharmacokinetics of tramadol, it is essential to determine the rate and extent of the formation of the enantiomers of these metabolites. A simultaneous pharmacokinetic model describing the plasma concentration-curves of the generated metabolites and the parent compounds after intravenous and oral drug administration is developed and presented. Tramadol and O-demethyltramadol were the major compounds detected in plasma after intravenous administration. Nevertheless, the N-demethylation of tramadol showed a significant increase when the oral route was used. After both oral and intravenous doses, the kinetics of the tramadol enantiomers were stereoselective. The AUC for (R )-(+)-tramadol was greater than the AUC for (S)-(-)-tramadol. The formation of N-demethyltramadol also was enantioselective after oral administration of racemic tramadol, with a greater AUC for (R)-(+)-N-demethyltramadol than for (S)-(-)-N-demethyltramadol. In the opposite form, (S)-(-)-O-demethyltramadol was formed faster than (R)-(+)-O-demethyltramadol. The metabolism of tramadol was also route-dependent with a different enantiomeric ratio for tramadol and its main phase I metabolites after intravenous and oral administration. The disposition of N-demethyltramadol was concentration-dependent.

  5. Intravenous Administration of Adipose-Derived Stem Cell Protein Extracts Improves Neurological Deficits in a Rat Model of Stroke

    Science.gov (United States)

    Zhao, Kai; Li, Rui; Gu, Changcong; Liu, Long; Jia, Yulong; Guo, Xize; Zhang, Wanping; Pei, Chunying; Tian, Linlu; Li, Bo; Jia, Jianrong; Cheng, Huakun

    2017-01-01

    Treatment of adipose-derived stem cell (ADSC) substantially improves the neurological deficits during stroke by reducing neuronal injury, limiting proinflammatory immune responses, and promoting neuronal repair, which makes ADSC-based therapy an attractive approach for treating stroke. However, the potential risk of tumorigenicity and low survival rate of the implanted cells limit the clinical use of ADSC. Cell-free extracts from ADSC (ADSC-E) may be a feasible approach that could overcome these limitations. Here, we aim to explore the potential usage of ADSC-E in treating rat transient middle cerebral artery occlusion (tMCAO). We demonstrated that intravenous (IV) injection of ADSC-E remarkably reduces the ischemic lesion and number of apoptotic neurons as compared to other control groups. Although ADSC and ADSC-E treatment results in a similar degree of a long-term clinical beneficial outcome, the dynamics between two ADSC-based therapies are different. While the injection of ADSC leads to a relatively mild but prolonged therapeutic effect, the administration of ADSC-E results in a fast and pronounced clinical improvement which was associated with a unique change in the molecular signature suggesting that potential mechanisms underlying different therapeutic approach may be different. Together these data provide translational evidence for using protein extracts from ADSC for treating stroke.

  6. Intravenous Administration of Adipose-Derived Stem Cell Protein Extracts Improves Neurological Deficits in a Rat Model of Stroke

    Directory of Open Access Journals (Sweden)

    Kai Zhao

    2017-01-01

    Full Text Available Treatment of adipose-derived stem cell (ADSC substantially improves the neurological deficits during stroke by reducing neuronal injury, limiting proinflammatory immune responses, and promoting neuronal repair, which makes ADSC-based therapy an attractive approach for treating stroke. However, the potential risk of tumorigenicity and low survival rate of the implanted cells limit the clinical use of ADSC. Cell-free extracts from ADSC (ADSC-E may be a feasible approach that could overcome these limitations. Here, we aim to explore the potential usage of ADSC-E in treating rat transient middle cerebral artery occlusion (tMCAO. We demonstrated that intravenous (IV injection of ADSC-E remarkably reduces the ischemic lesion and number of apoptotic neurons as compared to other control groups. Although ADSC and ADSC-E treatment results in a similar degree of a long-term clinical beneficial outcome, the dynamics between two ADSC-based therapies are different. While the injection of ADSC leads to a relatively mild but prolonged therapeutic effect, the administration of ADSC-E results in a fast and pronounced clinical improvement which was associated with a unique change in the molecular signature suggesting that potential mechanisms underlying different therapeutic approach may be different. Together these data provide translational evidence for using protein extracts from ADSC for treating stroke.

  7. Comparative pharmacokinetics of enrofloxacin, danofloxacin, and marbofloxacin after intravenous and oral administration in Japanese quail (Coturnix coturnix japonica).

    Science.gov (United States)

    Haritova, Aneliya; Dimitrova, Dimitrichka; Dinev, Toncho; Moutafchieva, Rumyana; Lashev, Lubomir

    2013-03-01

    A population approach was used to evaluate the pharmacokinetic parameters of 3 fluoroquinolones administered to Japanese quail (Coturnix coturnix japonica). Healthy adult quail (n = 50) were divided into 3 groups, each administered a separate intravenous and oral dose of the compounded drug: enrofloxacin at 10 mg/kg (n = 18; 9 male, 9 female), danofloxacin at 10 mg/kg (n = 12; 6 male, 6 female), and marbofloxacin at 5 mg/kg (n = 20; 10 male, 10 female). A fourth group was used as a control (n = 5). Enrofloxacin was metabolized extensively to ciprofloxacin, while no metabolites of either danofloxacin or marbofloxacin were detected. The volume of distribution was high, greater than 1 in all cases, and highest for danofloxacin, followed by enrofloxacin, then marbofloxacin. The total body clearance was higher in quail than that reported for other avian species with the exception of ostriches. As in mammals, the lowest clearance rate of the 3 fluoroquinolones was observed for marbofloxacin. Enrofloxacin was absorbed most rapidly, followed by marbofloxacin, then danofloxacin. The highest bioavailability was observed for danofloxacin followed by marbofloxacin, while very low bioavailability with significant conversion to ciprofloxacin was observed for enrofloxacin. Population analysis showed low intersubject variability for danofloxacin and marbofloxacin in contrast to that for enrofloxacin and its main metabolite, ciprofloxacin. Because of their more favorable pharmacokinetic properties after oral administration, either danofloxacin or marbofloxacin appears to be preferable to enrofloxacin for the treatment of susceptible bacterial infection in Japanese quail.

  8. Clinical efficacy of intravenous administration of marbofloxacin in a Staphylococcus aureus infection in tissue cages in ponies.

    Science.gov (United States)

    Voermans, M; van Soest, J M; van Duijkeren, E; Ensink, J M

    2006-12-01

    Tissue cages (TC), implanted subcutaneously in the neck in eight ponies, were inoculated with Staphylococcus aureus (S. aureus) to determine the clinical efficacy of marbofloxacin in the treatment of this infection. From 21 h after inoculation, marbofloxacin (6 mg/kg) was administered intravenously (i.v.) once daily for 7 days. Samples of the tissue cage fluid (TCF) were taken to determine marbofloxacin concentrations (days 1, 3 and 7), using high-pressure liquid chromatography, and numbers of viable bacteria [colony forming units (CFU)] (days 1, 3, 7, 14 and 21). Statistical analysis was used to compare CFU before and after treatment. Clinical signs and CFU were used to evaluate the efficacy of treatment. Although, there was a slight decrease in CFU in all TC initially, the infection was not eliminated by marbofloxacin treatment in any of the ponies and abscesses formed. As the MIC (0.25 microg/mL) did not change during treatment and the concentration of marbofloxacin during treatment (mean concentration in TCF was 0.89 microg/mL on day 1, 0.80 microg/mL on day 3 and 2.77 microg/mL on day 7) was above MIC, we consider that the treatment failure might be attributable to the formation of a biofilm by S. aureus. Based on the present results, i.v. administration of marbofloxacin alone is not suitable for the elimination of S. aureus infections from secluded sites.

  9. Subcutaneous vs intravenous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy: an Italian cost-minimization analysis.

    Science.gov (United States)

    Lazzaro, Carlo; Lopiano, Leonardo; Cocito, Dario

    2014-07-01

    Prior researches have suggested that home-based subcutaneous immunoglobulin (SCIG) is equally effective and can be less expensive than hospital-based intravenous immunoglobulin (IVIG) in treating chronic inflammatory demyelinating polyneuropathy (CIDP) patients. This economic evaluation aims at comparing costs of SCIG vs IVIG for CIDP patients in Italy. A 1-year model-based cost-minimization analysis basically populated via neurologists' opinion was undertaken from a societal perspective. Health care resources included immunoglobulin; drugs for premedication and complications (rash, headache, and hypertension) management; time of various health care professionals; pump for SCIG self-administration; infusion disposables. Non-health care resources encompassed transport and parking; losses of working and leisure time for patients and caregivers. Unit or yearly costs for resources valuation were mainly obtained from published sources. Costs were expressed in Euro () 2013. An extensive one-way sensitivity analysis (OWSA) and a scenario SA tested the robustness of the base case findings. Overall costs per patient amount to 49,534.75 (SCIG) and 50,895.73 (IVIG); saving in favour of SCIG reaches 1360.98. For both SCIG and IVIG, the cost driver was immunoglobulin (94.06 vs 86.06 % of the overall costs, respectively). Sensitivity analyses confirmed the consistency of the baseline results. SCIG may be a cost-saving therapy for Italian CIDP patients.

  10. Repeated otilonium bromide administration prevents neurotransmitter changes in colon of rats underwent to wrap restraint stress.

    Science.gov (United States)

    Traini, Chiara; Evangelista, Stefano; Girod, Vincent; Faussone-Pellegrini, Maria Simonetta; Vannucchi, Maria Giuliana

    2017-04-01

    Otilonium bromide (OB) is a spasmolytic drug successfully used for the treatment of irritable bowel syndrome (IBS). Its efficacy has been attributed to the block of L- and T-type Ca(2+) channels and muscarinic and tachykinin receptors in the smooth muscle. Furthermore, in healthy rats, repeated OB administration modified neurotransmitter expression and function suggesting other mechanisms of action. On this basis, we investigated whether repeated OB treatment prevented the functional and neurochemical changes observed in the colon of rats underwent to wrap restrain stress (WRS) a psychosocial stressor considered suitable to reproduce the main IBS signs and symptoms. In control, WRS and OB/WRS rats functional parameters were measured in vivo and morphological investigations were done ex vivo in the colon. The results showed that OB counteracts most of the neurotransmitters changes caused by WRS. In particular, the drug prevents the decrease in SP-, NK1r-, nNOS-, VIP-, and S100β-immunoreactivity (IR) and the increase in CGRP-, and CRF1r-IR. On the contrary, OB does not affect the increase in CRF2r-IR neurons observed in WRS rats and does not interfere with the mild mucosal inflammation due to WRS. Finally, OB per se increases the Mr2 expression in the muscle wall and decreases the number of the myenteric ChAT-IR neurons. Functional findings show a significantly reduction in the number of spontaneous abdominal contraction in OB treated rats. The ability of OB to block L-type Ca(2+) channels, also expressed by enteric neurons, might represent a possible mechanism through which OB exerts its actions. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  11. Intravenous fluid administration may improve post-operative course of patients with chronic subdural hematoma: a retrospective study.

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    Miroslaw Janowski

    Full Text Available BACKGROUND: The treatment of chronic subdural hematoma (cSDH is still charged of significant risk of hematoma recurrence. Patient-related predictors and the surgical procedures themselves have been addressed in many studies. In contrast, postoperative management has infrequently been subjected to detailed analysis. Moreover variable intravenous fluid administration (IFA was not reported in literature till now in the context of cSDH treatment. METHODOLOGY/PRINCIPAL FINDINGS: A total of 45 patients with cSDH were operated in our department via two burr hole craniostomy within one calendar year. Downward drainage was routinely left in hematoma cavity for a one day. Independent variables selected for the analysis were related to various aspects of patient management, including IFA. Two dependent variables were chosen as measure of clinical course: the rate of hematoma recurrence (RHR and neurological status at discharge from hospital expressed in points of Glasgow Outcome Scale (GOS. Univariate and multivariate regression analyses were performed. Hematoma recurrence with subsequent evacuation occurred in 7 (15% patients. Univariate regression analysis revealed that length of IFA after surgery influenced both dependent variables: RHR (p = 0.045 and GOS (p = 0.023. Multivariate regression performed by backward elimination method confirmed that IFA is a sole independent factor influencing RHR. Post hoc dichotomous division of patients revealed that those receiving at least 2000 ml/day over 3 day period revealed lower RHR than the group with less intensive IFA. (p = 0.031. CONCLUSIONS/SIGNIFICANCE: IFA has been found to be a sole factor influencing both: RHR and GOS. Based on those results we may recommend administration of at least 2000 ml per 3 days post-operatively to decrease the risk of hematoma recurrence.

  12. The metabolic disposition of /sup 14/C-labelled carmoisine in the rat after oral and intravenous administration

    Energy Technology Data Exchange (ETDEWEB)

    Galli, C.L.; Marinovich, M.; Costa, L.G.

    1982-08-01

    The absorption, distribution and excretion of the red azo dye carmoisine (Ext. D and C No. 10) was studied in male rats. (/sup 14/C)Carmoisine was administered in a dose of 200 mg/kg (25 microCi) by gavage or in the same dose (200 mg/kg; 3 microCi) by intravenous injection, and radioactivity was measured in blood, tissue, faeces and urine at different times after dosing. After oral administration of the dye, no radioactivity was detected in the brain, adipose tissue, muscle, testes, spleen or lung, and recovery of the administered activity in faeces and urine was almost complete by 32 hr. The radioactivity profile of the blood indicated rapid but poor absorption of (/sup 14/C)carmoisine, a maximum radioactivity content corresponding to 0.01% of the dose per ml of blood being reached within 10 min. The decay curve for /sup 14/C radioactivity in the blood after iv injection of (/sup 14/C)carmoisine indicated rapid distribution to the tissues and could be described in terms of a two-compartment mathematical model. The highest levels of radioactivity occurred in the gastro-intestinal tract and liver after the injection but after 24 hr no radioactivity was detectable in these or other tissues. All the radioactivity was recovered in the faeces and urine in the 24 hr following iv injection, the 79% of the dose present in faeces indicating active excretion of the dye and its metabolites in the bile and poor reabsorption from the intestine. The bioavailability of (/sup 14/C)carmoisine, calculated from the blood-radioactivity curves after oral and iv administration, was less than 10%.

  13. Pharmacokinetics of amoxicillin/clavulanic acid combination and of both drugs alone after intravenous administration to goats.

    Science.gov (United States)

    Escudero, E; Carceles, C M; Vicente, S

    1996-09-01

    The pharmacokinetic behaviour of an amoxicillin/clavulanic acid combination (25 mg kg-1), and both drugs alone (amoxicillin 20 mg kg-1), clavulanic acid 5 mg kg-1), was studied after intravenous (i.v.) administration of single doses of 10 goats. The objective was to determine whether there were differences in the plasma kinetics of these drugs when administered in combination or alone. The plasma concentration-time data were analysed by compartmental pharmacokinetics and non-compartmental methods. The disposition curves for both drugs alone and in combination were best described by a biexponential equation (two-compartment open model). The elimination half-lives of amoxicillin were 1.05 +/- 0.09 h alone and 1.13 +/- 0.19 h in combination, and those of clavulanic acid were 0.87 +/- 0.07 h and 0.85 +/- 0.09 h, respectively. The apparent volumes of distribution of amoxicillin and clavulanic acid were similar in the two treatments. Body clearances of amoxicillin were 0.12 +/- 0.01 l h-1.kg alone and 0.11 +/- 0.01 l h-1.kg in combination, and of clavulanic acid were 0.12 +/- 0.02 l h-1.kg alone and 0.12 +/- 0.01 l h-1.kg in combination with amoxicillin. The half-lives and body clearances of amoxicillin and clavulanic acid did not differ significantly when administered alone and in combination. It was concluded that the i.v. administration of amoxicillin and clavulanic acid as a combination product did not alter the disposition kinetics of either drug.

  14. Intravenous ethanol infusions can mimic the time course of breath alcohol concentrations following oral alcohol administration in healthy volunteers.

    Science.gov (United States)

    Ramchandani, Vijay A; Plawecki, Martin; Li, Ting-Kai; O'Connor, Sean

    2009-05-01

    Our previous studies have used intravenous (IV) clamping methods to demonstrate that family history positive (FHP) subjects exhibit a greater initial response to alcohol than family history negative (FHN) subjects. These results differ from other studies of family history of alcoholism (FHA) influences, most of which have used an oral alcohol challenge, suggesting that the route of administration may influence both the response to alcohol and FHA-related differences in response. To examine this possibility, one approach would be to directly compare responses following oral and IV alcohol administration in the same subjects. There is, however, a 3- to 4-fold variance, between- and within-subjects, in the breath alcohol concentrations (BrACs) following oral alcohol administration. Thus, our objective was to characterize the between-subject variability in the time course of BrACs following oral alcohol administration in healthy volunteers and to develop an IV infusion method to mimic the BrAC-time course attained following oral alcohol in the same subject. This was a 2-session study in young adult, healthy, nondependent drinkers. In the first session, subjects ingested an oral dose of alcohol, based on total body water, to achieve a target peak BrAC of 80 mg%. In the second session, subjects received an IV infusion of ethanol designed to achieve the same BrAC time course as that achieved in the first session. The individualized infusion-rate profile was precomputed using a physiologically-based pharmacokinetic (PBPK) model for alcohol with model parameters adjusted to the individual's physiology. The peak BrACs (C(max)), times of peak BrAC (T(max)), and the areas under the BrAC vs. time curve (AUC) were compared between sessions to assess how closely the BrAC exposure during the IV infusion session mimicked the exposure following oral alcohol. The time course of BrACs following oral alcohol administration showed a high degree of between-subject variability. Mean C

  15. 临床静脉给药存在的问题分析与对策%Problem analysis and countermeasures for intravenous administration

    Institute of Scientific and Technical Information of China (English)

    张建中; 陈晔; 吴永佩

    2012-01-01

    目的:通过对医院临床静脉给药过程中存在的问题进行分析,寻找安全使用静脉药物的策略.方法:对医院静脉给药过程中存在的两大主要问题:给药错误、输液污染,举例并对成因进行分析.结论:通过完善医院给药系统,改变给药流程,让药师参与到药品使用环节中,采用新科技产品等诸多手段,可有效减少给药错误,确保医院静脉用药的安全.%Objective: To analyze the problems of intravenous administration, and look for effective strategies to ensure safe use of intravenous medications. Methods: There were two main problems in intravenous administration process, named medication errors and infusion contamination. We analyzed the causes of these two problems by case discussion. Conclusions: Through improving hospital delivery system, tailoring administration process, involving pharmacists in medication use process, using new technology products and many other tools, we could effectively reduce medication errors; ensure intravenous medication use safety in hospital.

  16. Comparison of intrapulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and colistin after aerosol delivery and intravenous administration of CMS in critically ill patients.

    Science.gov (United States)

    Boisson, Matthieu; Jacobs, Matthieu; Grégoire, Nicolas; Gobin, Patrice; Marchand, Sandrine; Couet, William; Mimoz, Olivier

    2014-12-01

    Colistin is an old antibiotic that has recently gained a considerable renewal of interest for the treatment of pulmonary infections due to multidrug-resistant Gram-negative bacteria. Nebulization seems to be a promising form of administration, but colistin is administered as an inactive prodrug, colistin methanesulfonate (CMS); however, differences between the intrapulmonary concentrations of the active moiety as a function of the route of administration in critically ill patients have not been precisely documented. In this study, CMS and colistin concentrations were measured on two separate occasions within the plasma and epithelial lining fluid (ELF) of critically ill patients (n = 12) who had received 2 million international units (MIU) of CMS by aerosol delivery and then intravenous administration. The pharmacokinetic analysis was conducted using a population approach and completed by pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulations. The ELF colistin concentrations varied considerably (9.53 to 1,137 mg/liter), but they were much higher than those in plasma (0.15 to 0.73 mg/liter) after aerosol delivery but not after intravenous administration of CMS. Following CMS aerosol delivery, typically, 9% of the CMS dose reached the ELF, and only 1.4% was presystemically converted into colistin. PK-PD analysis concluded that there was much higher antimicrobial efficacy after CMS aerosol delivery than after intravenous administration. These new data seem to support the use of aerosol delivery of CMS for the treatment of pulmonary infections in critical care patients.

  17. Histopathological confirmation of similar intramucosal distribution of fluorescein in both intravenous administration and local mucosal application for probe-based confocal laser endomicroscopy of the normal stomach.

    Science.gov (United States)

    Nonaka, Kouichi; Ohata, Ken; Ban, Shinichi; Ichihara, Shin; Takasugi, Rumi; Minato, Yohei; Tashima, Tomoaki; Matsuyama, Yasushi; Takita, Maiko; Matsuhashi, Nobuyuki; Neumann, Helmut

    2015-12-16

    Probe-based confocal laser endomicroscopy (pCLE) is capable of acquiring in vivo magnified cross-section images of the gastric mucosa. Intravenous injection of fluorescein sodium is used for confocal imaging. However, it is still under debate if local administration of the dye to the mucosa is also effective for confocal imaging as it is not yet clear if topical application also reveals the intramucosal distribution of fluorescein. The objective of this study was to evaluate the intramucosal distribution of fluorescein sodium after topical application and to compare the distribution to the conventional intravenous injection used for confocal imaging. pCLE of the stomach uninfected with Helicobacter pylori was performed in a healthy male employing intravenous administration and local mucosal application of fluorescein. The mucosa of the lower gastric body was biopsied 1 min and 5 min after intravenous administration or local mucosal application of fluorescein, and the distribution of fluorescein in the biopsy samples was examined histologically. Green fluorescence was already observed in the cytoplasm of fundic glandular cells in the biopsied deep mucosa 1 min after local mucosal application of fluorescein. It was also observed in the foveolar lumen and inter-foveolar lamina propria, although it was noted at only a few sites. In the tissue biopsied 5 min after the local mucosal application of fluorescein, green fluorescence was more frequently noted in the cytoplasm of fundic glandular cells than in that 1 min after the local mucosal application of fluorescein, although obvious green fluorescence was not identified in the foveolar lumen or inter-foveolar lamina propria. The distribution of intravenously administered fluorescein in the cytoplasm of fundic glandular cells was also clearly observed similarly to that after local mucosal application of fluorescein. Green fluorescence in more cells was observed in many cells 5 min after intravenous administration compared

  18. Pharmacokinetics of marbofloxacin in lactating cows after repeated intramuscular administrations and pharmacodynamics against mastitis isolated strains.

    Science.gov (United States)

    Schneider, M; Vallé, M; Woehrlé, F; Boisramé, B

    2004-01-01

    The plasma and milk pharmacokinetics of marbofloxacin, a fluoroquinolone antibacterial compound, were evaluated in dairy cows, as well as its pharmacodynamic characteristics against mastitis-isolated pathogens. Marbofloxacin was given intramuscularly as a 10% aqueous solution to dairy cows either at a single dose or at repeated doses of 2 mg/kg once daily for 3 d. Blood and milk samples were collected for the determination of the concentration of marbofloxacin and of its putative metabolites: N-desmethyl-marbofloxacin and N-oxide-marbofloxacin. Bacterial field isolates were from milk samples collected from dairy cows suspected of having an intramammary infection. After identification, the minimal inhibitory concentration (MIC) was determined against the isolated strains. The maximal marbofloxacin concentration (Cmax) observed in milk after the first administration was 1.024 microg/mL, and the area under the curve during the first dosing interval was 6.513 microg/h per milliliter. After the third administration, these parameters were slightly increased (about 20% at most). Both metabolites were detected in the milk, but their concentrations were below the limit of quantification. The MIC against 90% of the population (MIC90) of Escherichia coli was 0.016 microg/mL, and it was 0.229 microg/mL against Staphylococcus aureus. The following surrogate clinical outcome markers were obtained against E. coli strains: a Cmax/MIC ratio of 67 and an area under the curve/MIC ratio of 407 h. Hence, a possible efficacy of marbofloxacin in the treatment of E. coli-induced mastitis could be expected as the endpoints of 10 and 250 h, respectively, are reached.

  19. Comparative disposition of 2,3-epoxy-1-propanol (glycidol) in rats following oral and intravenous administration.

    Science.gov (United States)

    Nomeir, A A; Silveira, D M; Ferrala, N F; Markham, P M; McComish, M F; Ghanayem, B I; Chadwick, M

    1995-02-01

    Glycidol (2,3-epoxy-1-propanol), an industrial chemical, has been shown to be a reproductive toxicant in short-term studies and a carcinogen in rats and mice in oncogenicity studies. The reproductive toxicity of glycidol was believed to result from its conversion to alpha-chlorohydrin by the action of HCl in the stomach. The comparative disposition of glycidol was investigated in rats following oral (po) or intravenous (iv) administration at doses of 37.5 and 75 mg/kg. These were the doses used in the National Toxicology Program (NTP) oncogenicity study with glycidol. Approximately 87-92% of the dose was absorbed from the gastrointestinal tract of the rat. [14C]Glycidol equivalents were eliminated in urine (40-48% of dose in 72 h), feces (5-12%), and exhaled as CO2 (26-32%). At both doses, 9-12% and 7-8% (estimated) of the dose remained in tissues at 24 and 72 h following dosing, respectively. In general, the concentrations of glycidol equivalents in tissues were proportional to the dose. The highest concentrations of radioactivity were observed in blood cells, thyroid, liver, kidney, and spleen, and the lowest in adipose tissue, skeletal muscle, and plasma. The pattern of distribution of radioactivity in tissues was similar for both the iv and po routes. The total recovery of radioactivity ranged from 87 to 91% of dose. Urinary radioactivity was resolved by high-performance liquid chromatography (HPLC) analysis into 15 metabolites. There were one major (14-21% of the dose) and four lesser metabolites (each representing 2-8%); the others were minor, each representing 1% or less of the dose. In general, the urinary metabolic profile was similar following either iv or po administration at the two doses studied. Previous studies by other investigators suggested that alpha-chlorohydrin, which was presumably formed from glycidol by the HCl in the stomach, was metabolized and excreted in urine as beta-chlorolactic acid. The results of the present study show that very

  20. Prevalence of NSF following intravenous gadolinium-contrast media administration in dialysis patients with endstage renal disease

    Energy Technology Data Exchange (ETDEWEB)

    Heinz-Peer, Gertraud, E-mail: gertraud.heinz@meduniwien.ac.a [Department of Radiology, Medical University of Vienna (Austria); Neruda, Anita [Department of Radiology, Medical University of Vienna (Austria); Watschinger, Bruno; Vychytil, Andreas [Department of Nephrology, Medical University of Vienna (Austria); Geusau, Alexandra [Department of Dermatology, Medical University of Vienna (Austria); Haumer, Markus [Department of Internal Medicine II, Medical University of Vienna (Austria); Weber, Michael [Department of Radiology, Medical University of Vienna (Austria)

    2010-10-15

    Purpose: To evaluate the prevalence of nephrogenic systemic fibrosis (NSF) in a patient population being at highest risk for developing this disease and to evaluate possible risk factors. Materials and methods: The radiological records of 552 patients with ESRD being on hemodialysis (HD) or peritoneal dialysis (PD) were retrospectively reviewed to identify whether the patients underwent MR-examinations with or without intravenous administration of GBCA. In case of exposure to GBCA, the number of contrast injections, the benchmark and the cumulative doses of GBCA, and possible cofactors regarding pathogenesis of NSF were recorded. Diagnosis of NSF was confirmed either by deep skin biopsy or by review of medical and histopathological records. Data of NSF patients were compared with data of dialysis patients who did not develop NSF after MR-examinations. Results: 146 dialysis patients underwent MRI without i.v.-administration of GBCA. No case of NSF was observed in this patient population. 195/552 patients proved to have a total number of 325 well-documented exposures to GBCA. Seven different types of GBCA were used during these MR-examinations. NSF prevalence rate was 1.6%. One patient died of NSF. Three different types of GBCA were involved in 6 NSF cases. 4/6 proved to be confounded cases. The cumulative dose of GBCA, history of thrombosis, recent surgery, and the combination of HD and PD proved to be significant cofactors for the development of NSF (p < .05). No significant difference regarding residual renal clearance (p = .898) and residual urine volume (p = .083) was found between NSF and non-NSF patients. Conclusion: The prevalence of NSF proved to be much lower in this high risk patient group being exposed to GBCA compared to the literature. NSF was not observed in ESRD patients undergoing MRI without administration of GBCA. Our data support a positive association between cumulative dose of GBCA and development of NSF. No positive association was found

  1. Effects of intravenous lipopolysaccharide administration on feed intake, ruminal forage degradability, and liquid parameters and physiological responses in beef cattle.

    Science.gov (United States)

    Lippolis, K D; Cooke, R F; Schubach, K M; Marques, R S; Bohnert, D W

    2017-07-01

    This experiment compared DMI, ruminal forage degradability, and liquid parameters as well as physiological responses in beef cattle receiving a lipopolysaccharide (LPS) challenge or not. Eight ruminally cannulated Angus × Hereford steers (485 ± 16 kg BW) were housed in individual pens on d -7, ranked by BW, and allocated to 1 of 2 treatments administered on d 0: 1) an intravenous (i.v.) bolus dose (0.5 μg/kg of BW, diluted in 5 mL of 0.9% sterile saline) of bacterial LPS ( 0111:B4) or 2) a 5-mL i.v. injection of 0.9% sterile saline (CON). Steers had free-choice access to mixed alfalfa-grass hay, water, and a commercial vitamin + mineral mix during the experiment (d -7 to 6). Hay DMI was evaluated daily from d -5 to 6. Immediately prior to treatment administration (h 0), polyester bags containing 4 g of ground dietary hay (DM basis) were immersed into the rumen of each steer and incubated for 0, 4, 8, 12, 24, 36, and 48 h for DM and NDF degradability evaluation. Steers were also intraruminally pulse-dosed with 5 g of Co-EDTA immediately prior to treatment administration, and rumen fluid samples were collected at 0, 2, 4, 6, 8, 12, 16, and 24 h for ruminal liquid volume and dilution rate calculations. Blood was collected every 2 h from -2 to 8 h, every 4 h from 8 to 16 h, every 12 h from 24 to 72 h, and every 24 h from 96 to 144 h relative to treatment administration. Values obtained before treatment administration were used as a covariate within each respective analysis. Steers receiving LPS had less ( ≤ 0.03) DMI on d 0 and 1 compared with CON steers. Steers receiving LPS had reduced ( ≤ 0.05) rumen liquid volume and dilution rate as well as ruminal disappearance rate and effective degradability of DM and NDF compared with CON steers. Steers receiving LPS had greater ( ≤ 0.05) plasma tumor necrosis factor α at 2 h, greater plasma haptoglobin from 24 to 72 h, greater plasma cortisol from 12 to 16 h, greater serum NEFA from 6 to 48 h, greater plasma insulin

  2. Lipid-Core Nanocapsules Act as a Drug Shuttle Through the Blood Brain Barrier and Reduce Glioblastoma After Intravenous or Oral Administration.

    Science.gov (United States)

    Rodrigues, Stephen F; Fiel, Luana A; Shimada, Ana L; Pereira, Natalia R; Guterres, Silvia S; Pohlmann, Adriana R; Farsky, Sandra H

    2016-05-01

    Lipid-core nanocapsules (LNC) are formed by an organogel surrounded by poly(epsilon-caprolactone) and stabilized by polysorbate 80. LNCs increase the concentration of drugs in the brain after oral or intravenous administration. We proposed to determine whether the drug is released from the LNC to cross the blood brain barrier (BBB) or the drug-loaded LNCs can cross the BBB to release the drug. We synthesized a Rhodamine B-polymer conjugate to prepare a fluorescent-labeled LNC formulation, and intravital microscopy was used to determine the ability of the LNCs to cross the brain barrier using different administration routes in C57BI/6 mice. A glioblastoma model was used to determine the impact of the LNC as a shuttle for treatment. After pial vessel exposure, intense fluorescence was detected inside the vessels 10 min after intravenous or 20 min after intraperitoneal injections of fluorescent-labeled LNC. The fluorescence was observed in the perivascular tissue after 30 and 60 min, respectively. Increased tissue fluorescence was detected 240 min after oral administration. The integrity of the barrier was determined during the experiments. Normal leukocyte and platelet adhesion to the vessel wall indicated that Rhodamine B-labeled LNC did not cause pial vessel alterations. After intravenous or oral administration, Rhodamine B-labeled LNC-containing co-encapsulated indomethacin and indomethacin ethyl ester exhibited similar behavior in pial vessels, being more efficient in the treatment of mice with glioblastoma than indomethacin in solution. Therefore, we demonstrated that LNCs act as drug shuttles through the BBB, delivering drugs in brain tissue with high efficiency and reducing glioblastoma after intravenous or oral administration.

  3. L-carnitine: effect of intravenous administration on fuel homeostasis in normal subjects and home-parenteral-nutrition patients with low plasma carnitine concentrations.

    Science.gov (United States)

    Bowyer, B A; Fleming, C R; Haymond, M W; Miles, J M

    1989-04-01

    We studied the effects of intravenous L-carnitine on the metabolism of fatty acids, ketone bodies, glucose, and branched-chain amino acids in four normal volunteers and four patients on long-term home parenteral nutrition (HPN) with low plasma carnitine concentrations. Substrate kinetics were determined by use of [1-14C]palmitate, [3,4-13C2]-acetoacetate, [6,6-2H2]glucose, and [5,5,5-2H3]leucine before and during a 3-h intravenous infusion of L-carnitine. HPN patients were restudied after 1 mo of nightly intravenous carnitine administration. HPN patients tolerated the short-term fast well, exhibiting neither hypoglycemia nor hypoketonemia. Intravenous carnitine had no effect on rates of fatty acid oxidation, ketone body production, glucose production, or leucine kinetics in either group. Routine addition of carnitine to the HPN regimen does not appear to be necessary. The failure of L-carnitine administration to have discernable effects on intermediary metabolism in normal volunteers casts doubt on its role in the treatment of a variety of medical conditions.

  4. Repeated post-exercise administration with a mixture of leucine and glucose alters the plasma amino acid profile in Standardbred trotters

    Directory of Open Access Journals (Sweden)

    Nostell Katarina EA

    2012-02-01

    Full Text Available Abstract Background The branched chain amino acid leucine is a potent stimulator of insulin secretion. Used in combination with glucose it can increase the insulin response and the post exercise re-synthesis of glycogen in man. Decreased plasma amino acid concentrations have been reported after intravenous or per oral administration of leucine in man as well as after a single per oral dose in horses. In man, a negative correlation between the insulin response and the concentrations of isoleucine, valine and methionine have been shown but results from horses are lacking. This study aims to determine the effect of repeated per oral administration with a mixture of glucose and leucine on the free amino acid profile and the insulin response in horses after glycogen-depleting exercise. Methods In a crossover design, after a glycogen depleting exercise, twelve Standardbred trotters received either repeated oral boluses of glucose, 1 g/kg body weight (BW at 0, 2 and 4 h with addition of leucine 0.1 g/kg BW at 0 and 4 h (GLU+LEU, or repeated boluses of water at 0, 2 and 4 h (CON. Blood samples for analysis of glucose, insulin and amino acid concentrations were collected prior to exercise and over a 6 h post-exercise period. A mixed model approach was used for the statistical analyses. Results Plasma leucine, isoleucine, valine, tyrosine and phenylalanine concentrations increased after exercise. Post-exercise serum glucose and plasma insulin response were significantly higher in the GLU+LEU treatment compared to the CON treatment. Plasma leucine concentrations increased after supplementation. During the post-exercise period isoleucine, valine and methionine concentrations decreased in both treatments but were significantly lower in the GLU+LEU treatment. There was no correlation between the insulin response and the response in plasma leucine, isoleucine, valine and methionine. Conclusions Repeated post-exercise administration with a mixture of leucine

  5. Integration of pharmacokinetic and pharmacodynamic indices of valnemulin in broiler chickens after a single intravenous and intramuscular administration.

    Science.gov (United States)

    Zhao, Dong-Hao; Zhou, Yu-Feng; Yu, Yang; Shi, Wei; Yang, Xue; Xiao, Xia; Deng, Hui; Qiao, Guilin Gary; Fang, Bing-Hu; Liu, Ya-Hong

    2014-07-01

    The antibacterial efficacy of valnemulin against Staphylococcus aureus was studied ex vivo in broiler chickens after intravenous and intramuscular administration at a dose of 10 mg/kg bodyweight (BW). The minimum inhibitory concentrations (MICs) of valnemulin against S. aureus strains ATCC 25923 in broth and serum were 0.12 and 1 µg/mL, respectively. The MIC50 and MIC90 of valnemulin against all susceptible S. aureus strains isolated from chickens in the test population were 0.06 and 0.12 μg/mL, respectively. Protein binding, which greatly influences the efficacy of valnemulin, was assayed by equilibrium dialysate in vitro. A high binding fraction of 86.2% was found, which seems in good agreement with the difference of bacterial susceptibility tests observed in broth and serum. The surrogate index of AUC0-24/MIC required for the lowest bacteriostatic effect, and 2 log10CFU reduction in bacterial count were 24.4 h and 38.0 h, respectively. The required daily dose of valnemulin for a bacteriostatic activity was calculated to be 15 mg/kg BW based on the MIC90 of 0.12 µg/mL. Considering the slow disposition process of valnemulin and an AUC0-24 h value of more than 10-fold obtained from diseased animals, a suggested dose of 3 mg/kg BW is sufficient to achieve a satisfactory therapeutic efficacy in infected broilers. Due to the time-dependent antibacterial characteristics of valnemulin, the recommended daily dose should be split into two or three sub-doses to achieve the highest effectiveness while diminishing the risk of development of bacterial resistance.

  6. Pharmacokinetics of bisphenol A in serum and adipose tissue following intravenous administration to adult female CD-1 mice.

    Science.gov (United States)

    Doerge, Daniel R; Twaddle, Nathan C; Vanlandingham, Michelle; Fisher, Jeffrey W

    2012-06-01

    Bisphenol A (BPA) is an important industrial chemical used as the monomer for polycarbonate plastic and in epoxy resins for use in food can liners. Worldwide biomonitoring studies consistently find high prevalence of BPA conjugates in urine consistent with pervasive exposure at levels typically below 1 μg/kg bw/day. The current study used LC/MS/MS to measure serum pharmacokinetics of unconjugated (active) and conjugated (inactive) BPA in adult female CD-1 mice following intravenous (IV) injection, which produces higher serum levels by circumventing the processes of absorption from the GI tract and presystemic metabolism that occur after oral administration. Deuterated BPA (100 μg/kg bw) was used to avoid interference by background contamination from trace amounts of native BPA. Additionally, the pharmacokinetics of unconjugated BPA were determined in adipose tissue, a proposed site of action and "depot" for BPA. After IV injection, unconjugated BPA rapidly distributed out of the circulation (t(1/2)=0.2 h) and terminal elimination also proceeded rapidly (t(1/2)=0.8 h). Consistent with the degree of aqueous solubility, lipid/water solubility ratio, and partitioning from blood into adipose tissue in vivo, the levels of unconjugated BPA in mouse adipose tissue rapidly reached a maximal level (0.25 h) that did not exceed the serum maximum at the initial sampling time (0.08 h). Terminal elimination of unconjugated BPA from adipose tissue (t(1/2)=7.0 h) was similar to that for conjugated BPA in serum (t(1/2)=6.6 h) and persistent nature of BPA, particularly when compared with slowly metabolized lipophilic organic pollutants like halogenated dibenzodioxins.

  7. Intravenous administration of glutathione protects parenchymal and non-parenchymal liver cells against reperfusion injury following rat liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Rolf J. Schauer; Sinan Kalmuk; Alexander L. Gerbes; Rosemarie Leiderer; Herbert Meissner; Friedrich W. Schildberg; Konrad Messmer; Manfred Bilzer

    2004-01-01

    AIM: To investigate the effects of intravenous administration of the antioxidant glutathione (GSH) on reperfusion injury following liver transplantation.METHODS: Livers of male Lewis rats were transplantedafter 24 h of hypothermic preservation in University of Wisconsin solution in a syngeneic setting. During a 2-h reperfusion period either saline (controls, n=8) or GSH administered via the jugular vein.RESULTS: Two hours after starting reperfusion plasma ALT increased to 1 457±281 U/L (mean±SE) in controls but to only 908±187 U/L (P<0.05) in animals treated with morphological findings on electron microscopy: GSH treatment prevented detachment of sinusoidal endothelial cells (SECs) as well as loss of microvilli and mitochondrial swelling of hepatooytes. Accordingly, postischemic bile flow increased 2-fold. Intravital fluorescence microscopy revealed a nearly complete restoration of sinusoidal blood flow and a significant reduction of leukocyte adherence to sinusoids and postsinusoidal venules. Following infusion of 50 μmol and and 97±18 mol/L, but to only 20±3 mol/L in untreated recipients. Furthermore, plasma glutathione disulfide (GSSG) increased untreated controls (1.8±0.5 mol/L vs 2.2±0.2 mol/L).CONCLUSION: Plasma GSH levels above a critical level may act as a "sink" for ROS produced in the hepatic vasculature during reperfusion of liver grafts. Therefore, GSH can be considered a candidate antioxidant for the prevention of reperfusion injury after liver transplantation, in particular since it has a low toxicity in humans.

  8. Pharmacokinetics of chloramphenicol following administration of intravenous and subcutaneous chloramphenicol sodium succinate, and subcutaneous chloramphenicol, to koalas (Phascolarctos cinereus).

    Science.gov (United States)

    Black, L A; McLachlan, A J; Griffith, J E; Higgins, D P; Gillett, A; Krockenberger, M B; Govendir, M

    2013-10-01

    Clinically normal koalas (n = 19) received a single dose of intravenous (i.v.) chloramphenicol sodium succinate (SS) (25 mg/kg; n = 6), subcutaneous (s.c.) chloramphenicol SS (60 mg/kg; n = 7) or s.c. chloramphenicol base (60 mg/kg; n = 6). Serial plasma samples were collected over 24-48 h, and chloramphenicol concentrations were determined using a validated high-performance liquid chromatography assay. The median (range) apparent clearance (CL/F) and elimination half-life (t(1/2)) of chloramphenicol after i.v. chloramphenicol SS administration were 0.52 (0.35-0.99) L/h/kg and 1.13 (0.76-1.40) h, respectively. Although the area under the concentration-time curve was comparable for the two s.c. formulations, the absorption rate-limited disposition of chloramphenicol base resulted in a lower median C(max) (2.52; range 0.75-6.80 μg/mL) and longer median tmax (8.00; range 4.00-12.00 h) than chloramphenicol SS (C(max) 20.37, range 13.88-25.15 μg/mL; t(max) 1.25, range 1.00-2.00 h). When these results were compared with susceptibility data for human Chlamydia isolates, the expected efficacy of the current chloramphenicol dosing regimen used in koalas to treat chlamydiosis remains uncertain and at odds with clinical observations. © 2012 John Wiley & Sons Ltd.

  9. Reduced Plasma Nonesterified Fatty Acid Levels and the Advent of an Acute Lung Injury in Mice after Intravenous or Enteral Oleic Acid Administration

    Directory of Open Access Journals (Sweden)

    Cassiano Felippe Gonçalves de Albuquerque

    2012-01-01

    Full Text Available Although exerting valuable functions in living organisms, nonesterified fatty acids (NEFAs can be toxic to cells. Increased blood concentration of oleic acid (OLA and other fatty acids is detected in many pathological conditions. In sepsis and leptospirosis, high plasma levels of NEFA and low albumin concentrations are correlated to the disease severity. Surprisingly, 24 h after intravenous or intragastric administration of OLA, main NEFA levels (OLA inclusive were dose dependently decreased. However, lung injury was detected in intravenously treated mice, and highest dose killed all mice. When administered by the enteral route, OLA was not toxic in any tested conditions. Results indicate that OLA has important regulatory properties on fatty acid metabolism, possibly lowering circulating fatty acid through activation of peroxisome proliferator-activated receptors. The significant reduction in blood NEFA levels detected after OLA enteral administration can contribute to the already known health benefits brought about by unsaturated-fatty-acid-enriched diets.

  10. The effects of repeated opioid administration on locomotor activity: II. Unidirectional cross-sensitization to cocaine.

    Science.gov (United States)

    Smith, Mark A; Greene-Naples, Jennifer L; Felder, Jennifer N; Iordanou, Jordan C; Lyle, Megan A; Walker, Katherine L

    2009-08-01

    Sensitization refers to an increase in sensitivity to the effects of a drug and is believed to play a role in the etiology of substance use disorders. Cross-sensitization has been observed between drugs from different pharmacological classes and may play a role in the escalation of drug use in polydrug-abusing populations. The purpose of this study was to examine cross-sensitization between opioids and cocaine and to determine the extent to which cross-sensitization is mediated by an opioid's selectivity for mu, kappa, and delta receptors. Separate groups of rats were treated with opioid receptor agonists and antagonists every other day for 10 days, and the locomotor effects of cocaine were tested 8 days later. The mu agonists, morphine and buprenorphine, and the delta agonist, BW373U86 [(+/-)-4-[(R(*))-[(2S(*),5R(*))-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-hydroxyphenyl)methyl]-N,N-diethylbenzamide hydrochloride], produced cross-sensitization to cocaine, such that repeated administration of these drugs over a 10-day period significantly enhanced cocaine's locomotor effects when tested later. Coadministration of the opioid antagonist naltrexone prevented morphine and buprenorphine from producing cross-sensitization. Coadministration of naltrexone, but not the delta antagonist naltrindole, also prevented BW373U86 from producing cross-sensitization. The kappa agonist spiradoline failed to produce cross-sensitization, but coadministration of spiradoline prevented morphine and buprenorphine from producing cross-sensitization. The ability of spiradoline to block cross-sensitization was itself blocked by the kappa antagonist nor-binaltorphimine. The mixed mu/kappa opioids butorphanol, nalbuphine, and nalorphine did not produce cross-sensitization under any condition examined. These data indicate that agonist activity at mu receptors positively modulates cross-sensitization between opioids and cocaine, whereas agonist activity at kappa receptors negatively modulates

  11. Clinical Informatics: Recursive Concurrence Intravenous Medication Administration Systems Protocols for Addressing the Potential Problem of Recessive Lethal Autonomy in Smart Infusion Systems

    OpenAIRE

    Nyagudi, Nyagudi Musandu

    2016-01-01

    Smart Infusion Pumps are vital tools for use in administering a broad range of parenteral/intravenous medications. Safe and effective use of smart infusion pumps depends upon their integration with Pump Servers, Computerized Physician Order Entry Systems, Pharmacy Information Systems, DERS/MERS Dose/Medication Error Reduction Systems( and the digital Drug Libraries that they use), eMARS/electronic Medication Administration Records Systems, etc. More computer systems result in more computer ne...

  12. Pharmacokinetics of plasma-derived C1-esterase inhibitor after subcutaneous versus intravenous administration in subjects with mild or moderate hereditary angioedema: the PASSION study

    OpenAIRE

    Martinez-Saguer, Inmaculada; Cicardi, Marco; Suffritti, Chiara; Rusicke, Eva; Aygören-Pürsün, Emel; Stoll, Hildegard; Rossmanith, Tanja; Feussner, Annette; Kalina, Uwe; Kreuz, Wolfhart

    2013-01-01

    Background Hereditary angioedema (HAE) is a rare disease caused by C1-esterase inhibitor (C1-INH) deficiency, characterized by periodic attacks of acute edema affecting subcutaneous (SC) tissues and mucous membranes. Human C1-INH concentrate given intravenously (IV) is effective and safe, but venous access may be difficult. We compared SC and IV administration of human pasteurized C1-INH concentrate with respect to pharmacokinetics, pharmacodynamics, and safety. Study Design and Methods This ...

  13. METHYLPHENIDATE ENHANCES THE ABUSE-RELATED BEHAVIORAL EFFECTS OF NICOTINE IN RATS: INTRAVENOUS SELF-ADMINISTRATION, DRUG DISCRIMINATION AND LOCOMOTOR CROSS-SENSITIZATION

    OpenAIRE

    Wooters, Thomas E.; Neugebauer, Nichole M.; Rush, Craig R.; Bardo, Michael T.

    2007-01-01

    Stimulant drugs, including d-amphetamine, cocaine and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination and locomotor cross-se...

  14. The assesment of effectiveness of plasmonic resonance photothermal therapy in tumor-bearing rats after multiple intravenous administration of gold nanorods

    Science.gov (United States)

    Bucharskaya, Alla B.; Maslyakova, Galina N.; Navolokin, Nikita A.; Terentyuk, Georgy S.; Khlebtsov, Boris N.; Khlebtsov, Nikolai G.; Bashkatov, Alexey N.; Genina, Elina A.; Tuchin, V. V.

    2017-03-01

    To assess the effectiveness of plasmonic photothermal therapy (PPT) multiple intravenous strategy of gold nanorods (GNRs) administration was used before laser exposure. The model of alveolar liver cancer PC-1 was used in male outbred albino rats, which were intravenously administrated by single and multiple injections of GNRs and then were treated by PPT. The gold dosage was 400 μg (single injection group), 800 μg (double injection group), 1200 μg (triple injection group), and absorption maximum of gold nanorods suspension was at the wavelength of 808 nm. 24 hours after last injection the tumors were irradiated by the 808-nm diode laser during 15 min at power density 2.3 W/cm2. Temperature control of the tumor heating was provided by IR imager. 24 hours after the PPT the half of animals from each group was withdrawn from the experiments and the sampling tumor tissue for morphological study was performed. In survived animals the growth of tumors was evaluated during 21 days after the PPT. The antitumor effects of PPT after triple intravenous injection were comparable with those obtained at direct intratumoral administration of similar total dose of GNRs. The effectiveness of PPT depended on gold accumulation in tumor, probably, due to sufficient vascularization of tumor tissue.

  15. Gr-1+CD11b+ myeloid cells efficiently home to site of injury after intravenous administration and enhance diabetic wound healing by neoangiogenesis.

    Science.gov (United States)

    Tong, Xiaozhe; Lv, Gang; Huang, Jianhua; Min, Yongfen; Yang, Li; Lin, Pengnian Charles

    2014-06-01

    Vascularization is an important factor that affects diabetic wound healing. There is increasing evidence that myeloid cell lineages play a role in neovascularization. In this study, the efficiency of Gr-1+CD11b+ myeloid cells to home to the site of injury and enhance diabetic wound healing by neoangiogenesis after intravenous administration was investigated. Gr-1+CD11b+ myeloid cells were injected into tail vein after establishment of dorsal window chamber, hindlimb ischaemia and ear-punch injury in diabetic or non-diabetic mice. The Gr-1+CD11b+ myeloid cells efficiently homed to the site of injury after intravenous administration and increased neoangiogenesis. The chemokine receptor type 4 (CXCR4) is robustly expressed by Gr-1+CD11b+ myeloid cells. Inhibition of CXCR4 decreases the homing ability of Gr-1+CD11b+ myeloid cells to the site of injury, which indicates that the CXCR4/SDF-1 axis plays an important role in the homing of Gr-1+CD11b+ myeloid cells to the site of injury. In addition, Gr-1+CD11b+ myeloid cells were found to improve blood flow recovery of ischaemic limb and enhance wound healing in diabetic mice by neoangiogenesis after intravenous administration. Taken together, the results of this study suggest that Gr-1+CD11b+ myeloid cells may serve as a potential cell therapy for diabetic wound healing.

  16. Repeated oral administration of chitosan/DNA nanoparticles delivers functional FVIII with the absence of antibodies in hemophilia A mice.

    Science.gov (United States)

    Dhadwar, S S; Kiernan, J; Wen, J; Hortelano, G

    2010-12-01

    Current treatment of hemophilia A is expensive and involves regular infusions of factor (F)VIII concentrates. The supply of functional FVIII is further compromised by the generation of neutralizing antibodies. Thus, the development of an alternative safe, cost effective, non-invasive treatment that circumvents immune response induction is desirable. To evaluate the feasibility of oral administration of chitosan nanoparticles containing FVIII DNA to provide sustainable FVIII activity in hemophilia A mice. Nanoparticles were characterized for morphology, DNA protection and transfection efficiency. Oral administration of nanoparticles containing canine FVIII in C57Bl/6 FVIII(-/-) hemophilia A mice was evaluated for biodistribution, plasma FVIII activity and phenotypic correction. Sustainable FVIII expression was elucidated after repeated nanoparticle administration. Immune responses to repeated oral nanoparticle administration were also investigated. Chitosan nanoparticles had a particle size range of 200-400 nm and protected DNA from endonuclease and pH degradation. In addition, nanoparticles transfected HEK 293 cells resulted in expression of eGFP, luciferase and FVIII. Hemophilia A mice that ingested chitosan nanoparticles demonstrated transient canine FVIII expression reaching > 100 mU 1 day after treatment, together with partial phenotypic correction. The delivered FVIII plasmid DNA was detected in the intestine and, to a lesser extent, in the liver. Importantly, repeated weekly administrations restored FVIII activity. Furthermore, inhibitors and non-neutralizing FVIII antibodies were not detectable. Repeat oral administration of FVIII DNA formulated in chitosan nanoparticles resulted in sustained FVIII activity in hemophilic mice, and thus may provide a non-invasive alternative treatment for hemophilia A. © 2010 International Society on Thrombosis and Haemostasis.

  17. Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration.

    Science.gov (United States)

    Kenward, Hannah; Pelligand, Ludovic; Elliott, Jonathan

    2014-08-01

    Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies.

  18. The Optimal Route of Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Abciximab During Percutaneous Coronary Intervention; Intravenous Versus Intracoronary

    DEFF Research Database (Denmark)

    Iversen, Allan; Galatius, Søren; Jensen, Jan S

    2008-01-01

    -randomised and retrospective studies or studies with short follow-up. No definite conclusion can be made based on these studies.In this review we present the current knowledge published about the intracoronary administration of Abciximab including the mechanisms behind the potential beneficial effects, and the safety...... and thrombus formation, but other mechanisms, such as suppression of the inflammatory pathways, have also been proposed to contribute to the benefits of Abciximab.The optimal route of administration, i.e. intravenous versus intracoronary, of the first dose has been questioned, but only tested in small, non...

  19. Targeted Intra-arterial Transplantation of Stem Cells to the Injured CNS is More Effective than Intravenous Administration - Engraftment is Dependent on Cell Type and Adhesion Molecule Expression

    DEFF Research Database (Denmark)

    Lundberg, Johan; Södersten, Erik; Sundström, Erik

    2011-01-01

    Stem cell transplantation procedures using intraparenchymal injections cause tissue injury in addition to associated surgical risks. Intra-venous cell administration give engraftment in parenchymal lesions although the method has low efficacy and specificity. In pathological conditions...... with inflammation, such as traumatic brain injury, there is a transient up-regulation of ICAM-1 and VCAM-1 which might provide enviromental cues for migration of stem cells from blood to parenchyma. The aim of this study was to i) analyze the effect of intra-arterial administration on cellular engraftment, ii......) compare engraftment and side effects between three different stem cell systems and iii) analyze gene expression in these three systems....

  20. Impact of repeated intravenous bone marrow mesenchymal stem cells infusion on myocardial collagen network remodeling in a rat model of doxorubicin-induced dilated cardiomyopathy.

    Science.gov (United States)

    Yu, Qin; Li, Qianxiao; Na, Rongmei; Li, Xiaofei; Liu, Baiting; Meng, Lili; Liutong, Hanyu; Fang, Weiyi; Zhu, Ning; Zheng, Xiaoqun

    2014-02-01

    Bone marrow mesenchymal stem cells (MSCs) transplantation improved cardiac function and reduced myocardial fibrosis in both ischemic and non-ischemic cardiomyopathies. We evaluated the effects of repeated peripheral vein injection of MSCs on collagen network remodeling and myocardial TGF-β1, AT1, CYP11B2 (aldosterone synthase) gene expressions in a rat model of doxorubicin (DOX)-induced dilated cardiomyopathy (DCM). Thirty-eight out of 53 SD rats survived at 10 weeks post-DOX injection (2.5 mg/kg/week for 6 weeks, i.p.) were divided into DCM blank (without treatment, n = 12), DCM placebo (intravenous tail injection of 0.5 mL serum-free culture medium every other day for ten times, n = 13), and DCM plus MSCs group (intravenous tail injection of 5 × 10(6) MSCs dissolved in 0.5 mL serum-free culture medium every other day for 10 times, n = 13). Ten untreated rats served as normal controls. At 20 weeks after DOX injection, echocardiography, myocardial collagen content, myocardial expressions of types I and III collagen, TGF-β1, AT1, and CYP11B2 were compared among groups. At 20 weeks post-DOX injection, 8 rats (67%) survived in DCM blank group, 9 rats (69%) survived in DCM placebo group while 13 rats (100 %) survived in DCM plus MSCs group. Left ventricular end-diastolic diameter was significantly higher and ejection fraction was significantly lower in DCM blank and DCM placebo groups compared to normal control rats, which were significantly improved in DCM plus MSCs group (all p collagen volume fraction, types I and III collagen, myocardial mRNA expressions of TGF-β1, AT1, CYP11B2, and collagen I/III ratio were all significantly lower in DCM plus MSCs group compared to DCM blank and DCM placebo groups (all p collagen network remodeling possibly through downregulating renin-angiotensin-aldosterone system in DOX-induced DCM rats.

  1. Intravenous Contrast Medium Administration for Computed Tomography Scan in Emergency: A Possible Cause of Contrast-Induced Nephropathy

    Directory of Open Access Journals (Sweden)

    Lantam Sonhaye

    2015-01-01

    Full Text Available The goal of this study was to assess risk for CIN after CT Scan during an emergency and to identify risk factors for the patient. Prospective review of all patients admitted to the emergency room (ER of the Teaching Hospital of Lomé (Togo during a 2-year period. CIN was defined as an increase in serum creatinine by 0.5 mg/dL from admission after undergoing CT Scan with intravenous contrast. A total of 620 patients underwent a CT Scan in the emergency room using intravenous contrast and 672 patients took the CT Scan without intravenous contrast. Out of the patients who received intravenous contrast for CT Scan, three percent of them developed CIN during their admission. Moreover, upon discharge no patient had continued renal impairment. No patient required dialysis during their admission. The multivariate analysis of all patients who had serial creatinine levels (including those who did not receive any contrast load shows no increased risk for acute kidney injury associated intravenous contrast (odds ratio = 0.619, p value = 0.886; only diabetes remains independent risk factor of acute kidney injury (odds ratio = 6.26, p value = 0.031.

  2. Comparative pharmacokinetics and bile transformation of R-enantiomer and racemic bambuterol after single-dose intravenous, oral administration in rats and beagle dogs.

    Science.gov (United States)

    Guan, Su; Hu, Chun-Yun; He, Meng-Ying; Yang, Ying-Ying; Tang, Yu-Xin; Chen, Jie-di; Huang, Li-Jie; Tan, Wen

    2015-12-01

    This study was to compare pharmacokinetics and bile transformation of R-enantiomer bambuterol with its racemate. Pharmacokinetics of R-enantiomer was investigated after single-dose intravenous and three doses of oral administration to rats and beagle dogs. To compare the pharmacokinetics with racemic bambuterol, the same oral doses of racemic bambuterol were also administrated; the blood and bile samples were collected by cannulation. A validated LC-MS/MS method was used to assess the level of bambuterol in plasma and bile. After single intravenous administration, no significant differences were observed between the two drugs in pharmacokinetic data. After oral dosing of R-bambuterol, the AUCs of R-enantiomer presented linear correlation. After same oral dosing of R-enantiomer and its racemate, all the pharmacokinetic parameters were equivalent. However, the clearance and apparent distribution had different results due to species and administration route difference. The bile transformation of these two compounds was similar and implicated that liver transformation accounted for the major metabolism of them. The bioavailability of R-enantiomer and racemate were comparative and relatively high in beagle dogs. Thus, R-enantiomer had a comparative pharmacokinetic profile and bile transformation with racemic bambuterol in rats and beagle dogs. These findings provided references for further clinical study.

  3. Repeated administration of D-amphetamine induces loss of [{sup 123}I]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study

    Energy Technology Data Exchange (ETDEWEB)

    Booij, Jan [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands)]. E-mail: j.booij@amc.uva.nl; Bruin, Kora de [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands); Gunning, W. Boudewijn [Department of Neurology, Epilepsy Centre Kempenhaeghe, 5590 AB Heeze (Netherlands)

    2006-04-15

    In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in amphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of D-AMPH or methamphetamine (METH) may induce loss of binding to striatal DATs in rats by using an experimental biodistribution study design and a SPECT tracer for the DAT ([{sup 123}I]FP-CIT). Methods: Groups of male rats (n=10 per group) were treated with D-AMPH (10 mg/kg body weight), METH (10 mg/kg body weight), or saline, twice a day for 5 consecutive days. Five days later, [{sup 123}I]FP-CIT was injected intravenously, and 2 h later, the rats were sacrificed and radioactivity was assayed. Results: In D-AMPH but not METH-treated rats, striatal [{sup 123}I]FP-CIT uptake was significantly lower (approximately 17%) than in the control group. Conclusion: These data show that [{sup 123}I]FP-CIT can be used to detect AMPH-induced changes in DAT binding and may validate the use of DAT radiotracers to study AMPH-induced changes in striatal DAT binding in vivo.

  4. Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice.

    Directory of Open Access Journals (Sweden)

    Paul W Denton

    Full Text Available Successful antiretroviral pre-exposure prophylaxis (PrEP for mucosal and intravenous HIV-1 transmission could reduce new infections among targeted high-risk populations including discordant couples, injection drug users, high-risk women and men who have sex with men. Targeted antiretroviral PrEP could be particularly effective at slowing the spread of HIV-1 if a single antiretroviral combination were found to be broadly protective across multiple routes of transmission. Therefore, we designed our in vivo preclinical study to systematically investigate whether rectal and intravenous HIV-1 transmission can be blocked by antiretrovirals administered systemically prior to HIV-1 exposure. We performed these studies using a highly relevant in vivo model of mucosal HIV-1 transmission, humanized Bone marrow/Liver/Thymus mice (BLT. BLT mice are susceptible to HIV-1 infection via three major physiological routes of viral transmission: vaginal, rectal and intravenous. Our results show that BLT mice given systemic antiretroviral PrEP are efficiently protected from HIV-1 infection regardless of the route of exposure. Specifically, systemic antiretroviral PrEP with emtricitabine and tenofovir disoproxil fumarate prevented both rectal (Chi square = 8.6, df = 1, p = 0.003 and intravenous (Chi square = 13, df = 1, p = 0.0003 HIV-1 transmission. Our results indicate that antiretroviral PrEP has the potential to be broadly effective at preventing new rectal or intravenous HIV transmissions in targeted high risk individuals. These in vivo preclinical findings provide strong experimental evidence supporting the potential clinical implementation of antiretroviral based pre-exposure prophylactic measures to prevent the spread of HIV/AIDS.

  5. Short-term repeated corticosterone administration enhances glutamatergic but not GABAergic transmission in the rat motor cortex.

    Science.gov (United States)

    Kula, Joanna; Blasiak, Anna; Czerw, Anna; Tylko, Grzegorz; Sowa, Joanna; Hess, Grzegorz

    2016-04-01

    It has been demonstrated that stress impairs performance of skilled reaching and walking tasks in rats due to the action of glucocorticoids involved in the stress response. Skilled reaching and walking are controlled by the primary motor cortex (M1); however, it is not known whether stress-related impairments in skilled motor tasks are related to functional and/or structural alterations within the M1. We studied the effects of single and repeated injections of corticosterone (twice daily for 7 days) on spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) recorded from layer II/III pyramidal neurons in ex vivo slices of the M1, prepared 2 days after the last administration of the hormone. We also measured the density of dendritic spines on pyramidal cells and the protein levels of selected subunits of AMPA, NMDA, and GABAA receptors after repeated corticosterone administration. Repeatedly administered corticosterone induced an increase in the frequency but not in the amplitude of sEPSCs, while a single administration had no effect on the recorded excitatory currents. The frequency and amplitude of sIPSCs as well as the excitability of pyramidal cells were changed neither after single nor after repeated corticosterone administration. Treatment with corticosterone for 7 days did not modify the density of dendritic spines on pyramidal neurons. Corticosterone influenced neither the protein levels of GluA1, GluA2, GluN1, GluN2A, and GluN2B subunits of glutamate receptors nor those of α1, β2, and γ2 subunits of the GABAA receptor. The increase in sEPSCs frequency induced by repeated corticosterone administration faded out within 7 days. These data indicate that prolonged administration of exogenous corticosterone selectively and reversibly enhances glutamatergic, but not GABAergic transmission in the rat motor cortex. Our results suggest that corticosterone treatment results in an enhancement of spontaneous glutamate release from presynaptic

  6. Intravenous Administration Is an Effective and Safe Route for Cancer Gene Therapy Using the Bifidobacterium-Mediated Recombinant HSV-1 Thymidine Kinase and Ganciclovir

    Directory of Open Access Journals (Sweden)

    Huicong Zhou

    2016-06-01

    Full Text Available The herpes simplex virus thymidine kinase/ganciclovir (HSV TK/GCV system is one of the best studied cancer suicide gene therapy systems. Our previous study showed that caspase 3 expression was upregulated and bladder tumor growth was significantly reduced in rats treated with a combination of Bifidobacterium (BF and HSV TK/GCV (BF-rTK/GCV. However, it was raised whether the BF-mediated recombinant thymidine kinase combined with ganciclovir (BF-rTK/GCV was safe to administer via venous for cancer gene therapy. To answer this question, the antitumor effects of BF-rTK/GCV were mainly evaluated in a xenograft nude mouse model bearing MKN-45 gastric tumor cells. The immune response, including analysis of cytokine profiles, was analyzed to evaluate the safety of intramuscular and intravenous injection of BF-rTK in BALB/c mice. The results suggested that gastric tumor growth was significantly inhibited in vivo by BF-rTK/GCV. However, the BF-rTK/GCV had no effect on mouse body weight, indicating that the treatment was safe for the host. The results of cytokine profile analysis indicated that intravenous injection of a low dose of BF-rTK resulted in a weaker cytokine response than that obtained with intramuscular injection. Furthermore, immunohistochemical analysis showed that intravenous administration did not affect the expression of immune-associated TLR2 and TLR4. Finally, the BF-rTK/GCV inhibited vascular endothelial growth factor (VEGF expression in mouse model, which is helpful for inhibiting of tumor angiogenesis. That meant intravenous administration of BF-rTK/GCV was an effective and safe way for cancer gene therapy.

  7. Pharmacokinetics of Repeated Melatonin Drug Administrations Prior to and After Surgery

    DEFF Research Database (Denmark)

    Harpsøe, Nathja Groth; Andersen, Lars Peter Kloster; Mielke, Louise Vennegaard

    2016-01-01

    treatment protocol was standardized between patients. During the study, each patient received two separate oral administrations of melatonin 10 mg. Melatonin was administered 60 min before surgery, and at 9:00 p.m. the evening after surgery. The pharmacokinetic variables absorption half-life (t ½ absorption...... not differ between the study phases (p > 0.05). CONCLUSIONS: These preliminary results indicate that postoperative melatonin dose should be augmented compared with preoperative administration if corresponding melatonin plasma levels are intended. Furthermore, postoperative administration times should...... be advanced compared with preoperative administration....

  8. Effect of Intravenous Administration Center on Improving the Quality of Intravenous Drug Use%静脉用药调配中心对提高静脉用药质量的作用分析

    Institute of Scientific and Technical Information of China (English)

    曾杰

    2015-01-01

    目的 探讨静脉用药调配中心对提高静脉用药质量的作用. 方法 该院静脉用药调配中心2010年12月开始投入使用.静脉用药调配中心成立前为对照组,静脉用药调配中心成立后为观察组,统计分析医院抽检的静脉用药差错率. 并统计分析两组患者对静脉输液的满意度. 结果 两组各抽检所配的4000袋药品中,对照组发现错误578袋,差错率14.45%;观察组发现错误126袋,差错率3.15%. 观察组的差错发生率明显低于对照组,差异具有统计学意义(P<0.05).观察组对静脉输液的满意度为98%明显高于对照组的85%,差异也具有统计学意义(P<0.05).结论 静脉用药调配中心建立的配药模式有效的保证了临床医疗、护理以及药学的结合,从而达到科学、合理、安全用药的目的.%Objective To investigate the effect of intravenous administration center on improving the quality of intravenous drug use. Methods The center of intravenous drug use in our hospital began to put into use in December 2010. In the con-trol group, after the establishment of the center for intravenous drug use, for the observation group, the statistical analysis of the hospital sampling of the intravenous drug use error rate. The satisfaction of the two groups of patients with venous transfusion was analyzed. Results In the two groups, the control group was found to have an error of 578 bags, the error rate was 14.45, and the observation group was 126 bags, the error rate was 3.15. The observation group was significantly lower than that of the control group, the difference was statistically significant (P<0.05). The satisfaction of the observation group for intravenous infusion was 85, significantly higher than the control group of 98, the difference was statistically significant (P<0.05). Conclusion Intravenous drug allocation center established dispensing mode effectively ensures the clinical medi-cal treatment, nursing and pharmacy binding, so

  9. No significant effects of single intravenous, single oral and subchronic oral administration of acetylcholinesterase inhibitors on striatal [{sup 123}I]FP-CIT binding in rats

    Energy Technology Data Exchange (ETDEWEB)

    Knol, R.J.J.; Booij, J. [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands); Graduate School of Neurosciences, Amsterdam (Netherlands); Bruin, K. de; Eck-Smit, B.L.F. van [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands)

    2008-03-15

    [{sup 123}I]FP-CIT SPECT is a valuable diagnostic tool to discriminate Lewy body dementia from Alzheimer's dementia. To date, however, it is uncertain whether the frequently used acetylcholinesterase inhibitors (AChEIs) by demented patients, have an effect on [{sup 123}I]FP-CIT binding to dopamine transporters (DATs). Earlier animal studies showed a decline of DAT availability after acute intravenous injection of AChEIs. The aim of this study was to investigate effects of single intravenous, single oral and subchronic oral administration of AChEIs on DAT availability in the rat brain as measured by [{sup 123}I]FP-CIT. Biodistribution studies were performed in Wistar rats (n = 5-16 per group). Before [{sup 123}I]FP-CIT injection, rats were injected intravenously with a single dose of the AChEI rivastigmine (2.5 mg/kg body weight) or donepezil (0.5 mg/kg), the DAT-blocker methylphenidate (10 mg/kg) or saline. A second group was orally treated with a single dose of rivastigmine or donepezil (2.5 mg/kg), methylphenidate (10 mg/kg) or saline before injection of [{sup 123}I]FP-CIT. Studies were also performed in rats that were orally treated during 14 consecutive days with either rivastigmine (1 mg/kg daily), donepezil (1.5 mg/kg daily), methylphenidate (2.5 mg/kg) or saline. Brain parts were assayed in a gamma counter, and specific striatum/cerebellum ratios were calculated for the [{sup 123}I]FP-CIT binding to DATs. No significant effects of either single intravenous, single oral or subchronic oral administration of AChEIs on striatal FP-CIT binding could be detected. Single pretreatment with methylphenidate resulted in an expected significantly lower striatal FP-CIT binding. We conclude that in rats, single intravenous and single or subchronic oral administration of the tested AChEIs does not lead to an important alteration of [{sup 123}I]FP-CIT binding to striatal DATs. Therefore, it is unlikely that these drugs will induce large effects on the interpretation of

  10. The delayed lung responses to single and repeated intratracheal administration of pure cobalt and hard metal powder in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Lasfargues, G.; Lardot, C.; Lauwerys, R.; Lison, D. [Catholic Univ. of Louvain (Belgium)] [and others

    1995-05-01

    Epidemiological and clinical studies suggest that inhalation of cobalt metal dust (Co) mixed with tungsten carbide particles (WC), but not of cobalt dust alone, may cause interstitial pulmonary lesions (hard metal disease). In previous studies in the rat, we have demonstrated the greater acute pulmonary toxicity of a WC-Co mixture was greater compared to Co or WC alone. The present study compares the delayed lung response after intratracheal administration of Co or WC-Co particles. The responses were also compared with those obtained after treatment with arsenic trioxide and crystalline silica used as reference materials producing an acute toxic insult and progressive fibrogenic response, respectively. Cellular and biochemical parameters were measured in bronchoalveolar lavage fluid following single and repeated intratracheal instillations. The results indicate the delayed lung response observed after WC-Co is different from that after cobalt metal alone. A single intratracheal dose of WC-Co (1, 5, or 10 mg/100 g body wt) induced an acute alveolitis which persisted for at least 1 month. Four months after a single instillation of WC-Co, no clear histological lung fibrosis could however be evidenced, indicating a reversibility of the lesions. The effects of cobalt (0.06, 0.3, or 0.6 mg/100 g body wt) were very modest, if any. Following repeated intratracheal instillations, increased lung hydroxyproline content and histopathological evidence of interstitial fibrosis were observed after WC-Co (4x1 mg/100 g body wt), but not after administration of each component separately, i.e., Co (4x0.06 mg/100 g body wt) or WC (4x1 mg/100 g body wt). The mechanism of the fibrotic reaction induced by WC-Co seems different from the progressive inflammatory reaction induced by crystalline silica. We suggest that it might result from a scarring reaction elicited by repeated acute insults as observed after repeated administration of arsenic trioxide. 34 refs., 10 figs., 3 tabs.

  11. Pharmacokinetics, protein binding and metabolic profile of 3H-icometasone enbutate following intravenous, oral and intratracheal administrations to Sprague-Dawley rats.

    Science.gov (United States)

    Duchêne, P; Giudicelli, M D; Neau, B; Gronfier, A; Firmin, Y; Villax, P; Saivin, S; Houin, G

    1998-04-01

    Absorption, distribution and excretion of 3H-icometasone enbutate (9 alpha-chloro-11 beta,17 alpha,21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione, 17-butyrate, 21-acetate, CAS 103466-73-5 CL09) were studied in male and female Sprague-Dawley rats after a single dose administration by intravenous (1 mg/kg), oral and intratracheal (2 mg/kg) routes. The metabolic profile after the different routes and protein binding were also determined. Independent of the route, the radioactivity was mainly excreted in faeces. Less than 10% of the dose were excreted in urine. The majority of the administered doses was recovered within 24 h postdose, and the total recovery of the doses administered was obtained. After oral and intravenous administration to bile-duct cannulated rats, most of the radioactivity was excreted in the bile (80% of the administered dose) and some radioactivity was found in the faeces. It can thus be concluded that some intestinal secretion occurred. After oral administration, mean maximum blood concentrations were obtained about 0.75 h postdose. For the intratracheal route, the radioactive dose administered was too low to determine precise blood pharmacokinetic parameters. However, the distribution study results allowed us to conclude that the drug was absorbed first from the lungs and then from the gastrointestinal tract. Immediately after the intravenous injection, the liver, the kidneys, the small intestine and its contents and the carcass presented the highest levels of radioactivity. 168 h postdose, low radioactivity was still measurable in these organs. In other tissues, the radioactivity decreased reaching the limit of quantification 72 h postdose. After oral administration, the maximum concentrations were observed 1 h after administration in the liver, the small intestine and its contents. Then the radioactivity decreased in most of the tissues but a slight increase at 72 and/or 120 h postdose was noted in large intestine contents, carcass

  12. Comparison of the Intraperitoneal, Retroorbital and per Oral Routes for F-18 FDG Administration as Effective Alternatives to Intravenous Administration in Mouse Tumor Models Using Small Animal PET/CT Studies.

    Science.gov (United States)

    Kim, Chulhan; Kim, In Hye; Kim, Seo-Il; Kim, Young Sang; Kang, Se Hun; Moon, Seung Hwan; Kim, Tae-Sung; Kim, Seok-Ki

    2011-09-01

    We compared alternative routes for (18)F-fluorodeoxyglucose (FDG) administration, such as the retroorbital (RO), intraperitoneal (IP) and per oral (PO) routes, with the intravenous (IV) route in normal tissues and tumors of mice. CRL-1642 (ATCC, Lewis lung carcinoma) cells were inoculated in female BALB/c-nu/nu mice 6 to 10 weeks old. When the tumor grew to about 9 mm in diameter, positron emission tomography (PET) scans were performed after FDG administration via the RO, IP, PO or IV route. Additional serial PET scans were performed using the RO, IV or IP route alternatively from 5 to 29 days after the tumor cell injection. There was no significant difference in the FDG uptake in normal tissues at 60 min after FDG administration via RO, IP and IV routes. PO administration, however, showed delayed distribution and unwanted high gastrointestinal uptake. Tumoral uptake of FDG showed a similar temporal pattern and increased until 60 min after FDG administration in the RO, IP and IV injection groups. In the PO administration group, tumoral uptake was delayed and reduced. There was no statistical difference among the RO, IP and IV administration groups for additional serial PET scans. RO administration is an effective alternative route to IV administration for mouse FDG PET scans using normal mice and tumor models. In addition, IP administration can be a practical alternative in the late phase, although the initial uptake is lower than those in the IV and RO groups.

  13. Safety and feasibility of countering neurological impairment by intravenous administration of autologous cord blood in cerebral palsy

    Directory of Open Access Journals (Sweden)

    Lee Young-Ho

    2012-03-01

    Full Text Available Abstract Backgrounds We conducted a pilot study of the infusion of intravenous autologous cord blood (CB in children with cerebral palsy (CP to assess the safety and feasibility of the procedure as well as its potential efficacy in countering neurological impairment. Methods Patients diagnosed with CP were enrolled in this study if their parents had elected to bank their CB at birth. Cryopreserved CB units were thawed and infused intravenously over 10~20 minutes. We assessed potential efficacy over 6 months by brain magnetic resonance imaging (MRI-diffusion tensor imaging (DTI, brain perfusion single-photon emission computed tomography (SPECT, and various evaluation tools for motor and cognitive functions. Results Twenty patients received autologous CB infusion and were evaluated. The types of CP were as follows: 11 quadriplegics, 6 hemiplegics, and 3 diplegics. Infusion was generally well-tolerated, although 5 patients experienced temporary nausea, hemoglobinuria, or urticaria during intravenous infusion. Diverse neurological domains improved in 5 patients (25% as assessed with developmental evaluation tools as well as by fractional anisotropy values in brain MRI-DTI. The neurologic improvement occurred significantly in patients with diplegia or hemiplegia rather than quadriplegia. Conclusions Autologous CB infusion is safe and feasible, and has yielded potential benefits in children with CP.

  14. Administration of paracetamol versus dipyrone by intravenous patient-controlled analgesia for postoperative pain relief in children after tonsillectomy

    Directory of Open Access Journals (Sweden)

    Mesut Sener

    2015-12-01

    Full Text Available BACKGROUND AND OBJECTIVE: We compared the efficacy of intravenous (IV paracetamol versus dipyrone via patient-controlled analgesia (PCA for postoperative pain relief in children. METHODS: The study was composed of 120 children who had undergone elective tonsillectomy after receiving general anesthesia. Patients were divided into 3 groups according to the dosage of postoperative intravenous-patient-controlled analgesia: paracetamol, dipyrone, or placebo. Pain was evaluated using a 0- to 100-mm visual analog scale and 1- to 4-pain relief score at 30 min, 1, 2, 4, 6, 12, and 24 h postoperatively. Pethidine (0.25 mg kg-1 was administered intravenously to patients requiring rescue analgesia. Pethidine requirements were recorded during the first 24 h postoperatively, and treatment related adverse effects were noted. RESULTS: Postoperative visual analog scale scores were significantly lower with paracetamol group compared with placebo group at 6 h (p 0.05. Postoperative pethidine requirements were significantly lower with paracetamol and dipyrone groups compared with placebo group (62.5%, 68.4% vs 90%, p 0.05. CONCLUSIONS: Paracetamol and dipyrone have well tolerability profile and effective analgesic properties when administered IV-PCA for postoperative analgesia in children after tonsillectomy.

  15. Biodistribution of BPA and BSH after single, repeated and simultaneous administrations for neutron-capture therapy of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ichikawa, H. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan)], E-mail: ichikawa@pharm.kobegakuin.ac.jp; Taniguchi, E. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan); Fujimoto, T. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Fukumori, Y. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan)

    2009-07-15

    The effect of administration mode of L-BPA and BSH on the biodistribution in the melanoma-bearing hamsters was investigated. In single intravenous (i.v.) administration, BSH (100 mg BSH/kg) showed no significant retention of {sup 10}B in all the tissues, including tumors, while long-term retention of {sup 10}B in the tumor, muscle and brain was observed with L-BPA (500 mg BPA/kg). The dose escalation of L-BPA and the simultaneous single administration of L-BPA and BSH were not so effective at increasing boron accumulation in tumor after bolus i.v. injection. The boron concentration in tumor was 41 {mu}g B/g after single bolus i.v. injection even at the dose of 1000 mg BPA/kg. In contrast, two sequential bolus i.v. injections of L-BPA with the dose of 500 mg BPA/kg each was found to be effective at increasing {sup 10}B accumulation in the tumor; the maximum {sup 10}B concentration in the tumor reached 52 {mu}g B/g at 3 h after the second i.v. injection.

  16. A supersulfated low-molecular-weight heparin (IK-SSH) increases plasma levels of free and total tissue factor pathway inhibitor after intravenous and subcutaneous administration in humans.

    Science.gov (United States)

    Kaiser, B; Glusa, E; Hoppensteadt, D A; Breddin, H K; Amiral, J; Fareed, J

    1998-09-01

    Unfractionated as well as low-molecular-weight heparins (LMWH) are known to cause an increase in blood levels of tissue factor pathway inhibitor (TFPI). To study the effect of a newly developed supersulfated LMWH (IK-SSH, Iketon Farmaceutici) on TFPI concentrations in human plasma, the compound was injected into volunteers at doses of 0.14, 0.33 and 0.66 mg/kg intravenously or 0.33, 0.66 and 1.0 mg/kg subcutaneously. At certain known times blood was drawn and plasma levels of both total and free TFPI were measured using enzyme-linked immunosorbent assay methodology. Baseline plasma concentrations of TFPI were 72.2+/-3.1 ng/ml for total and 10.8+/-0.8 ng/ml for free TFPI. Intravenous or subcutaneous injection of IK-SSH led to a strong and long-lasting rise in TFPI levels which were increased more than 5-fold for total TFPI and more than 30-fold for free TFPI. Maximum TFPI levels were reached 5-10 min after intravenous and 60 min after subcutaneous administration. IK-SSH caused prolongation of ex-vivo clotting times in the APTT and Heptest assay, whereas thrombin time was not affected. Anticoagulant actions of IK-SSH showed a significant correlation to plasma concentrations of TFPI and they are thought to be based at least partially on the release of TFPI from vascular sites.

  17. Repeated Administration of Mercury Intensifies Brain Damage in Multiple Sclerosis through Mitochondrial Dysfunction

    Science.gov (United States)

    Kahrizi, Farzad; Salimi, Ahmad; Noorbakhsh, Farshid; Faizi, Mehrdad; Mehri, Freshteh; Naserzadeh, Parvaneh; Naderi, Nima; Pourahmad, Jalal

    2016-01-01

    In this study we investigated the additive effect of mercury on the brain mitochondrial dysfunction in experimental autoimmune encephalomyelitis (EAE) model. Experimental animals (female C57BL/6 mice) are divided into four groups (n = 8); control, Hg, EAE, EAE with Hg. EAE model of MS induced by injecting myelin oligodendrocyte glycoprotein (MOG). Neurobehavioral alterations are recorded and then mice were sacrificed at day 28 and brain mitochondria were isolated and mitochondrial toxicity parameters including mitochondrial swelling, reactive oxygen species (ROS) formation, collapse of mitochondrial membrane potential (MMP) and cytochrome c release were measured. Our results showed that repeated treatment of mercury following induction of EAE in mice significantly increased the neurobehavioral scores, as well as mitochondrial toxicity through ROS formation, mitochondrial swelling, collapse of MMP and cytochrome c release. Our findings proved that repeated exposure with mercury accelerates progression of MS through mitochondrial damage related to oxidative stress and finally apoptosis.

  18. Evaluation of statistical tools used in short-term repeated dose administration toxicity studies with rodents.

    Science.gov (United States)

    Kobayashi, Katsumi; Pillai, K Sadasivan; Sakuratani, Yuki; Abe, Takemaru; Kamata, Eiichi; Hayashi, Makoto

    2008-02-01

    In order to know the different statistical tools used to analyze the data obtained from twenty-eight-day repeated dose oral toxicity studies with rodents and the impact of these statistical tools on interpretation of data obtained from the studies, study reports of 122 numbers of twenty-eight-day repeated dose oral toxicity studies conducted in rats were examined. It was found that both complex and easy routes of decision trees were followed for the analysis of the quantitative data. These tools include Scheffe's test, non-parametric type Dunnett's and Scheffe's tests with very low power. Few studies used the non-parametric Dunnett type test and Mann-Whitney's U test. Though Chi-square and Fisher's tests are widely used for analysis of qualitative data, their sensitivity to detect a treatment-related effect is questionable. Mann-Whitney's U test has better sensitivity to analyze qualitative data than the chi-square and Fisher's tests. We propose Dunnett's test for analysis of quantitative data obtained from twenty-eight-day repeated dose oral toxicity tests and for qualitative data, Mann-Whitney's U test. For both tests, one-sided test with p=0.05 may be applied.

  19. Intravenous magnetic resonance arthrography of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Hyeon; Lee, Young Uk; Suh, Jong Dae; Lee, Seung Hee; Kim, Dong Joo [Kangbuk Samsung Hospital, Seoul (Korea, Republic of)

    1995-10-15

    Knee MR images were repeatedly obtained after intravenous administration of gadopentetate dimeglumine to evaluate the arthrographic effect and to determine the optimal scan timing and technique. Sagittal T1-weighted (650/15) sequences were repeated before and after intravenous gadolinium enhancement in 26 patients who were divided into exercise (14/26) and nonexercise (12/26) groups. Fourteen patients in exercise group were allowed to move the affected knee joint actively for 10 minutes immediately after the first post-enhancement scan and before repeating scans. The signal intensities in central and peripheral portions of the joint were measured and compared between these two groups. In all cases, enhancement of joint fluid began at peripheral portion and progressed toward central portion. The diffusion rate in exercise group was far faster than that in nonexercise group and homogeneous arthrographic image was revealed within 10 minutes after completion of joint movement. The arthrographic effect continued and the rate of signal decrease was quite slow. MR arthrographic image of knee joint can be obtained within 10 minutes after completion of a few minute exercise following intravenous injection of gadopentetate dimeglumine. Intravenous MR arthrography is expected to become an useful method as a convenient alternative to direct MR arthrography.

  20. Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumor-burdened lymph nodes after intravenous and subcutaneous administration in rats.

    Science.gov (United States)

    Kaminskas, Lisa M; McLeod, Victoria M; Ascher, David B; Ryan, Gemma M; Jones, Seth; Haynes, John M; Trevaskis, Natalie L; Chan, Linda J; Sloan, Erica K; Finnin, Benjamin A; Williamson, Mark; Velkov, Tony; Williams, Elizabeth D; Kelly, Brian D; Owen, David J; Porter, Christopher J H

    2015-02-02

    The current study sought to explore whether the subcutaneous administration of lymph targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumor activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumor-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumor growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumor-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumor activity, possibly suggesting constrained drug release at the site of action.

  1. Repeated Intrathecal Triamcinolone Acetonide Administration in Progressive Multiple Sclerosis: A Review

    Directory of Open Access Journals (Sweden)

    Mazen Abu-Mugheisib

    2011-01-01

    Full Text Available At the present time, anti-inflammatory, immunomodulatory, or immunosuppressive treatments of multiple sclerosis (MS are mainly effective in the early phases of the disease but are of less advantage in progressive phases. Current therapeutic strategies of both primary and secondary progressive MS are rare. One alternative may be intrathecal application of triamcinolone acetonide (TCA. Number of papers deal with advantages and disadvantages of intrathecal administration in MS. Former trials lacked detailed selection of MS patients, with small sample sizes, low steroid dosages, and only a small number of intrathecal administration of short acting steroids. The present paper summarizes recent trials performed following a different treatment regime. They were conducted in patients with progressive MS suffering mainly from spinal symptoms and documented a significant improvement of EDSS and walking distance (WD. Intrathecal TCA administration is a proposal to take into account as one therapy option in patients with a progressive clinical course and predominantly spinal symptoms.

  2. Gadolinium deposition within the dentate nucleus and globus pallidus after repeated administrations of gadolinium-based contrast agents - current status

    Energy Technology Data Exchange (ETDEWEB)

    Stojanov, Dragan [University of Nis, Faculty of Medicine, Nis (Serbia); Center for Radiology, Nis (Serbia); Aracki-Trenkic, Aleksandra [Center for Radiology, Nis (Serbia); Benedeto-Stojanov, Daniela [University of Nis, Faculty of Medicine, Nis (Serbia)

    2016-05-15

    Gadolinium-based contrast agents (GBCAs) have been used clinically since 1988 for contrast-enhanced magnetic resonance imaging (CE-MRI). Generally, GBCAs are considered to have an excellent safety profile. However, GBCA administration has been associated with increased occurrence of nephrogenic systemic fibrosis (NSF) in patients with severely compromised renal function, and several studies have shown evidence of gadolinium deposition in specific brain structures, the globus pallidus and dentate nucleus, in patients with normal renal function. Gadolinium deposition in the brain following repeated CE-MRI scans has been demonstrated in patients using T1-weighted unenhanced MRI and inductively coupled plasma mass spectroscopy. Additionally, rodent studies with controlled GBCA administration also resulted in neural gadolinium deposits. Repeated GBCA use is associated with gadolinium deposition in the brain. This is especially true with the use of less-stable, linear GBCAs. In spite of increasing evidence of gadolinium deposits in the brains of patients after multiple GBCA administrations, the clinical significance of these deposits continues to be unclear. Here, we discuss the current state of scientific evidence surrounding gadolinium deposition in the brain following GBCA use, and the potential clinical significance of gadolinium deposition. There is considerable need for further research, both to understand the mechanism by which gadolinium deposition in the brain occurs and how it affects the patients in which it occurs. (orig.)

  3. Optimization of health-care organization and perceived improvement of patient comfort by switching from intra-venous BU four-times-daily infusions to a once-daily administration scheme in adult hematopoietic stem cell recipients.

    Science.gov (United States)

    Xhaard, A; Rzepecki, P; Valcarcel, D; Santarone, S; Fürst, S; Serrano, D; De Angelis, G; Krüger, W; Scheid, C

    2014-04-01

    Previous studies have shown an equivalent pharmacokinetic profile between four-times-daily (4QD) and once-daily (QD) administration of intra-venous (IV) BU, without increased toxicity. We assess the impact of a switch in IV BU from a 4QD to a QD schedule, in terms of health-care organization, staff working conditions, quality of care dispensed and perceived patient comfort. Clinicians, nurses and pharmacists from nine allogeneic transplantation units in five European countries were interviewed face to face. Overall perception of QD versus 4QD BU was very positive. Both administration schemes were evaluated to be equally efficaciousZ. QD BU was perceived to be safer and more convenient. Clinicians and nurses perceived that patient comfort was improved, due to fewer complications associated with repeated infusions, and avoiding night infusions associated with stress, anxiety and decreased quality of sleep. Switching from 4QD to QD BU had a significant impact on health-care organization, with a better integration in the overall management and usual timelines in the pharmacies and transplantation units. Time spent to prepare and administer BU was significantly reduced, leading to potential financial savings that merit further assessment and would be of particular interest in the current economic climate.

  4. Distribution of β-carotene-encapsulated polysorbate 80-coated poly(D, L-lactide-co-glycolide nanoparticles in rodent tissues following intravenous administration

    Directory of Open Access Journals (Sweden)

    Miyazawa T

    2015-11-01

    Full Text Available Taiki Miyazawa,1,2 Kiyotaka Nakagawa,1,2 Takahiro Harigae,2 Ryo Onuma,2 Fumiko Kimura,2 Tomoyuki Fujii,3 Teruo Miyazawa4,5 1Vascular Biology Laboratory, Jean Mayer USDA (United States Department of Agriculture-Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA; 2Food and Biodynamic Chemistry Laboratory, 3Terahertz Optical & Food Engineering Laboratory, Graduate School of Agricultural Science, 4Food and Biotechnology Innovation Project, New Industry Creation Hatchery Center (NICHe, 5Food and Health Science Research Unit, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan Purpose: Biodegradable nanoparticles (NPs composed of poly(D, L-lactide-co-glycolide (PLGA have attracted considerable attention as delivery systems of drugs and antioxidative compounds, such as β-carotene (BC. Intravenous (IV administration of BC-containing PLGA-NPs (BC-PLGA-NPs coated with polysorbate 80 (PS80 has been shown to effectively deliver BC to the brain. However, the whole-body distribution profile of BC is still not clear. Therefore, we investigated the accumulation of BC in various organs, including the brain, following IV administration of PS80-coated BC-PLGA-NPs in rats.Methods: PS80-coated and uncoated BC-PLGA-NPs were prepared by solvent evaporation, and administered intravenously to Sprague Dawley rats at a BC dose of 8.5 mg/rat. Accumulation of BC in various organs (brain, heart, liver, lungs, and spleen and blood plasma was evaluated by high performance liquid chromatography with ultraviolet (UV detection, 1 hour after administration.Results: We prepared PS80-coated BC-PLGA-NPs with an entrapment efficiency of 14%, a particle size of 260 nm, and a zeta potential of -26 mV. Coating with PS80 was found to result in significant accumulation of BC in the lungs, rather than in the brain and other tissues. Further, plasma levels of BC in the PS80-coated BC-PLGA-NP group were much lower than those of the uncoated

  5. The influence of repeated administration of poloxamer 407 on serum lipoproteins and protease activity in mouse liver and heart.

    Science.gov (United States)

    Korolenko, Tatyana A; Tuzikov, Fedor V; Johnston, Thomas P; Tuzikova, Natalia A; Kisarova, Yana A; Zhanaeva, Svetlana Ya; Alexeenko, Tatyana V; Zhukova, Natalia A; Brak, Ivan V; Spiridonov, Victor K; Filjushina, Elena E; Cherkanova, Marina S; Monoszon, Anna A

    2012-11-01

    The effects of repeated administration of poloxamer 407 (P-407) on lipoprotein-cholesterol (LP-C) and lipoprotein-triglyceride (LP-TG) fractions and subfractions, as well as the effect on liver and heart proteases, were studied. Repeated administration of P-407 to male CBA mice resulted in a model of atherosclerosis with increased diastolic blood pressure; there was a drastic increase in total serum cholesterol and especially TG. A novel small-angle X-ray scattering method for the determination of the fractional and subfractional composition of LP-C and LP-TG was used. In chronically P-407-treated mice, P-407 significantly increased atherogenic low-density lipoprotein C (LDL-C) fractions, as well as intermediate-density lipoprotein C (IDL-C), and LDL₁₋₃-C subfractions, and very-low-density lipoprotein-C (VLDL-C) fractions, as well as VLDL₁₋₂-C and VLDL₃₋₅-C subfractions), to a lesser extent, the total anti-atherogenic high-density lipoprotein C (HDL-C) fraction, as well as HDL₂-C and HDL₃-C subfractions. Additionally, we demonstrated an increase in the serum chitotriosidase activity, without significant changes in serum matrix metalloprotease (MMP) activity. Morphological changes observed in P-407-treated mice included atherosclerosis in the heart and storage syndrome in the liver macrophages. P-407 significantly increased the activity of cysteine, aspartate proteases, and MMPs in the heart, and only the activity of cathepsin B and MMPs in the liver of mice. Thus, repeated administration of P-407 to mice induced atherosclerosis secondary to sustained dyslipidemia and formation of foamy macrophages in liver, and also modulated the activity of heart and liver proteases.

  6. HPLC determination of five polyphenols in rat plasma after intravenous administration of hawthorn leaves extract and its application to pharmacokinetic study.

    Science.gov (United States)

    Wang, Si-Yuan; Chai, Ji-Yan; Zhang, Wen-Jie; Liu, Xun; DU, Yang; Cheng, Zhong-Zhe; Ying, Xi-Xiang; Kang, Ting-Guo

    2010-11-01

    A simple and specific HPLC-UV method was developed to simultaneously determine five active compounds including vitexin-4"-O-glucoside (VG), vitexin-2"-O-rhamnoside (VR), vitexin (VIT), rutin (RUT) and hyperoside (HP) in rat plasma after intravenous administrating the hawthorn leaves extract (HLE). With baicalin as internal standard (I.S.), sample pretreatment involved a one-step extraction with methanol of 0.2 ml plasma. The HPLC assay was carried out using a Phenomsil C18 analytical column with UV detection at 332 nm. The mobile phase consisted of methanol-acetonitrile-tetrahydrofuran-1% glacial acetic acid (6:1.5:18.5:74, v/v/v/v). The calibration curves were liner over the range of 2.030-500.5, 0.1513-75.64, 0.2507-12.54, 0.5128-25.64 and 0.4032-20.16 µg/ml for VG, VR, VIT, RUT and HP, respectively. The relative standard deviations (RSD) of the intra- and inter-day precisions for the analysis of the five analytes were between 1.0 and 8.9% with accuracies (relative error) below 8.2% for the analysis of the five analytes. The average extraction recoveries of five analytes were more than 82.67 ± 4.74%. The HPLC method herein described was fully validated and successfully applied to the pharmacokinetic studies after intravenous administration of HLE solution to rats over three doses.

  7. Addition of lacal anesthetics to contrast media. Pt. 2. Increase of acute mortality in mice with intravenous contrast administration

    Energy Technology Data Exchange (ETDEWEB)

    Nilsson, P.; Almen, T.; Golman, K.; Jonsson, K.; Nyman, U.

    The acute intravenous toxicity (i.v. LD/sub 50/) of solutions of the ratio 1.5 contrast media metrizoate or diatrizoate and the ratio 3.0 contrast medium metrizamide was determined in mice with and without the addition of local anesthetics to the solutions. The two local anesthetics mepivacaine or lidocaine were added to final concentrations up to 2.0 mg/ml of the contrast medium solutions. This corresponds to clinically used concentrations. All additions of local anesthetics to the solutions increased the mortalities caused by the contrast medium solutions. Addition of local anesthetics to a final concentration of 2 mg/ml approximately doubled the acute intravenous toxicity of the contrast media. The ratio 3 contrast media produce less hypertonic solutions than the ratio 1.5 contrast media and should be preferred for angiography because they cause less pain and do not require the addition of local anesthetics which increase the acute toxicity of the solutions.

  8. Effects of intravenous administration of allogenic bone marrow- and adipose tissue-derived mesenchymal stem cells on functional recovery and brain repair markers in experimental ischemic stroke

    Science.gov (United States)

    2013-01-01

    Introduction Stem cell therapy can promote good recovery from stroke. Several studies have demonstrated that mesenchymal stem cells (MSC) are safe and effective. However, more information regarding appropriate cell type is needed from animal model. This study was targeted at analyzing the effects in ischemic stroke of acute intravenous (i.v.) administration of allogenic bone marrow- (BM-MSC) and adipose-derived-stem cells (AD-MSC) on functional evaluation results and brain repair markers. Methods Allogenic MSC (2 × 106 cells) were administered intravenously 30 minutes after permanent middle cerebral artery occlusion (pMCAO) to rats. Infarct volume and cell migration and implantation were analyzed by magnetic resonance imaging (MRI) and immunohistochemistry. Function was evaluated by the Rogers and rotarod tests, and cell proliferation and cell-death were also determined. Brain repair markers were analyzed by confocal microscopy and confirmed by western blot. Results Compared to infarct group, function had significantly improved at 24 h and continued at 14 d after i.v. administration of either BM-MSC or AD-MSC. No reduction in infarct volume or any migration/implantation of cells into the damaged brain were observed. Nevertheless, cell death was reduced and cellular proliferation significantly increased in both treatment groups with respect to the infarct group. At 14 d after MSC administration vascular endothelial growth factor (VEGF), synaptophysin (SYP), oligodendrocyte (Olig-2) and neurofilament (NF) levels were significantly increased while those of glial fiibrillary acid protein (GFAP) were decreased. Conclusions i.v. administration of allogenic MSC - whether BM-MSC or AD-MSC, in pMCAO infarct was associated with good functional recovery, and reductions in cell death as well as increases in cellular proliferation, neurogenesis, oligodendrogenesis, synaptogenesis and angiogenesis markers at 14 days post-infarct. PMID:23356495

  9. Evaluating the Frequency of Errors in Preparation and Administration of Intravenous Medications in the Intensive Care Unit of Shahid-Sadoughi Hospital in Yazd

    Directory of Open Access Journals (Sweden)

    SeyedMojtaba Sohrevardi

    2015-10-01

    Full Text Available Background: In most Iranian hospitals, the nurses in the wards prepare intravenous (IV drugs and unfortunately pharmacists are not involved in this process. The severity of the patients in Intensive Care Unit (ICU heightens the risk of errors. More over the frequency of using IV drugs in this unit is high, so we decided to determine the frequency and types of errors, which occur in the preparation and administration of commonly, used IV medications in an ICU.Method: A prospective cross sectional study was performed from November 2013 to August 2014, in the intensive care unit in Shahid-Sadoughi hospital in Yazd. Medication errors occurred in the process of preparation and administration of IV drugs, were recorded by a pharmacy student and were evaluated by direct observation, according to the method established by Barker and McConnell.Results: A total number of 843 intravenous doses were evaluated. The most common type of error (34.26% was the injection of IV doses faster than the recommended rate followed by preparation (15.69%, administration (9.23% and compatibility with doctor’s order (6.24%. Amikacin was the most common drug involved in errors (41.67%. Most of errors were occurred at afternoon (8 p.m, 28.36%.Conclusion: According to our study the rate of errors in preparation and administration of IV drugs was high in this ICU. Employing more nurses, using developed medical instruments and clinical pharmacists can help to decrease these errors and improve the quality of patient care.

  10. The comparative pharmacokinetics of two pyrrolizidine alkaloids, senecionine and adonifoline, and their main metabolites in rats after intravenous and oral administration by UPLC/ESIMS.

    Science.gov (United States)

    Wang, Changhong; Li, Yan; Gao, Jiangguo; He, Yuqi; Xiong, Aizhen; Yang, Li; Cheng, Xuemei; Ma, Yueming; Wang, Zhengtao

    2011-07-01

    Pyrrolizidine alkaloids (PAs) are considered to be one of the most hepatotoxic groups of compounds of plant origin and are present in about 3% of the world's flowering plants. Most PAs represent a considerable health hazard to both livestock and humans through the consumption of plants and PA-contaminated products such as milk, honey, herbal teas, and medicines. This study determined the differences in the in vivo pharmacokinetic behavior of senecionine (SEN), adonifoline (ADO), and their main metabolites in rats after intravenous administration and oral administration by ultraperformance liquid chromatography/electrospray ionization mass spectrometry. Upon intravenous administration and oral administration of SEN and ADO, significant differences in pharmacokinetics were observed, with the SEN and ADO being absorbed fast with lower bioavailability and being quickly metabolized to PA N-oxides and hydroxylation products of PAs or their N-oxides. It could be seen that the plasma concentration ratio of senecionine N-oxide (SEN-NO) to SEN (C (SEN-NO)/C (SEN)) was significantly larger than that for adonifoline N-oxide (ADO-NO) and ADO (C (ADO-NO)/C (ADO)) (P < 0.001) for both dosing routes in rats. The high N-oxygenation activity and extensive toxicity of SEN, compared with ADO, in rats raised the question of whether or not the higher metabolic rate of SEN in rats in vivo was related to its potent toxicity. The toxicity of SEN-NO and ADO-NO needs to be evaluated further and compared in vitro/in vivo. This study was most helpful for interpreting the metabolism of metabolic bioactivation and detoxication, and toxicity differences among SEN, ADO and other PAs.

  11. Acute liver failure in a term neonate after repeated paracetamol administration

    Directory of Open Access Journals (Sweden)

    Fabio Bucaretchi

    2014-03-01

    Full Text Available Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L, hypoglycemia (18mg/dL, increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL after receiving oral paracetamol (10mg/kg/dose every 4 hours for three consecutive days (total dose around 180mg/kg; serum concentration 36-48 hours after the last dose of 77µg/ mL. Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day 34. The follow-up revealed full recovery of clinical and of laboratory findings of hepatic function. Comments: The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system and the increased ability to synthesize glutathione - which provides greater resistance after overdoses -, it is possible to produce hepatotoxic metabolites (N-acetyl-p-benzoquinone that cause hepatocellular damage, if glutathione sources are depleted. Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses for more than two to three days.

  12. Repeated oral administration of capsaicin increases anxiety-like behaviours with prolonged stress-response in rats

    Indian Academy of Sciences (India)

    Y-J Choi; J Y Kim; S B Yoo; J-H Lee; J W Jahng

    2013-09-01

    This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02% capsaicin into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of capsaicin. Stereotypy counts and rostral grooming were significantly increased, and caudal grooming decreased, in capsaicin-treated rats during the ambulatory activity test. In elevated plus maze test, not only the time spent in open arms but also the percent arm entry into open arms was reduced in capsaicin-treated rats compared with control rats. In forced swim test, although swimming duration was decreased, struggling increased in the capsaicin group, immobility duration did not differ between the groups. Repeated oral capsaicin did not affect the basal levels of plasma corticosterone; however, the stress-induced elevation of plasma corticosterone was prolonged in capsaicin treated rats. Oral capsaicin exposure significantly increased c-Fos expression not only in the nucleus tractus of solitarius but also in the paraventricular nucleus. Results suggest that repeated oral exposure to capsaicin increases anxiety-like behaviours in rats, and dysfunction of the hypothalamic-pituitary-adrenal axis may play a role in its pathophysiology.

  13. Effect of Repeated Administration of hCG on Ovarian Response in PMSG-superovulated Ouled Djellal Ewes (Algeria

    Directory of Open Access Journals (Sweden)

    Lamraoui, R.

    2014-01-01

    Full Text Available The objective of this study was to evaluate the effect of repeated administration of hCG on ovarian response in PMSG-superovulated ewes. Intravaginal pessaries containing 40 mg fluorogestone acetate (FGA were inserted in all ewes (n=9 and remained in situ for 14 days. Two days prior to pessary removal, all ewes were treated with 1000 IU of PMSG. On the day of sponge removal (day 0, the females were randomly assigned to 2 treatments. The first group (n=3 did not receive any hCG, while the second group (n=6 treated inter-muscular with hCG (500 IU during days 0-2. On day 8, laparotomy was performed to assess numbers of corpora lutea (CL and anovulatory follicles (AF. Blood samples were collected for analysis of serum progesterone (P4 using radioimmunoassay (RIA method. The results obtained for first and second group was in number of CL (6.33±1.15 and 10.50±5.54, number of AF (2 ±3.46 and 4.16±5.70, then the levels of P4 (5.75± 4.45 and 13.22±6.80 ng/ml, respectively. These results indicate that the repeated administration of hCG post-sponge removal increases number of CL and improves luteal function in ewes after PMSG-superovulatory treatment.

  14. Liquid chromatographic determination and depletion profile of oxytetracycline in milk after repeated intramuscular administration in sheep.

    Science.gov (United States)

    Fletouris, Dimitrios J; Papapanagiotou, Elias P; Nakos, Dimitrios S

    2008-12-01

    A simple, rapid and specific ion-pair liquid chromatographic method for the routine determination of the marker residue of oxytetracycline in sheep milk, at levels as low as 20 microg/kg, has been developed. Milk samples were acidified and extracted with acetonitrile. The extracts were purified by treatment with ammonium sulphate and concentrated into diluted phosphoric acid. Separation was carried out isocratically on a Nucleosil C(18) column using a mobile phase that contained both positively and negatively charged pairing ions. The in-house validated method gave overall recoveries and overall relative standard deviations better than 86% and 4.6%, respectively. The method was successfully applied to study the depletion of oxytetracycline in sheep milk and to estimate the withdrawal period after intramuscular administration of a commercial oxytetracycline formulation.

  15. Behavioral and neurochemical effects of repeated MDMA administration during late adolescence in the rat.

    Science.gov (United States)

    Cox, Brittney M; Shah, Mrudang M; Cichon, Teri; Tancer, Manuel E; Galloway, Matthew P; Thomas, David M; Perrine, Shane A

    2014-01-01

    Adolescents and young adults disproportionately abuse 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy'); however, since most MDMA research has concentrated on adults, the effects of MDMA on the developing brain remain obscure. Therefore, we evaluated place conditioning to MDMA (or saline) during late adolescence and assessed anxiety-like behavior and monoamine levels during abstinence. Rats were conditioned to associate 5 or 10mg/kg MDMA or saline with contextual cues over 4 twice-daily sessions. Five days after conditioning, anxiety-like behavior was examined with the open field test and brain tissue was collected to assess serotonin (5-hydroxytryptamine, 5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the dorsal raphe, amygdala, and hippocampus by high-pressure liquid chromatography (HPLC). In a separate group of rats, anxiety-like and avoidant behaviors were measured using the light-dark box test under similar experimental conditions. MDMA conditioning caused a place aversion at 10, but not at 5, mg/kg, as well as increased anxiety-like behavior in the open field and avoidant behavior in light-dark box test at the same dose. Additionally, 10mg/kg MDMA decreased 5-HT in the dorsal raphe, increased 5-HT and 5-HIAA in the amygdala, and did not alter levels in the hippocampus. Overall, we show that repeated high (10mg/kg), but not low (5mg/kg), dose MDMA during late adolescence in rats increases anxiety-like and avoidant behaviors, accompanied by region-specific alterations in 5-HT levels during abstinence. These results suggest that MDMA causes a region-specific dysregulation of the serotonin system during adolescence that may contribute to maladaptive behavior.

  16. Efficacy of post-operative analgesia after posterior lumbar instrumented fusion for degenerative disc disease: a prospective randomized comparison of epidural catheter and intravenous administration of analgesics

    Directory of Open Access Journals (Sweden)

    Torsten Kluba

    2010-04-01

    Full Text Available This prospective study aimed to compare the efficacy of epidural (EDA versus intravenous (PCA application of analgesics after lumbar fusion. Fifty-two patients scheduled for elective posterior instrumented lumbar fusion were randomized into two groups. EDA patients received an epidural catheter intraoperatively, and administration of ropivacain and sulfentanil was started after a normal post-operative wake-up test in the recovery room area. PCA patients received intravenous opioids in the post-operative period. Differences between EDA and PCA groups in terms of patient satisfaction with respect to pain relief were not significant. Nevertheless, EDA patients reported less pain on the third day after surgery. There were significantly more side effects in the EDA group, including complete reversible loss of sensory function and motor weakness. There were no major side effects, such as infection or persisting neurological deficits, in either group. The routine use of epidural anesthesia for lumbar spine surgery has too many risks and offers very little advantage over PCA.

  17. Steady-state carbamazepine pharmacokinetics following oral and stable-labeled intravenous administration in epilepsy patients: effects of race and sex.

    Science.gov (United States)

    Marino, S E; Birnbaum, A K; Leppik, I E; Conway, J M; Musib, L C; Brundage, R C; Ramsay, R E; Pennell, P B; White, J R; Gross, C R; Rarick, J O; Mishra, U; Cloyd, J C

    2012-03-01

    Carbamazepine is a widely prescribed antiepileptic drug. Owing to the lack of an intravenous formulation, its absolute bioavailability, absolute clearance, and half-life in patients at steady state have not been determined. We developed an intravenous, stable-labeled (SL) formulation in order to characterize carbamazepine pharmacokinetics in patients. Ninety-two patients received a 100-mg infusion of SL-carbamazepine as part of their morning dose. Blood samples were collected up to 96 hours after drug administration. Plasma drug concentrations were measured with liquid chromatography-mass spectrometry, and concentration-time data were analyzed using a noncompartmental approach. Absolute clearance (l/hr/kg) was significantly lower in men (0.039 ± 0.017) than in women (0.049 ± 0.018; P = 0.007) and in African Americans (0.039 ± 0.017) when compared with Caucasians (0.048 ± 0.018; P = 0.019). Half-life was significantly longer in men than in women as well as in African Americans as compared with Caucasians. The absolute bioavailability was 0.78. Sex and racial differences in clearance may contribute to variable dosing requirements and clinical response.

  18. Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal Uptake of Acyclovir Following Oral Dosing

    Directory of Open Access Journals (Sweden)

    Ravi S.Talluri

    2009-10-01

    Full Text Available Objective: To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV in rats. Methods: Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV, L-valine- D-valine-acyclovir (LDACV and D-valine-L-valine acyclovir (DLACV prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results: Following i.v. administration, the area under the curve (AUC in µM*min of generated ACV was in the order of LACV › LDACV › DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 µM*min, respectively. DLACV exhibited poor oral absorption. Cmax (µM and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions: LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV. Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.

  19. Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model

    Directory of Open Access Journals (Sweden)

    Noriaki Nagai

    2015-12-01

    Full Text Available It was reported that cilostazol (CLZ suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZnano dispersion; particle size 81 ± 59 nm, mean ± S.D., and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice. The pharmacokinetics of injections of CLZnano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZnano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZnano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZnano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZnano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage.

  20. Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats

    Science.gov (United States)

    Calatrava-Ferreras, Lucía; Gonzalo-Gobernado, Rafael; Herranz, Antonio S.; Reimers, Diana; Montero Vega, Teresa; Jiménez-Escrig, Adriano; Richart López, Luis Alberto; Bazán, Eulalia

    2012-01-01

    Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders. PMID:23150735

  1. DEXAMETHASON ADMINISTRATION IN INTRAVENOUS REGIONAL ANESTHESIA: ITS AFFECT ON POST OPERATIVE PAIN A RANDOMIZED DOUBLE BLINDED CLINICAL TRIAL

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    H SARYAZDI

    2002-03-01

    Full Text Available Introduction. Intravenous regional anesthesia (IVRA is one of the successful method of anesthesia in relief of pain of surgery. It has a multiple advantages including feasibility, rapidity of recovery, rapid onest, muscular relaxation and controllable onset of anesthesia. But this technique dose not relief postoperative pain. In the previous studies it had been tried to add some drugs to local anesthetic in IVRA for relief postoperative pain. Methods. One hundred and ten adult patients in class I and II ASA scheduled for elective operation of unilatral upper extrimeties under IVRA, randomly allocated into interventional and control groups. NRA was done with Lidocaine 0.5 percent with or without dexamethason. Postoperative pain was assessed by visual analogue scale. Results. Addition of dexamethason to local anesthetic in IVRA resulted in better tolleration of turniquate pain and reduced VAS score. Frequency of severe postoperative pain was reduced in case group. Discussion. It seems that dexamethason usage in local anesthetic in IVRA prevents sever postoperative pain in patients. The results of this study is simillar to the study wich added ketorolac to IVRA solution.

  2. Development of a population pharmacokinetics-based sampling schedule to target daily intravenous busulfan for outpatient clinic administration.

    Science.gov (United States)

    Salinger, David H; Vicini, Paolo; Blough, David K; O'Donnell, Paul V; Pawlikowski, Matthew A; McCune, Jeannine S

    2010-11-01

    Therapeutic drug monitoring of daily intravenous (IV) busulfan currently requires hospital admission. Population pharmacokinetic modeling and determination of an optimal pharmacokinetic sampling schedule over 6 hours could allow for personalizing these busulfan doses in the outpatient clinic. A retrospective evaluation of daily IV busulfan pharmacokinetics was conducted in 37 adults. SPK and NONMEM software were used to estimate the population pharmacokinetic parameters. Subsequent to model building, the area under the concentration-time curve (AUC) was computed using NONMEM. A 1-compartment model best fit the data. The optimal 6-hour outpatient sampling schedule was constructed using a simulation approach that sought to minimize scaled mean squared error for the clearance and volume parameters for each simulated individual. The best sampling times were 2.75, 3, 3.25, 5.5, 5.75, and 6 hours from the start of a 3-hour infusion. With these sampling times, the maximum a posteriori (MAP) Bayesian estimation was superior to maximum likelihood estimation with more samples. An individual patient's busulfan AUC and pharmacokinetic parameters may be accurately estimated with an outpatient sampling schedule that is used in conjunction with MAP Bayesian estimation, with a parameter prior based on population pharmacokinetic modeling. Prospective validation of this approach is needed.

  3. Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats

    Directory of Open Access Journals (Sweden)

    Lucía Calatrava-Ferreras

    2012-01-01

    Full Text Available Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders.

  4. Repeated Oral Administration of Oleanolic Acid Produces Cholestatic Liver Injury in Mice

    Directory of Open Access Journals (Sweden)

    Yasha Xu

    2013-03-01

    Full Text Available Oleanolic acid (OA is a triterpenoid and a fantastic molecule with many beneficial effects. However, high-doses and long-term use can produce adverse effects. This study aimed to characterize the hepatotoxic potential of OA. Mice were given OA at doses of 100–3,000 µmol/kg (45–1,350 mg/kg, po for 10 days, and the hepatotoxicity was determined by serum biochemistry, histopathology, and toxicity-related gene expression via real-time RT-PCR. Animal body weight loss was evident at OA doses of 1,000 µmol/kg and above. Serum alanine aminotransferase activities were increased in a dose-dependent manner, indicative of hepatotoxicity. Serum total bilirubin concentrations were increased, indicative of cholestasis. OA administration produced dose-dependent pathological lesions to the liver, including inflammation, hepatocellular apoptosis, necrosis, and feathery degeneration indicative of cholestasis. These lesions were evident at OA doses of 500 µmol/kg and above. Real-time RT-PCR revealed that OA produced dose-dependent increases in acute phase proteins (MT-1, Ho-1, Nrf2 and Nqo1, decreases in bile acid synthesis genes (Cyp7a1 and Cyp8b1, and decreases in liver bile acid transporters (Ntcp, Bsep, Oatp1a1, Oatp1b2, and Ostβ. Thus, the clinical use of OA and OA-type triterpenoids should balance the beneficial effects and toxicity potentials.

  5. Comparison of the Concentrations of Lidocaine in Different Body Fluids/Tissues after Subarachnoid Space and Intravenous Administration of a Lethal Dose of Lidocaine

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    Nan Zhang

    2015-01-01

    Full Text Available The objective of the study was to compare the concentration of lidocaine in different body fluids/tissues after subarachnoid space and intravenous administrations of a lethal dose of lidocaine. Totally 18 dogs were used in the experiment. Six dogs were given subarachnoid anesthesia, another were given an intravenous injection of a dose of 75 mg/kg weight of lidocaine hydrochloride in 5 min and the last 6 dogs were used as the blank control dogs and given a subarachnoid space injection or a femoral artery injection of the same volume of sodium chloride. As soon as its vital signs disappeared, each dog was dissected and the specimen, such as brain, cerebrospinal fluid (CSF in lateral ventricle, CSF in subarachnoid space, spinal cord (cervical spinal cord, thoracic spinal cord, lumbar spinal cord, and waist spinal cord, heart, lung, liver, spleen, kidney, bile, urine, heart blood, peripheral blood, muscle in injection location, and muscle in no injection location, were collected for analysis of lidocaine immediately. Analysis was performed with gas chromatography-mass spectrometry (GC-MS. From the maximum to the minimum, the order of lidocaine concentration detected in the subarachnoid space-administered dogs was as follows: CSF in subarachnoid space, waist spinal cord, thoracic spinal cord, CSF in lateral ventricle, lumbar spinal cord, cervical spinal cord, lung, kidney, muscle in injection location, heart, brain, spleen, heart blood, liver, peripheral blood, bile, muscle in no injection location, and urine. The order of lidocaine concentration detected in the intravenously administered dogs was as followed: Kidney, heart, lung, spleen, brain, liver, peripheral blood, bile, heart blood, cervical spinal cord, thoracic spinal cord, muscle in injection location, lumbar spinal cord, muscle in no injection location, CSF in subarachnoid space, urine, and CSF in lateral ventricle. The maximum concentration of lidocaine was detected in the subarachnoid

  6. Screening and Confirmatory Analyses of Flunixin in Tissues and Bodily Fluids after Intravenous or Intramuscular Administration to Cull Dairy Cows with or without Lipopolysaccharide Challenge.

    Science.gov (United States)

    Shelver, Weilin L; Smith, David J; Tell, Lisa A; Baynes, Ronald E; Schroeder, J W; Riviere, Jim E

    2016-01-13

    Twenty cull dairy cows (645 ± 83 kg) were treated with 2.2 mg/kg bw flunixin by intravenous (IV) or intramuscular (IM) administration with, or without, exposure to lipopolysaccharide in a two factor balanced design. The usefulness of screening assays to identify violative flunixin levels in a variety of easily accessible ante-mortem fluids in cattle was explored. Two animals with violative flunixin liver residue and/or violative 5-hydroxy flunixin milk residues were correctly identified by a flunixin liver ELISA screen. Oral fluid did not produce anticipated flunixin concentration profiles using ELISA determination. One cow that had liver and milk violative residues, and one cow that had a milk violation at the prescribed withdrawal period were correctly identified by flunixin milk lateral flow analyses. The ratio of urinary flunixin and 5-hydroxy flunixin may be useful for predicting disruption of metabolism caused by disease or other factors potentially leading to violative liver flunixin residues.

  7. Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings.

    Science.gov (United States)

    Li, Jie; Li, Xin; Ren, Yu-Shan; Lv, Yuan-Yuan; Zhang, Jun-Sheng; Xu, Xiao-Li; Wang, Xian-Zhen; Yao, Jing-Chun; Zhang, Gui-Min; Liu, Zhong

    2017-01-01

    Although arctigenin (AG) has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro. In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK) profiles of AG with different drug-delivery manners, including intravenous (i.v), hypodermic injection (i.h), and sublingual (s.l) administration. The data shows that AG exhibited a strong absorption capacity in both rats and beagle dogs (absorption rate 100%), and a strong elimination ability (t1/2 beagle dog (25.9 ± 3.24%) > rat (15.7 ± 9%) > monkey (3.69 ± 0.12%). This systematic investigation of pharmacokinetic profiles of arctigenin (AG) in vivo and in vitro is worthy of further exploration.

  8. Hepatotoxicity assessment of Mn-doped ZnS quantum dots after repeated administration in mice

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    Yang YJ

    2015-09-01

    Full Text Available Yanjie Yang,1,2 Shuang-Yu Lv,2 Bianfei Yu,1 Shuang Xu,1 Jianmin Shen,3 Tong Zhao,1 Haixia Zhang1 1Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou University, Lanzhou, Gansu, 2School of Medicine, Henan University, Kaifeng, Henan, 3Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou, Gansu, People’s Republic of China Abstract: Doped ZnS quantum dots (QDs have a longer dopant emission lifetime and potentially lower cytotoxicity compared to other doped QDs. The liver is the key organ for clearance and detoxification of xenobiotics by phagocytosis and metabolism. The present study was designed to synthesize and evaluate the hepatotoxicity of Mn-doped ZnS QDs and their polyethylene glycol-coated counterparts (1 mg/kg and 5 mg/kg in mice. The results demonstrated that daily injection of Mn-doped ZnS QDs and polyethylene glycol-coated QDs via tail vein for 7 days did not influence body weight, relative liver weight, serum aminotransferases (alanine aminotransferase and aspartate aminotransferase, the levels of antioxidant enzymes (catalase, glutathione peroxidase, and superoxide dismutase, or malondialdehyde in the liver. Analysis of hepatocyte ultrastructure showed that Mn-doped ZnS QDs and polyethylene glycol-coated QDs mainly accumulated in mitochondria at 24 hours after repeated intravenous injection. No damage to cell nuclei or mitochondria was observed with either of the QDs. Our results indicate that Mn-doped ZnS QDs did not cause obvious damage to the liver. This study will assist in the development of Mn-doped ZnS QDs-based bioimaging and biomedical applications in the future. Keywords: liver, serum aminotransferases, antioxidant enzymes, ultrastructure

  9. Systemic and direct nose-to-brain transport pharmacokinetic model for remoxipride after intravenous and intranasal administration

    NARCIS (Netherlands)

    Stevens, Jasper; Ploeger, Bart A; van der Graaf, Piet H; Danhof, Meindert; de Lange, Elizabeth C M

    2011-01-01

    Intranasal (IN) administration could be an attractive mode of delivery for drugs targeting the central nervous system, potentially providing a high bioavailability because of avoidance of a hepatic first-pass effect and rapid onset of action. However, controversy remains whether a direct transport r

  10. Tolerance in the anxiolytic profile following repeated administration of diazepam but not buspirone is associated with a decrease in the responsiveness of postsynaptic 5-HT-1A receptors.

    Science.gov (United States)

    Khan, Asma; Haleem, D J

    2007-12-01

    To understand the role of serotonin (5-hydroxytryptamine; 5-HT)-1A receptors in the treatment of anxiety and the development of tolerance to benzodiazepines the present study was designed to monitor the responsiveness of postsynaptic 5-HT-1A receptors following repeated administration of diazepam and buspirone. Results show that tolerance in the anxiolytic profile is produced following repeated administration (2 weeks) of diazepam (2 mg/kg) but not buspirone (0.5 mg/kg). The behavioral effects of 8-OH-DPAT at a dose of 0.25 mg/kg were monitored 3 days after repeated administration of saline or buspirone or diazepam. The results show that 8-OH-DPAT elicited forepaw treading was smaller in repeated diazepam but not repeated buspirone injected rats, while hyperlocomotive effects of 8-OH-DPAT were smaller in both repeated buspirone and repeated diazepam injected rats. The results suggest that postsynaptic 5-HT-1A receptor-dependent responses were attenuated following long-term administration of diazepam but not buspirone. Role of 5-HT-1A receptors in the development of tolerance to the anxiolytic effects of diazepam but not buspirone is discussed.

  11. Comparison of ELISA and LC-MS/MS for the measurement of flunixin plasma concentrations in beef cattle after intravenous and subcutaneous administration.

    Science.gov (United States)

    Shelver, Weilin L; Tell, Lisa A; Wagner, Sarah; Wetzlich, Scott E; Baynes, Ronald E; Riviere, Jim E; Smith, David J

    2013-03-20

    Eight cattle (288 ± 22 kg) were treated with 2.2 mg/kg of body weight of flunixin free acid in a crossover design by subcutaneous (SC) and intravenous (IV) administration. After a minimum 1:10 dilution with 50 mM phosphate buffer, a commercial immunoassay was adapted to determine plasma concentrations of flunixin. The limit of detection was 0.42 ng/mL and the working range was 0.76-66.4 ng/mL when adjusted with the dilution factor. Plasma samples were extracted using mixed-mode cation exchange solid phase extraction prior to the LC-MS/MS analyses. The linear calibration curve for LC-MS/MS was 0.5-2000 ng/mL with a limit of detection of 0.1 ng/mL for flunixin and 0.3 ng/mL for 5-hydroxy flunixin. Flunixin concentrations determined using the ELISAs were compared to concentrations derived from the same samples using LC-MS/MS analyses. Pharmacokinetic parameters of time versus concentration data from each analysis were estimated and compared. Differences (P flunixin analysis and that it would be difficult to differentiate routes of administration in healthy beef cattle based on the plasma elimination profile of flunixin after IV or SC administration.

  12. Accumulation of radioactivity in rat brain and peripheral tissues including salivary gland after intravenous administration of {sup 14}C-D-aspartic acid

    Energy Technology Data Exchange (ETDEWEB)

    Imai, Kazuhiro; Fukushima, Takeshi; Santa, Tomofumi; Homma, Hiroshi [Tokyo Univ. (Japan). Faculty of Pharmaceutical Sciences; Sugihara, Juko; Kodama, Hirohiko; Yoshikawa, Masayoshi

    1997-03-01

    After the intravenous administration of {sup 14}C-D-aspartic acid (Asp) into Sprague-Dawley rats (male, 7-week-old), the distribution and elimination of radioactivity was investigated by the whole body autoradiography. High radioactivities were detected in pineal gland, pituitary gland and salivary gland at 30 min after administration. The other tissues detected were liver, lung, adrenal gland, pancreas and spleen where D-Asp was reported to occur naturally. After 24 hr, the radioactivities were still detected at high levels in the pineal, pituitary and salivary glands. The data suggested the natural occurrence of D-Asp in salivary gland. After careful examination utilizing fluorescent derivatization and chiral separation by high-performance liquid chromatography, the presence of D-Asp was, for the first time, demonstrated in salivary gland in situ, the concentration of which was 7.85 {+-} 1.0 nmol/g. The administration of {sup 14}C-L-Asp was also carried out. The data suggested that D-Asp in the circulating blood is one of the sources of the tissue D-Asp. (author)

  13. PEGylated and Functionalized Aliphatic Polycarbonate Polyplex Nanoparticles for Intravenous Administration of HDAC5 siRNA in Cancer Therapy.

    Science.gov (United States)

    Frère, Antoine; Baroni, Alexandra; Hendrick, Elodie; Delvigne, Anne-Sophie; Orange, François; Peulen, Olivier; Dakwar, George R; Diricq, Jérôme; Dubois, Philippe; Evrard, Brigitte; Remaut, Katrien; Braeckmans, Kevin; De Smedt, Stefaan C; Laloy, Julie; Dogné, Jean-Michel; Feller, Georges; Mespouille, Laetitia; Mottet, Denis; Piel, Géraldine

    2017-01-25

    Guanidine and morpholine functionalized aliphatic polycarbonate polymers are able to deliver efficiently histone deacetylase 5 (HDAC5) siRNA into the cytoplasm of cancer cells in vitro leading to a decrease of cell proliferation were previously developed. To allow these biodegradable and biocompatible polyplex nanoparticles to overcome the extracellular barriers and be effective in vivo after an intravenous injection, polyethylene glycol chains (PEG750 or PEG2000) were grafted on the polymer structure. These nanoparticles showed an average size of about 150 nm and a slightly positive ζ-potential with complete siRNA complexation. Behavior of PEGylated and non-PEGylated polyplexes were investigated in the presence of serum, in terms of siRNA complexation (fluorescence correlation spectroscopy), size (dynamic light scattering and single-particle tracking), interaction with proteins (isothermal titration calorimetry) and cellular uptake. Surprisingly, both PEGylated and non-PEGylated formulations presented relatively good behavior in the presence of fetal bovine serum (FBS). Hemocompatibility tests showed no effect of these polyplexes on hemolysis and coagulation. In vivo biodistribution in mice was performed and showed a better siRNA accumulation at the tumor site for PEGylated polyplexes. However, cellular uptake in protein-rich conditions showed that PEGylated polyplex lost their ability to interact with biological membranes and enter into cells, showing the importance to perform in vitro investigations in physiological conditions closed to in vivo situation. In vitro, the efficiency of PEGylated nanoparticles decreases compared to non-PEGylated particles, leading to the loss of the antiproliferative effect on cancer cells.

  14. Single-dose pharmacokinetics of ampicillin/sulbactam (2:1) combination after intravenous administration to sheep and goats.

    Science.gov (United States)

    Carceles, C M; Espuny, A; Vicente, M S; Diaz, M S; Escudero, E

    1996-09-01

    The pharmacokinetic behaviour of a combination of ampicillin and sulbactam (2:1) in six sheep and six goats after single intravenous doses of 20 mg kg body weight-1 (13.33 mg kg-1 of ampicillin and 6.67 mg kg-1 of sulbactam) was investigated by using a high-performance liquid chromatographic method for determining plasma concentrations. The objective was to determine whether there are differences between sheep and goats in the disposition kinetics of ampicillin and sulbactam. The plasma concentration-time curves were analysed by compartmental pharmacokinetic and non-compartmental methods. The disposition curves for both drugs were best described by a biexponential equation (two-compartment open model) in both sheep and goats. The mean (SD) elimination half-lives of ampicillin were 0.32 (0.05) h in sheep and 0.32 (0.04) h in goats, and the half-lives of sulbactam were 0.74 (0.10) h and 0.79 (0.18) h in sheep and goats, respectively. The apparent volumes of distribution of ampicillin and sulbactam were similar in the two species. Mean (SD) body clearances of ampicillin were 0.69 (0.07) litre h-1 kg-1 in sheep and 0.72 (0.11) litre h-1 kg-1 in goats, and the body clearances of sulbactam were 0.38 (0.03) and 0.38 (0.07) litre h-1 kg-1 in sheep and goats, respectively. There were no significant differences between any of the pharmacokinetic parameters of ampicillin and sulbactam in the sheep and goats.

  15. Evaluation of clinical and paraclinical effects of intraosseous vs intravenous administration of propofol on general anesthesia in rabbits

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    Ramin Mazaheri-Khameneh

    2012-06-01

    Full Text Available This prospective study aimed to compare the intraosseous (IO and intravenous (IV effects of propofol on selected blood parameters and physiological variables during general anesthesia in rabbits. Thirty New Zealand White rabbits were studied. Six rabbits received IV propofol (group 1 and another 6 rabbits, were injected propofol intraosseously (Group 2 for 30 minutes (experimental groups. Rabbits of the third and fourth groups received IV and IO normal saline at the same volume given to the experimental groups, respectively. In the fifth group IO cannulation was performed but neither propofol nor normal saline were administered. Blood profiles were assayed before induction and after recovery of anesthesia. Heart and respiratory rates, rectal temperature, saturation of peripheral oxygen and mean arterial blood pressure were recorded. Heart rate increased significantly 1 to 5 minutes after induction of anesthesia in experimental groups (P < 0.05. Although mean arterial blood pressure decreased significantly from baseline, values remained above 60 mm Hg (P < 0.05. Respiratory rate decreased significantly in experimental groups, but remained higher in group 2 (P < 0.05. The lymphocyte count decreased significantly in group 1 (P < 0.05. The concentration of alkaline phosphatase in all rabbits, aspartate aminotransferase and gamma- glutamyl transferase in the first group and gamma-glutamyl transferase in the third group increased significantly (P < 0.05. Total bilirubin decreased significantly in group 2 (P < 0.05. All measured values remained within normal limits. Based on the least significant physiological, hematological and biochemical effects, the IO injection of propofol appears to be safe and suitable method of anesthesia in rabbits with limited vascular access.

  16. Repeated methamphetamine administration differentially alters fos expression in caudate-putamen patch and matrix compartments and nucleus accumbens.

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    Jakub P Jedynak

    Full Text Available BACKGROUND: The repeated administration of psychostimulant drugs produces a persistent and long-lasting increase ("sensitization" in their psychomotor effects, which is thought to be due to changes in the neural circuitry that mediate these behaviors. One index of neuronal activation used to identify brain regions altered by repeated exposure to drugs involves their ability to induce immediate early genes, such as c-fos. Numerous reports have demonstrated that past drug experience alters the ability of drugs to induce c-fos in the striatum, but very few have examined Fos protein expression in the two major compartments in the striatum--the so-called patch/striosome and matrix. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we used immunohistochemistry to investigate the effects of pretreatment with methamphetamine on the ability of a subsequent methamphetamine challenge to induce Fos protein expression in the patch and matrix compartments of the dorsolateral and dorsomedial caudate-putamen and in the ventral striatum (nucleus accumbens. Animals pretreated with methamphetamine developed robust psychomotor sensitization. A methamphetamine challenge increased the number of Fos-positive cells in all areas of the dorsal and ventral striatum. However, methamphetamine challenge induced Fos expression in more cells in the patch than in the matrix compartment in the dorsolateral and dorsomedial caudate-putamen. Furthermore, past experience with methamphetamine increased the number of methamphetamine-induced Fos positive cells in the patch compartment of the dorsal caudate putamen, but not in the matrix or in the core or shell of the nucleus accumbens. CONCLUSIONS/SIGNIFICANCE: These data suggest that drug-induced alterations in the patch compartment of the dorsal caudate-putamen may preferentially contribute to some of the enduring changes in brain activity and behavior produced by repeated treatment with methamphetamine.

  17. Stability study of docetaxel solution (0.9%, saline) using Non-PVC and PVC tubes for intravenous administration

    OpenAIRE

    Park, Kang Hoon; Chung, Dong June

    2015-01-01

    Background Di-2-ethylhexyl phthalate (DEHP) are added to poly(vinyl chloride)(PVC) infusion tubes as a plasticizer to ensure tube flexibility. In addition to previously reported disadvantages of DEHP, released DEHP molecules from PVC tubes can easily interact with surfactants in anticancer drug solutions (i.e., polysorbate 80 for Taxotere®-Inj) and reduce the solubility of docetaxel in aqueous solution during anticancer drug administration. Results In this study, we investigated the in vitro ...

  18. Marked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxy-cholecalciferol in uremic patients.

    OpenAIRE

    Slatopolsky, E.; Weerts, C; Thielan, J; van der Horst, R.; Harter, H; Martin, K.J.

    1984-01-01

    Current evidence suggests that administration of 1,25(OH)2D3 to patients with chronic renal insufficiency results in suppression of secondary hyperparathyroidism only if hypercalcemia occurs. However, since the parathyroid glands possess specific receptors for 1,25(OH)2D3 and a calcium binding protein, there is considerable interest in a possible direct effect of 1,25(OH)2D3 on parathyroid hormone (PTH) secretion independent of changes in serum calcium. Recent findings indicate substantial de...

  19. Evaluation of plasma diazepam and nordiazepam concentrations following administration of diazepam intravenously or via suppository per rectum in dogs.

    Science.gov (United States)

    Probst, Curtis W; Thomas, William B; Moyers, Tamberlyn D; Martin, Tomas; Cox, Sherry

    2013-04-01

    To evaluate the pharmacokinetics of diazepam administered per rectum via compounded (ie, not commercially available) suppositories and determine whether a dose of 2 mg/kg in this formulation would result in plasma concentrations shown to be effective for control of status epilepticus or cluster seizures (ie, 150 to 300 ng/mL) in dogs within a clinically useful interval (10 to 15 minutes). 6 healthy mixed-breed dogs. Dogs were randomly assigned to 2 groups of 3 dogs each in a crossover-design study. Diazepam (2 mg/kg) was administered IV or via suppository per rectum, and blood samples were collected at predetermined time points. Following a 6- or 7-day washout period, each group received the alternate treatment. Plasma concentrations of diazepam and nordiazepam were analyzed via reversed phase high-performance liquid chromatography. Plasma concentrations of diazepam and nordiazepam exceeded the targeted range ≤ 3 minutes after IV administration in all dogs. After suppository administration, targeted concentrations of diazepam were not detected in any dogs, and targeted concentrations of nordiazepam were detected after 90 minutes (n = 2 dogs) or 120 minutes (3) or were not achieved (1). On the basis of these results, administration of 2 mg of diazepam/kg via the compounded suppositories used in the present study cannot be recommended for emergency treatment of seizures in dogs.

  20. Pain management in emergency department: intravenous morphine vs. intravenous acetaminophen

    Directory of Open Access Journals (Sweden)

    Morteza Talebi Doluee

    2015-01-01

    Full Text Available Pain is the most common complaint in emergency department and there are several methods for its control. Among them, pharmaceutical methods are the most effective. Although intravenous morphine has been the most common choice for several years, it has some adverse effects. There are many researches about intravenous acetaminophen as an analgesic agent and it appears that it has good analgesic effects for various types of pain. We searched some electronic resources for clinical trials comparing analgesic effects of intravenous acetaminophen vs. intravenous morphine for acute pain treatment in emergency setting.In two clinical trials, the analgesic effect of intravenous acetaminophen has been compared with intravenous morphine for renal colic. The results revealed no significant difference between analgesic effects of two medications. Another clinical trial revealed that intravenous acetaminophen has acceptable analgesic effects on the post-cesarean section pain when combined with other analgesic medications. One study revealed that administration of intravenous acetaminophen compared to placebo before hysterectomy decreased consumption of morphine via patient-controlled analgesia pump and decreased the side effects. Similarly, another study revealed that the infusion of intravenous acetaminophen vs. placebo after orthopedic surgery decreased the consumption of morphine after the surgery. A clinical trial revealed intravenous acetaminophen provided a level of analgesia comparable to intravenous morphine in isolated limb trauma, while causing less side effects than morphine.It appears that intravenous acetaminophen has good analgesic effects for visceral, traumatic and postoperative pains compare with intravenous morphine.

  1. Region-specific induction of deltaFosB by repeated administration of typical versus atypical antipsychotic drugs.

    Science.gov (United States)

    Atkins, J B; Chlan-Fourney, J; Nye, H E; Hiroi, N; Carlezon, W A; Nestler, E J

    1999-08-01

    Whereas acute administration of many types of stimuli induces c-Fos and related proteins in brain, recent work has shown that chronic perturbations cause the region-specific accumulation of novel Fos-like proteins of 35-37 kD. These proteins, termed chronic FRAs (Fos-related antigens), have recently been shown to be isoforms of DeltaFosB, which accumulate in brain due to their enhanced stability. In the present study, we sought to extend earlier findings that documented the effects of acute administration of antipsychotic drugs (APDs) on induction of Fos-like proteins by investigating the ability of typical and aytpical APDs, after chronic administration, to induce these DeltaFosB isoforms in several brain regions implicated in the clinical actions of these agents. By Western blotting we found that chronic administration of the typical APD, haloperidol, dramatically induces DeltaFosB in caudate-putamen (CP), a brain region associated with the extrapyramidal side effects of this drug. A smaller induction was seen in the nucleus accumbens (NAc) and prefrontal cortex (PFC), brain regions associated with the antipsychotic effects of the drug. In contrast, chronic administration of the prototype atypical APD clozapine failed to significantly increase levels of DeltaFosB in any of the three brain regions, and even tended to reduce DeltaFosB levels in the NAc. Two putative atypical APDs, risperidone and olanzapine, produced small but still significant increases in the levels of DeltaFosB in CP, but not NAc or PFC. Studies with selective receptor antagonists suggested that induction of DeltaFosB in CP and NAc is most dependent on antagonism of D2-D3 dopamine receptors, with antagonism of D1-like receptors most involved in the PFC. Immunohistochemical analysis confirmed the greater induction of DeltaFosB in CP by typical versus atypical APDs, with no significant induction seen in PFC with either class of APD. Together, these findings demonstrate that repeated administration

  2. Effects of intravenous administration of perzinfotel, fentanyl, and a combination of both drugs on the minimum alveolar concentration of isoflurane in dogs.

    Science.gov (United States)

    Ueyama, Yukie; Lerche, Phillip; Eppler, C Mark; Muir, William W

    2009-12-01

    OBJECTIVE-To determine the effects of IV administration of perzinfotel and a perzinfotel-fentanyl combination on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS-6 healthy sexually intact Beagles (3 males and 3 females). PROCEDURES-All dogs were instrumented with a telemetry device for continuous monitoring of heart rate, arterial blood pressure, and core body temperature (at a femoral artery). Dogs were anesthetized with propofol (6 mg/kg, IV) and isoflurane. Isoflurane MAC values were determined in 3 experiments in each dog, separated by at least 7 days, before (baseline) and after the following treatments: no treatment (anesthetic only), perzinfotel (20 mg/kg, IV), fentanyl (5 microg/kg bolus, IV, followed by a continuous IV infusion at 0.15 microg/kg/min), and a fentanyl-perzinfotel combination (20 mg of perzinfotel/kg, IV, plus the fentanyl infusion). Bispectral index and oxygen saturation as measured by pulse oximetry were also monitored throughout anesthesia. RESULTS-Without treatment, the mean +/- SD isoflurane MAC for all 6 dogs was 1.41 +/- 0.10%. Baseline MAC was 1.42 +/- 0.08%. Intravenous administration of perzinfotel, fentanyl, and the perzinfotel-fentanyl combination significantly decreased the MAC by 39%, 35%, and 66%, respectively. Perzinfotel and perzinfotel-fentanyl administration yielded significant increases in the bispectral index. Mean, systolic, and diastolic arterial blood pressures significantly increased from baseline values when perzinfotel was administered. Systolic arterial blood pressure significantly increased from the baseline value when perzinfotel-fentanyl was administered. No adverse effects were detected. CONCLUSIONS AND CLINICAL RELEVANCE-IV administration of perzinfotel, fentanyl, or a perzinfotel-fentanyl combination reduced isoflurane MAC in dogs and increased arterial blood pressure.

  3. Population Pharmacokinetics of High-dose Methotrexate After Intravenous Administration in Chinese Osteosarcoma Patients from a Single Institution

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Qing Zhang; Xiaohuang Tian; Haitao Zhao; Wei Lu; Jiancun Zhen; Xiaohui Niu

    2015-01-01

    Background:High-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is the gold standard therapy in the treatment of osteosarcoma.The plasma concentration of MTX is closely related to efficacy and toxicity.There are large individual differences.Many authors have described the pharmacokinetic (PK) profile of MTX regarding osteosarcoma under a variety of circumstances.However,no data concerning Chinese osteosarcoma patient PKs using the nonlinear mixed effects models (NONMEM) have been previously reported.The goals of this study were to establish the population pharmacokinetics (PPK) of HD-MTX treatment in Chinese osteosarcoma patients,and to explore the influence of patient covariates and between-occasion variability on drug disposition.Methods:An intravenous HD-MTX solution (10 g/m2) was given 274 times to 148 osteosarcoma patients.MTX plasma concentrations were measured at 0,6,12,24,48 and 72 h after commencement of the infusion,and the fluorescence polarization immunoassay was used to determine MTX plasma concentrations.The PPK model and parameters were estimated using NONMEM software.The effects of fixed-effect factors were evaluated,and the final regression model was obtained.Results:The following population parameters were obtained using a two-compartment model:CL1 (clearance of central compartment):(CL1)i =CL1 Tv × [1-θCt-MTXNUM × MTXNUM] × [1-θCL1-CrCl1 × (CrCl1-1.89)] × eηCLi (L/h).V1 (central volume):(V11)i =V1TV × eηV1i (L).CL2 (clearance of peripheral compartment):(CL2)i =CL2TV × [1-θCL2-BODYAREA × (bodyarea-1.62)] × eηCL2i (L/h).V2 (peripheral compartment):(V2)i =V2Tv × [1-θV2-bodyarea × (bodyarea-1.62)] × eηV2i (L).The PPK parameters (RSD%) were CL1,V1,CL2 and V2 with values of 6.20 L/h (8.48%),19.6 L (extremely small),0.0172 L/h (50.9%) and 0.515 L (39.1%),respectively.Creatinine clearance and the number of methotrexate chemotherapy cycles before MTX infusion had a significant effect on the CL 1,and body

  4. Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice.

    Science.gov (United States)

    Schiavon, Angélica Pupin; Bonato, Jéssica Mendes; Milani, Humberto; Guimarães, Francisco Silveira; Weffort de Oliveira, Rúbia Maria

    2016-01-04

    Therapeutic effects of antidepressants and atypical antipsychotics may arise partially from their ability to stimulate neurogenesis. Cannabidiol (CBD), a phytocannabinoid present in Cannabis sativa, presents anxiolytic- and antipsychotic-like effects in preclinical and clinical settings. Anxiolytic-like effects of repeated CBD were shown in chronically stressed animals and these effects were parallel with increased hippocampal neurogenesis. However, antidepressant-like effects of repeated CBD administration in non-stressed animals have been scarcely reported. Here we investigated the behavioral consequences of single or repeated CBD administration in non-stressed animals. We also determined the effects of CBD on cell proliferation and neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ). Single CBD 3mg/kg administration resulted in anxiolytic-like effect in mice submitted to the elevated plus maze (EPM). In the tail suspension test (TST), single or repeated CBD administration reduced immobility time, an effect that was comparable to those of imipramine (20 mg/kg). Moreover, repeated CBD administration at a lower dose (3 mg/kg) increased cell proliferation and neurogenesis, as seen by an increased number of Ki-67-, BrdU- and doublecortin (DCX)-positive cells in both in DG and SVZ. Despite its antidepressant-like effects in the TST, repeated CBD administration at a higher dose (30 mg/kg) decreased cell proliferation and neurogenesis in the hippocampal DG and SVZ. Our findings show a dissociation between behavioral and proliferative effects of repeated CBD and suggest that the antidepressant-like effects of CBD may occur independently of adult neurogenesis in non-stressed Swiss mice.

  5. Induction of systemic TH1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CPG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist.

    Science.gov (United States)

    Krieg, Arthur M; Efler, Susan M; Wittpoth, Michael; Al Adhami, Mohammed J; Davis, Heather L

    2004-01-01

    Subcutaneous injection of normal human volunteers with a B-class CpG oligodeoxynucleotide (ODN) TLR9 agonist, CPG 7909, induced a TH1-like pattern of systemic innate immune activation manifested by expression of IL-6, IL-12p40, IFN-alpha, and IFN-inducible chemokines. Serum IP-10 was found to be the most sensitive assay for subcutaneous CPG 7909 stimulation; its level was significantly increased in all subjects at all dose levels, including the lowest tested dose of just 0.0025 mg/kg. This pattern of chemokine and cytokine induction was markedly different from that previously reported to be induced by TLR9 stimulation in rodents, most likely reflecting species-specific differences in the cell types expressing TLR9. Subcutaneous CPG 7909 injection induced transient shifts in blood neutrophils, lymphocytes, and monocytes, consistent with the increased chemokine expression. Levels of acute phase reactants such as C-reactive protein were also increased. A second subcutaneous CPG 7909 injection administered 2 weeks after the first elicited similar immune responses, showing little or no tolerance to the effects of repeated in vivo TLR9 stimulation. Subjects developed dose-dependent transient injection site reactions and flu-like symptoms but otherwise tolerated injection well, with no evidence of organ toxicity or systemic autoimmunity. The activation of innate immunity was dependent on the route of ODN administration, since intravenous injection caused no such effects. These studies indicate that in vivo activation of TLR9 by subcutaneous administration of CPG 7909 could be a well-tolerated immunotherapeutic approach for induction of TH1 innate immune activation.

  6. Absolute bioavailability of evacetrapib in healthy subjects determined by simultaneous administration of oral evacetrapib and intravenous [(13) C8 ]-evacetrapib as a tracer.

    Science.gov (United States)

    Cannady, Ellen A; Aburub, Aktham; Ward, Chris; Hinds, Chris; Czeskis, Boris; Ruterbories, Kenneth; Suico, Jeffrey G; Royalty, Jane; Ortega, Demetrio; Pack, Brian W; Begum, Syeda L; Annes, William F; Lin, Qun; Small, David S

    2016-05-30

    This open-label, single-period study in healthy subjects estimated evacetrapib absolute bioavailability following simultaneous administration of a 130-mg evacetrapib oral dose and 4-h intravenous (IV) infusion of 175 µg [(13) C8 ]-evacetrapib as a tracer. Plasma samples collected through 168 h were analyzed for evacetrapib and [(13) C8 ]-evacetrapib using high-performance liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameter estimates following oral and IV doses, including area under the concentration-time curve (AUC) from zero to infinity (AUC[0-∞]) and to the last measureable concentration (AUC[0-tlast ]), were calculated. Bioavailability was calculated as the ratio of least-squares geometric mean of dose-normalized AUC (oral : IV) and corresponding 90% confidence interval (CI). Bioavailability of evacetrapib was 44.8% (90% CI: 42.2-47.6%) for AUC(0-∞) and 44.3% (90% CI: 41.8-46.9%) for AUC(0-tlast ). Evacetrapib was well tolerated with no reports of clinically significant safety assessment findings. This is among the first studies to estimate absolute bioavailability using simultaneous administration of an unlabeled oral dose with a (13) C-labeled IV microdose tracer at about 1/1000(th) the oral dose, with measurement in the pg/mL range. This approach is beneficial for poorly soluble drugs, does not require additional toxicology studies, does not change oral dose pharmacokinetics, and ultimately gives researchers another tool to evaluate absolute bioavailability.

  7. Simultaneous determination and pharmacokinetic study of four phenolic acids in rat plasma using UFLC-MS/MS after intravenous administration of salvianolic acid for injection.

    Science.gov (United States)

    Xie, Xiuman; Miao, Jingzhuo; Sun, Wanyang; Huang, Jingyi; Li, Dongxiang; Li, Shuming; Tong, Ling; Sun, Guoxiang

    2017-02-05

    A simple, sensitive and selective ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method was established for simultaneous determination and pharmacokinetic study of rosmarinic acid (RA), salvianolic acid D (Sal D), lithospermic acid (LA) and salvianolic acid B (Sal B) in rat plasma after intravenous administration of salvianolic acid for injection (SAFI). Three doses of administration, containing 14, 28 and 56mg/kg, were investigated in this study. Plasma samples were pretreated using protein precipitation (PP) with pre-cooled acetonitrile. Chromatographic separation was achieved on a CORTECS™ UPLC C18 column (1.6μm, 2.1×100mm) with a mobile phase composed of 0.1% formic acid aqueous (V/V) and 0.1% formic acid acetonitrile (V/V). Analytes were detected using electrospray ionization (ESI) source in negative ionization mode and quantified in multiple reaction monitoring (MRM) mode. The validated method is stable and reliable. No significant difference of half lives (t1/2) of four analytes at three doses was observed. Area under the curve (AUC0-∞) and peak concentration (Cmax) of the four analytes demonstrated a linear increase in across the doses with the linear correlation r of each analyte at three doses were greater than 0.95. It indicated that the pharmacokinetic behavior of SAFI is positively related to dose at the range of 14-56mg/kg.

  8. Pre-surgical mapping of primary motor cortex by functional MRI at 3 T: effects of intravenous administration of Gd-DTPA

    Energy Technology Data Exchange (ETDEWEB)

    Naganawa, Shinji; Nihashi, Takashi; Fukatsu, Hiroshi; Ishigaki, Takeo [Department of Radiology, Nagoya University School of Medicine, 65 Tsurumai-cho, Shouwa-ku, 466-8550, Nagoya (Japan); Aoki, Ikuo [Toshiba Medical Systems Company, Tokyo (Japan)

    2004-01-01

    The functional magnetic resonance imaging (fMRI) is often performed at the end of a routine MRI examination during which, dependent on the clinical indication, contrast agent has been administered; however, the effects of Gd-DTPA injection on the results of blood oxygenation level dependent (BOLD)-fMRI remain unknown. The present study was conducted to investigate the effects of the intravenous administration of Gd-DTPA on the results of pre-surgical localization of the primary motor cortex by BOLD-fMRI at 3 T. Eight normal subjects were included in this study. After the anatomical scans, pre- and post-contrast fMRI scanning was performed. The number of significantly activated voxels and the mean percentage signal change were compared. The mean number of significantly activated voxels was 115.0{+-}27.0 in pre-contrast runs and 90.8{+-}27.1 in post-contrast runs (mean value of all 8 volunteers{+-}standard deviation; p<0.05). The mean mean percentage signal change was 4.07{+-}0.39 in pre-contrast runs and 3.86{+-}1.91 in post-contrast runs (p=0.16). Pre-surgical localization of the motor area by BOLD-fMRI should be performed before the administration of Gd contrast material. (orig.)

  9. Disposition of human recombinant lubricin in naive rats and in a rat model of post-traumatic arthritis after intra-articular or intravenous administration.

    Science.gov (United States)

    Vugmeyster, Yulia; Wang, Qin; Xu, Xin; Harrold, John; Daugusta, Daren; Li, Jian; Zollner, Richard; Flannery, Carl R; Rivera-Bermúdez, Moisés A

    2012-03-01

    We have recently demonstrated that intra-articular (IA) administration of human recombinant lubricin, LUB:1, significantly inhibited cartilage degeneration and pain in the rat meniscal tear model of post-traumatic arthritis. In this report, we show that after a single IA injection to naïve rats and rats that underwent unilateral meniscal tear, [(125)I]LUB:1 had a tri-phasic disposition profile, with the alpha, beta, and gamma half-life estimates of 4.5 h, 1.5 days, and 2.1 weeks, respectively. We hypothesize that the terminal phase kinetics was related to [(125)I]LUB:1 binding to its ligands. [(125)I]LUB:1 was detected on articular cartilage surfaces as long as 28 days after single IA injection. Micro-autoradiography analysis suggested that [(125)I]LUB:1 tended to localize to damaged joint surfaces in rats with meniscal tear. After a single intravenous (IV) dose to rats, [(125)I]LUB:1 was eliminated rapidly from the systemic circulation, with a mean total body clearance of 154 mL/h/kg and a mean elimination half-life (t (1/2)) of 6.7 h. Overall, LUB:1 has met a desired disposition profile of a potential therapeutic intended for an IA administration: target tissue (knee) retention and fast elimination from the systemic circulation after a single IA or IV dose.

  10. Intravenous administration of equine-derived whole IgG antivenom does not induce early adverse reactions in non-envenomed horses and cows.

    Science.gov (United States)

    Estrada, Ricardo; Herrera, María; Segura, Alvaro; Araya, Javier; Boschini, Carlos; Gutiérrez, José María; León, Guillermo

    2010-11-01

    Administration of antivenoms to treat snakebite envenomings has the potential risk of inducing early adverse reactions. The mechanisms involved in these reactions are unclear. In this study, polyspecific antivenom consisting of whole IgG purified from equine plasma by caprylic acid precipitation was administered intravenously to non-envenomed horses (n = 47) and cows (n = 20) at a dose of 0.4 mL/kg. It has been reported that, in humans, this formulation (administered at a dose of 0.4 mL/kg) induces mild noticeable early adverse reactions, such as fever, vomiting, diarrhea, urticaria, generalized rash, tachypnea or tachycardia, in about 15-20% of the patients. Unexpectedly, none of the animals receiving antivenom in our study showed any evidence of early adverse reaction. Moreover, no late adverse reactions, i.e. serum sickness, were observed during 40 days after antivenom administration. Unlike studies performed in envenomed humans, our present results were obtained in a group of non-envenomed individuals. It is concluded that, in addition to the physicochemical characteristics of the formulation, other unknown factors must determine the occurrence of adverse reactions in snakebite envenomed humans treated with equine-derived antivenoms.

  11. Comparative study of amino acid, ammonia and pancreatic hormone levels in the blood of cirrhotic patients following intragastric and intravenous administration of a branched-chain amino acid-enriched solution.

    Directory of Open Access Journals (Sweden)

    Watanabe,Akiharu

    1983-10-01

    Full Text Available The blood levels of amino acids, ammonia and pancreatic hormones following the intragastric and intravenous administration of a branched-chain amino acid (BCAA-enriched solution were comparatively investigated in control subjects and patients with liver cirrhosis. There was no essential difference in the time course of serum amino acid and blood ammonia levels between the intragastric and intravenous infusions. Elevation of serum insulin concentrations in cirrhotic patients was significant only immediately after the administration through the enteral route. However, plasma glucagon levels increased similarly when the BCAA-enriched solution was administered through either route. The results indicate that both enteral and intravenous infusions will have similar therapeutic effects on the impaired protein metabolism in cirrhotic patients with protein-calorie malnutrition.

  12. Early Effects of Single and Low-Frequency Repeated Administration of Teriparatide, hPTH(1-34), on Bone Formation and Resorption in Ovariectomized Rats.

    Science.gov (United States)

    Isogai, Yukihiro; Takao-Kawabata, Ryoko; Takakura, Aya; Sugimoto, Emika; Nakazono, Osamu; Ikegaki, Ichiro; Kuriyama, Hiroshi; Ishizuya, Toshinori

    2015-10-01

    Intermittent repeated administration of teriparatide (TPTD) has potent anabolic effects on bones in vivo. However, TPTD has both anabolic and catabolic effects on osteoblasts in vitro, and the mechanisms underlying its promotion of bone formation are unclear. This study aimed to elucidate the time-dependent changes in bone formation and resorption by examining changes in bone turnover markers and bone tissue over time after TPTD administration with low frequency in ovariectomized rats. The amount of serum osteocalcin, a bone formation marker, was transiently reduced after single TPTD administration, but increased thereafter, remaining increased for several days. In contrast, the amount of excreted urinary C-telopeptide, a bone resorption marker, increased transiently after single TPTD administration, and subsequently returned to control levels on the day after administration. Tissue histomorphometric analyses conducted 8 h after administration showed no changes in bone formation or bone resorption parameters. However, at 48 h, the bone formation parameters OS/BS and Ob.S/BS were increased, while the bone resorption parameter ES/BS was decreased. After repeated TPTD administration for 4 weeks, OS/BS, Ob.S/BS, and MS/BS increased, while Oc.S/BS decreased. Serum osteocalcin at 4 weeks after repeated administration was significantly correlated with OS/BS and Ob.S/BS. These present findings indicate that TPTD has dual, time-dependent effects on bone resorption and bone formation. Immediately after single administration, there was transient promotion of bone resorption and suppression of bone formation. However, sustained stimulation of bone formation occurred thereafter. Furthermore, these data suggest that this sustained bone formation led to anabolic effects with repeated TPTD administration.

  13. ENHANCED LIVER DELIVERY AND SUSTAINED RELEASE OF CURCUMIN WITH DRUG LOADED NANOPARTICLES AFTER INTRAVENOUS ADMINISTRATION IN RATS

    Directory of Open Access Journals (Sweden)

    SURESH K, BONEPALLY REDDY, JITHAN A

    2013-09-01

    Full Text Available Liver targeting drug delivery systems can improve thedelivery of several drugs useful in the treatment of liverdisorders such as cirrhosis and liver cancer. Theobjective of this study was to prepare the biodegradablenanoparticles containing curcumin, a well-knownhepatoprotective agent and further to evaluate the livertargetability and sustained release of curcumin with thedeveloped nanoformulation. Curcumin nanoparticleswere prepared by double emulsion (w/o/w solventevaporation method using different drug polymer ratios.Poly-ε-caprolactone was used in the preparation. Theprepared formulations were evaluated for particles size,surface potential, entrapment efficiency, in vitro release,drug polymer interaction. Four different formulationsCNP1, CNP2, CNP3 and CNP4 were prepared.Optimized formulation (CNP3 was evaluated forpharmacokinetics and hepatoprotective activity in CCl4induced liver toxicity model after i.v. administration.Optimized formulation was selected based on the size,entrapment efficiency and release characteristics.Curcumin i.v. solution and oral suspension form wereused as the reference. Particle size of all formulationswas in the range of 300-470 nm and the entrapmentefficiencies were in the range of 75-85 %. Drug releasefrom the nanoparticles was sustained both in vitro and invivo. Nanoparticle formulation tested in vivodemonstrated better pharmacokinetics andpharmacodynamics compared to the reference. Druglevels in the liver were significantly higher withnanoparticular formulation. Thus, this studysuccessfully prepared a nanoparticular formulationcontaining curcumin with polycaprolactone as thepolymer. With the developed formulation better livertargetability was achieved.

  14. Elucidation of arctigenin pharmacokinetics after intravenous and oral administrations in rats: integration of in vitro and in vivo findings via semi-mechanistic pharmacokinetic modeling.

    Science.gov (United States)

    Gao, Qiong; Zhang, Yufeng; Wo, Siukwan; Zuo, Zhong

    2014-11-01

    Although arctigenin (AR) has attracted substantial research interests due to its promising and diverse therapeutic effects, studies regarding its biotransformation were limited. The current study aims to provide information regarding the pharmacokinetic properties of AR via various in vitro and in vivo experiments as well as semi-mechanistic pharmacokinetic modeling. Our in vitro rat microsome incubation studies revealed that glucuronidation was the main intestinal and liver metabolic pathway of AR, which occurred with V max, K m, and Clint of 47.5 ± 3.4 nmol/min/mg, 204 ± 22 μM, and 233 ± 9 μl/min/mg with intestinal microsomes and 2.92 ± 0.07 nmol/min/mg, 22.7 ± 1.2 μM, and 129 ± 4 μl/min/mg with liver microsomes, respectively. In addition, demethylation and hydrolysis of AR occurred with liver microsomes but not with intestinal microsomes. In vitro incubation of AR and its metabolites in intestinal content demonstrated that glucuronides of AR excreted in bile could be further hydrolyzed back to the parent compound, suggesting its potential enterohepatic circulation. Furthermore, rapid formation followed by fast elimination of arctigenic acid (AA) and arctigenin-4'-O-glucuronide (AG) was observed after both intravenous (IV) and oral administrations of AR in rats. Linear pharmacokinetics was observed at three different doses for AR, AA, and AG after IV administration of AR (0.48-2.4 mg/kg, r (2) > 0.99). Finally, an integrated semi-mechanistic pharmacokinetic model using in vitro enzyme kinetic and in vivo pharmacokinetic parameters was successfully developed to describe plasma concentrations of AR, AA, and AG after both IV and oral administration of AR at all tested doses.

  15. Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1α

    Directory of Open Access Journals (Sweden)

    Tayra Judith

    2010-04-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1α (SDF-1α is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1α were explored. 6-hydroxydopamine (6-OHDA, 20 μg was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 × 107 cells, respectively or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1α were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL staining. Results Rats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc compared to that of control rats. In the in vitro study, SDF-1α treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups. Conclusions Consequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1α. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.

  16. NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala.

    Science.gov (United States)

    Kenny, Paul J; Chartoff, Elena; Roberto, Marisa; Carlezon, William A; Markou, Athina

    2009-01-01

    Nicotine is considered an important component of tobacco responsible for the smoking habit in humans. Nicotine increases glutamate-mediated transmission throughout brain reward circuitries. This action of nicotine could potentially contribute to its intrinsic rewarding and reward-enhancing properties, which motivate consumption of the drug. Here we show that the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.5-2.5 mg per kg) abolished nicotine-enhanced brain reward function, reflected in blockade of the lowering of intracranial self-stimulation (ICSS) thresholds usually observed after experimenter-administered (0.25 mg per kg) or intravenously self-administered (0.03 mg per kg per infusion) nicotine injections. The highest LY235959 dose (5 mg per kg) tested reversed the hedonic valence of nicotine from positive to negative, reflected in nicotine-induced elevations of ICSS thresholds. LY235959 doses that reversed nicotine-induced lowering of ICSS thresholds also markedly decreased nicotine self-administration without altering responding for food reinforcement, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist NBQX had no effects on nicotine intake. In addition, nicotine self-administration upregulated NMDA receptor subunit expression in the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA), suggesting important interactions between nicotine and the NMDA receptor. Furthermore, nicotine (1 microM) increased NMDA receptor-mediated excitatory postsynaptic currents in rat CeA slices, similar to its previously described effects in the VTA. Finally, infusion of LY235959 (0.1-10 ng per side) into the CeA or VTA decreased nicotine self-administration. Taken together, these data suggest that NMDA receptors, including those in the CeA and VTA, gate the magnitude and valence of the effects of nicotine on brain reward systems, thereby regulating motivation to consume the drug.

  17. Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Quattrocchi, Emilia; Ostergaard, Mikkel; Taylor, Peter C.

    2016-01-01

    OBJECTIVES: To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. METHODS: Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab...... retreatment (700 mg X 2 intravenous infusions two weeks apart) ≥24 weeks following the first course and ≥16 weeks following further courses. Retreatment required evidence of clinical response followed by disease relapse. These studies were prematurely terminated by the sponsor to refocus development...... was 463, 182 and 175 patient-years, respectively. Mean time between courses was 17-47 weeks. Ofatumumab induced a profound depletion of peripheral B-lymphocytes. Retreated patients derived benefit based on improvement in DAS28. Adverse events were reported for 93% (226/243), 91% (134/148) and 76% (70...

  18. [Intravenous Sedation and Repeated "the Same Day General Anesthesia" for a School-age Boy with Dandy-Walker Syndrome and Dentinogenesis].

    Science.gov (United States)

    Hitosugi, Takashi; Tsukamoto, Masanori; Fujiwara, Shigeki; Yokoyama, Takeshi

    2016-03-01

    Dandy-Walker syndrome (DWS) is characterized by perfect or partial defect of the cerebellum vermis and cystic dilatation of the posterior fossa communicating with the fourth ventricle. Common clinical signs are mental retardation, cerebellar ataxia, and those of increased intracranial pressure (ICP). Associated congenital anomalies are craniofacial, cardiac, renal, and skeletal abnormalities. We experienced a case of intravenous sedation and six times of "the same day" general anesthesia for a school-aged boy (10-13 years old) with DWS and hypodentinogenesis. The patient underwent an examination and dental treatments. We had to pay attention to airway management tracheal tube selection and control of ICP. In addition, we should prevent tooth injuries through mishaps during tracheal intubations, since all-tooth-hypoplasia with fragile dental crowns was strongly suggested in this case. Detailed postoperative care is also required for general anesthesia afflicted with DWS.

  19. Use of polyglycerol (PG), instead of polyethylene glycol (PEG), prevents induction of the accelerated blood clearance phenomenon against long-circulating liposomes upon repeated administration.

    Science.gov (United States)

    Abu Lila, Amr S; Nawata, Kosuke; Shimizu, Taro; Ishida, Tatsuhiro; Kiwada, Hiroshi

    2013-11-01

    The accelerated blood clearance (ABC) phenomenon accounts for the rapid systemic clearance of PEGylated nanocarriers upon repeated administrations. IgM production against the polyethylene glycol (PEG) coating in PEGylated liposomes is now known to be responsible for such unexpected pharmacokinetical alterations. The ABC phenomenon poses a remarkable clinical challenge by reducing the therapeutic efficacy of encapsulated drugs and causing harmful effects due to the altered tissue distribution pattern of the drugs. In this study, we investigated the in vivo performance of liposomes modified with polyglycerol (PG) upon repeated injection, and the in vivo therapeutic efficacy of such liposomes when they encapsulated a cytotoxic agent, doxorubicin (DXR). Repeated injection of PEG-coated liposomes in rats induced the ABC phenomenon, while repeated injection of PG-coated liposomes did not. In addition, DXR-containing PG-coated liposomes showed antitumor activity that was superior to that of free DXR and similar to that of DXR-containing PEG-coated liposomes upon repeated administration. These results indicate that polyglycerol (PG) might represent a promising alternative to PEG via enhancing the in vivo performance of liposomes by not eliciting the ABC phenomenon upon repeated administration.

  20. Intravenous thrombolysis on early recurrent cardioembolic stroke: 'Dr Jekyll' or 'Mr Hyde'?

    Science.gov (United States)

    Cappellari, Manuel; Tomelleri, Giampaolo; Carletti, Monica; Bovi, Paolo; Moretto, Giuseppe

    2012-01-01

    Early recurrent cardioembolic stroke on the previously unaffected side has very rarely been reported during or after intravenous recombinant tissue plasminogen activator for acute ischemic stroke. For these cases, thrombolysis guidelines lack any clear recommendation. We report two cases of thrombolysed stroke patients, with paroxysmal atrial fibrillation but normal sinus rhythm on admission, who respectively developed recurrent ischemic stroke within few hours after complete improvement and during intravenous recombinant tissue plasminogen activator infusion. Intravenous thrombolysis was successfully repeated after echocardiographic evidence of left appendage thrombus in the first case and discontinued before complete administration in the second.

  1. Toxicokinetics of the nerve agent (+/-)-VX in anesthetized and atropinized hairless guinea pigs and marmosets after intravenous and percutaneous administration.

    Science.gov (United States)

    van der Schans, Marcel J; Lander, Brenda J; van der Wiel, Herma; Langenberg, Jan P; Benschop, Hendrik P

    2003-08-15

    In continuation of our investigations on the toxicokinetics of the volatile nerve agents C(+/-)P(+/-)-soman and (+/-)-sarin, we now report on the toxicokinetics of the rather nonvolatile agent (+/-)-VX. A validated method was developed to determine blood levels of (+/-)-VX by means of achiral gas chromatography at blood levels > or =10 pg/ml. The ratio of the two enantiomers of VX in blood could be measured at levels > or =1 ng/ml by using chiral HPLC in combination with off-line gas chromatographic analysis. In order to obtain basic information on the toxicokinetics of (+/-)-VX, i.e., under conditions of 100% bioavailability, the blood levels of this agent were measured in hairless guinea pigs at iv doses corresponding with 1 and 2 LD50. The derived AUCs indicate a reasonable linearity of the toxicokinetics with dose. Also, the toxicokinetics in marmoset primates was studied at an absolute iv dose corresponding with 1 LD50 in the hairless guinea pig which led to approximately the same levels of (+/-)-VX in blood as observed at 2 LD50 in the hairless guinea pig. Finally, the toxicokinetics of (+/-)-VX were measured in hairless guinea pigs via the most relevant porte d' entrée for this agent, which is the percutaneous route at a dose corresponding with 1 LD50 (pc). Large variations were observed between individual animals in the rate of penetration of (+/-)-VX and in concomitant progression of AChE inhibition in blood of these animals. Blood levels of (+/-)-VX increased gradually over a 6-h period of time. After a 7-h penetration period, the total AUC corresponded with 2.5% bioavailability relative to iv administration. In contrast with the G-agents C(+/-)P(+/-)-soman and (+/-)-sarin, stereospecificity in the sequestration of the two enantiomers of (+/-)-VX is not a prominent phenomenon. It appears that (+/-)-VX is substantially more persistent in vivo than the two G-agents. This persistence may undermine the efficacy of pretreatment with carbamates of percutaneous

  2. The effect of repeated nicotine administration on the performance of drug-naive rats in a five-choice serial reaction time task.

    Science.gov (United States)

    Blondel, A; Simon, H; Sanger, D J; Moser, P

    1999-11-01

    Nicotine improves cognitive performance both in animals and in humans, particularly in tests involving attentional processes. The five-choice serial reaction time task (5-CSRTT) is widely used as a model of attentional performance in rats, and previous studies have demonstrated effects of nicotine in this task on measures such as improved reaction time. Using a modified version of this task (in which rats were required to respond to the disappearance of one of five stimulus lights), we evaluated the effects of repeated nicotine administration (0.3 mg/kg, intraperitoneally, on three occasions over 7 days) in drug-naive rats. After the first administration, nicotine increased accuracy and reduced inappropriate responding (anticipatory responses and responses during time-out) compared to performance following vehicle administration on the preceding day. However, with repeated administration the improvement in accuracy disappeared, and other effects became apparent. Thus, after the third administration the main effects of nicotine were to increase inappropriate responding and to reduce reaction times. A fourth administration 1-2 weeks later produced similar results to the third administration, suggesting that the effects of nicotine were now constant. Despite the general increase in inappropriate responding, there was no impairment in accuracy. In contrast to the response to repeated nicotine, the performance of the rats on the 3 vehicle days remained constant. These data demonstrate that the administration of nicotine to drug-naive subjects improves performance in the 5-CSRTT but that with repeated administration this effect disappears and is replaced by a profile in which inappropriate and impulsive responding predominate.

  3. Paradoxical reaction of raynaud phenomenon following the repeated administration of iloprost in a patient with diffuse cutaneous systemic sclerosis.

    Science.gov (United States)

    Barreira, Rebeca Iglesias; García, Belén Bardán; López, Mónica Granero; Legazpi, Iria Rodríguez; Díaz, Hortensia Álvarez; Penín, Isaura Rodríguez

    2012-10-01

    To report a paradoxical reaction of Raynaud phenomenon following the repeated administration of iloprost in a patient with diffuse cutaneous systemic sclerosis with vascular involvement. In January 2006, a 40-year-old male was diagnosed with diffuse cutaneous systemic sclerosis with pulmonary, esophageal, cutaneous, and vascular involvement (Raynaud phenomenon, with digital ulcers on his hands). In December 2008, treatment with iloprost was started due to worsening disease. Nine cycles of iloprost were administered at a rate of 0.5-1 ng/kg/min (6 hours per day, for 5 days every 6-8 weeks); the patient tolerated this treatment well. However, on the fourth day of cycles 10 and 11, the patient developed paradoxical Raynaud phenomenon in the hand with perfusion when the infusion was increased to 1 ng/kg/min, requiring treatment to be stopped. Treatment was continued during cycles 12 and 13 at 0.5 ng/kg/min; the patient tolerated the treatment well, although paradoxical Raynaud phenomenon occurred when the rate of infusion was increased. Raynaud phenomenon is extremely common in patients with scleroderma, and often is severe. Iloprost has vasodilating, antiplatelet, cytoprotective, and immunomodulating properties, and has been found to be an efficacious alternative to nifedipine for the treatment of Raynaud phenomenon in patients with scleroderma. The Naranjo probability scale indicated that iloprost was the probable cause of the paradoxical Raynaud phenomenon in this patient. This case demonstrates a probable relationship between the rate of infusion of iloprost and the paradoxical reaction of Raynaud phenomenon.

  4. Effect of repeated oral administration of levofloxacin, enrofloxacin, and meloxicam on antioxidant parameters and lipid peroxidation in rabbits.

    Science.gov (United States)

    Khan, Adil Mehraj; Rampal, Satyavan; Sood, Naresh Kumar

    2016-03-09

    The effect of 21 days of repeated oral administration of levofloxacin and enrofloxacin both alone and in combination with meloxicam, on the oxidative balance in blood was evaluated in rabbits. Rabbits were randomly allocated to six groups of four animals each. Control group was gavaged 5% dextrose and 2% benzyl alcohol. Three groups were exclusively gavaged meloxicam (0.2 mg/kg body weight o.d.), levofloxacin hemihydrate (10 mg/kg body weight b.i.d 12 h), and enrofloxacin (20 mg/kg body weight o.d.), respectively. Two other groups were co-gavaged meloxicam with levofloxacin hemihydrate and enrofloxacin, respectively. A reduction (p meloxicam both alone and in combination with levofloxacin, whereas an increase (p meloxicam-alone treated group and inhibited (p meloxicam co-treated group. The activity of catalase was non-significantly different between various groups. Enrofloxacin-treated groups had higher (p meloxicam both alone and in combination with levofloxacin (p meloxicam.

  5. Upregulation of nucleoside triphosphate diphosphohydrolase-1 and ecto-5'-nucleotidase in rat hippocampus after repeated low-dose dexamethasone administration.

    Science.gov (United States)

    Drakulić, Dunja; Stanojlović, Miloš; Nedeljković, Nadežda; Grković, Ivana; Veličković, Nataša; Guševac, Ivana; Mitrović, Nataša; Buzadžić, Ivana; Horvat, Anica

    2015-04-01

    Although dexamethasone (DEX), a synthetic glucocorticoid receptor (GR) analog with profound effects on energy metabolism, immune system, and hypothalamic-pituitary-adrenal axis, is widely used therapeutically, its impact on the brain is poorly understood. The aim of the present study was to explore the effect of repeated low-dose DEX administration on the activity and expression of the ectonucleotidase enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. Ectonucleotidases tested were ectonucleoside triphosphate diphosphohydrolase 1-3 (NTPDase1-3) and ecto-5'-nucleotidase (eN), whereas the effects were evaluated in two brain areas that show different sensitivity to glucocorticoid action, hippocampus, and cerebral cortex. In the hippocampus, but not in cerebral cortex, modest level of neurodegenerative changes as well as increase in ATP, ADP, and AMP hydrolysis and upregulation of NTPDase1 and eN mRNA expression ensued under the influence of DEX. The observed pattern of ectonucleotidase activation, which creates tissue volume with enhanced capacity for adenosine formation, is the hallmark of the response after different insults to the brain.

  6. Characterization of metabolites in rats after intravenous administration of salvianolic acid for injection by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.

    Science.gov (United States)

    Miao, Jingzhuo; Sun, Wanyang; Huang, Jingyi; Liu, Xiaolin; Li, Shuming; Han, Xiaoping; Tong, Ling; Sun, Guoxiang

    2016-09-01

    It is an essential requirement to clarify the metabolites of traditional Chinese medicine (TCM) injections, which contain numerous ingredients, to assess their safe and effective use in clinic. Salvianolic acid for injection (SAFI), made from hydrophilic phenolic acids in Salvia miltiorrhiza Bunge, has been widely used for the treatment of cerebrovascular diseases, but information on its metabolites in vivo is still lacking. In the present study, we aimed to holistically characterize the metabolites of the main active ingredients in rat plasma, bile, urine and feces following intravenous administration of SAFI. An ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method was developed. Combining information on retention behaviors, multistage mass spectra and literature data, a total of eight prototypes and 52 metabolites were tentatively characterized. Metabolites originated from rosmarinic acid and salvianolic acid B comprised the majority of identified compounds. Meanwhile, four metabolites derived from salvianolic acid D and five from salvianolic acid B are reported for the first time. This study revealed that methylation, sulfation and glucuronidation were the major metabolic pathways of phenolic acids in SAFI in vivo. Furthermore, the developed UPLC/Q-TOF-MS method could also benefit the metabolic investigation of extracts and preparations in TCM with hydrophilic ingredients. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Development and Validation of an UPLC-Q-TOF-MS Method for Quantification of Fuziline in Beagle Dog After Intragastric and Intravenous Administration.

    Science.gov (United States)

    Gong, Xiao-hong; Li, Yan; Li, Yun-xia; Yuan, An; Zhao, Meng-jie; Zhang, Ruo-qi; Zeng, Dai-wen; Peng, Cheng

    2016-03-01

    A specific and sensitive UPLC-Q-TOF-MS method operated in the positive ion mode was developed and validated for the quantification of Fuziline in Beagle dog plasma. Fuziline and Neoline internal standard were separated on an Acquity UPLC BEH C18 column with the total running time of 4 min using gradient elution at the flow rate of 0.25 mL/min. The calibration curves for Fuziline showed good linearity in the concentrations ranging from 2 to 400 ng/mL with correlation coefficients (r) greater than 0.9971. The lower limit of quantification was 0.8 ng/mL. Intra- and interbatch relative standard deviations ranged from 2.11 to 3.11% and 3.12 to 3.81%, respectively. Fuziline was stable under different sample storage and processing conditions. The developed method was successfully applied to the comparative pharmacokinetic study of Fuziline in Beagle dog after intravenous and oral administration. Low absolute bioavailability of Fuziline (1.45 ± 0.76%) suggested a significant metabolism transformation extent in Beagle dog.

  8. Determination of alprostadil in rat plasma by ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry after intravenous administration.

    Science.gov (United States)

    Lin, Xia; Zhang, Yu; Cui, Yue; Wang, Lin; Wang, Jing; Tang, Xing

    2009-05-01

    A rapid, highly selective ultra performance liquid chromatography-electrospray ionisation-tandem mass spectrometry method (UPLC-ESI-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of alprostadil in rat plasma. After a simple sample preparation procedure involving a one-step liquid-liquid extraction, alprostadil and the internal standard, diphenhydramine, were chromatographed on an ACQUITY UPLC BEH C(18) column with gradient elution using a mobile phase consisting of acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.25 mL min(-1). The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode via an electrospray ionization (ESI) source. The calibration curve was linear (r(2)=0.99) over the concentration range 0.4-250.0 ng mL(-1), with a lower limit of quantification of 0.4 ng mL(-1) for alprostadil. The inter- and intra-day precision (%R.S.D.) was less than 8.5% and 2.4%, respectively, and the accuracy (RE%) was between 9.3% and 1.0% (n=6). Alprostadil in rat plasma was stable when stored at room temperature for 0.5h and at -20 degrees C for two weeks. The method was very rapid, simple and reliable, and was employed for the first time for the pharmacokinetic studies of alprostadil in rats after a single intravenous administration of 50 microg kg(-1).

  9. Plasma pharmacokinetics, bioavailability and tissue distribution of agnuside following peroral and intravenous administration in mice using liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Ramakrishna, Rachumallu; Bhateria, Manisha; Singh, Rajbir; Puttrevu, Santosh Kumar; Bhatta, Rabi Sankar

    2016-06-01

    Agnuside (AGN), an iridoid glycoside, is the chemotaxonomic marker of the genus Vitex which has gained enormous attention by virtue of its potential health benefits. Regardless of claiming many therapeutic applications reports demonstrating its pharmacokinetics or quantification in biomatrices are lacking. This is the first report which presents a sensitive liquid chromatography coupled to a tandem mass spectrometry (LC-MS/MS) method for the quantification of AGN in mice plasma and various tissues (including liver, intestine, spleen, kidney, heart, lungs and brain). AGN was extracted from the biological samples using protein precipitation followed by liquid-liquid extraction and the separation was achieved on C18 reversed phase column with a mobile phase consisted of 0.1% formic acid in acetonitrile-0.1% formic acid in triple distilled water (92:8, v/v) at a flow rate of 0.7mL/min. The MS/MS detection was performed by electrospray ionization (ESI) using multiple reaction monitoring (MRM) in negative scan mode. The bioanalytical method was found linear over the concentration range of 1-4000ng/mL for plasma and tissue homogenates (r(2)≥0.990). The lower limit of quantitation (LLOQ) for all matrices was 1ng/mL. Intra-day and inter-day variance and accuracy ranged from 90 to 110% and 1-10%, respectively. Matrix effect and recoveries were well within the satisfactory limits. The validated method was applied successfully to measure AGN concentrations in plasma and tissues following intravenous (i.v.) and peroral (p.o.) administration to mice. Maximal AGN concentrations in plasma and tissues were reached within 30-45min. The mean absolute bioavailability (%F) of AGN was∼0.7%. After oral administration, AGN was most abundant in intestine, followed by kidney, liver, spleen, brain, lungs and heart. The identified target tissues of AGN may help in understanding its pharmacological action in vivo.

  10. [Effect of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic, on the bone marrow function of rabbits. (2) Repeated intravenous injections].

    Science.gov (United States)

    Tone, H; Kiyosaki, T; Shirai, M

    1986-02-01

    (2''R)-4'-O-Tetrahydropyranyladriamycin-HCl (THP), a new antitumor antibiotic, was intravenously injected to New Zealand White rabbits at a dose of 2.5 mg/kg every 2 weeks for 6 weeks (3 courses) or at a dose of 0.5 mg/kg/day daily for the first 5 days of a 2-week course for 6 weeks (3 courses). The total dose was 7.5 mg/kg in both dosing schedules. The peripheral leucocyte and erythrocyte counts decreased. The leucocyte count decreased to 57% of the initial count on Day 3 in the first course and then increased gradually. The decrease was smaller in the divided dosing schedule than the single dosing. The nucleated cells, especially immatured myelocytes and erythroids reduced remarkably. Subsequently the matured myelocyte ratio in bone marrow cell constituents increased and the M/E ratio increased. These changes were observed on Day 3 and reverted by Day 9 in each course. The divided dosing schedule resulted in a higher nadir. All the changes in the peripheral blood and the bone marrow reverted even after the 3 course-treatment.

  11. Safety of poly (ethylene glycol-coated perfluorodecalin-filled poly (lactide-co-glycolide microcapsules following intravenous administration of high amounts in rats

    Directory of Open Access Journals (Sweden)

    Katja B. Ferenz

    2014-01-01

    Intravenous infusion of high amounts of PFD-filled PLGA microcapsules was tolerated temporarily but associated with severe side effects such as hypotension and organ damage. Short-chained PVA displays excellent biocompatibility and thus, can be utilized as emulsifier for the preparation of drug carriers designed for intravenous use.

  12. Repeated administration of D-amphetamine induces loss of [I-123]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study

    NARCIS (Netherlands)

    J. Booij; K. de Bruin; W.B. Gunning

    2006-01-01

    In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in arnphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of

  13. A study of pharmacokinetic interactions among co-existing ingredients in Viscum coloratum after intravenous administration of three different preparations to rats

    Directory of Open Access Journals (Sweden)

    Yuying Ma

    2015-01-01

    Full Text Available Background: Viscum coloratum (Komar Nakai, known as Hujisheng in china, has been widely used as a herb medicine to treat a variety of diseases, including cardiovascular diseases, cancer, hypertension, hepatitis and hemorrhage. Objective: The aim was to investigate pharmacokinetic interactions among co existing ingredients in V. coloratum after intravenous administration of three different preparations (four monomer solutions, the mixture of them and Viscum coloratum extracts to rats. Materials and Methods: After protein precipitation pretreatment with plasma samples, high performance liquid chromatographic methods were developed and applied to quantitatively determinate the four components [syringin (Syri, homoeriodictyol 7 O-β-D glycoside (Hedt III, homoeriodictyol 7 O-β-D apiose (1 → 2-β-D glycoside (Hedt II and homoeriodictyol 7 O-β-D apiosiyl (1 → 5-β-D apiosyl (1 → 2-β-D glycoside (Hedt I].The pharmacokinetic parameters (Area under the curve [AUC (0-t], AUC (0-∞, t1/2 were calculated using DAS 2.1 software (Chinese Pharmacological Society,Shanghai,China and compared statistically by One way analysis of variance using SPSS software (18.0, Chicago, IL, USA with P < 0.05 considered statistically significant. Results: Good linearities were achieved in the measured concentration range with R2 it0.9920. Precision, accuracy and extraction recovery were all within the acceptable range. For Syri, there was a significant difference only on t1/2 among three treatment groups. For Hedt I, Hedt II and Hedt III, three flavonoid glycosides, the change of AUC (0-t, AUC (0-∞ and t1/2 were markedly distinctive and even converse. Conclusion: Complex, extensive pharmacokinetic interactions were observed among these components in V. coloratum. They were mutually influenced by the in vivo absorption, distribution, metabolism and elimination. The result suggested traditional Chinese medicine was a complicated system, and we should take a scientific

  14. Intravenous administration of adipose tissue-derived stem cells enhances nerve healing and promotes BDNF expression via the TrkB signaling in a rat stroke model

    Directory of Open Access Journals (Sweden)

    Li X

    2016-06-01

    Full Text Available Xin Li,1 Wei Zheng,2 Hongying Bai,1 Jin Wang,3 Ruili Wei,1 Hongtao Wen,3 Hanbing Ning3 1Department of Neurology, 2Department of Nursing, The Second Affiliated Hospital of Zhengzhou University, 3Department of Digestive Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China Abstract: Previous studies have shown the beneficial effects of adipose-derived stem cells (ADSCs transplantation in stroke. However, the molecular mechanism by which transplanted ADSCs promote nerve healing is not yet elucidated. In order to make clear the molecular mechanism for the neuroprotective effects of ADSCs and investigate roles of the BDNF–TrkB signaling in neuroprotection of ADSCs, we, therefore, examined the neurological function, brain water content, and the protein expression in middle cerebral artery occlusion (MCAO rats with or without ADSCs transplantation. ADSCs were transplanted intravenously into rats at 30 minutes after MCAO. K252a, an inhibitor of TrkB, was administered into rats by intraventricular and brain stereotaxic injection. Modified neurological severity score tests were performed to measure behavioral outcomes. The results showed that ADSCs significantly alleviated neurological deficits and reduced brain water content in MCAO rats. The protein expression levels of BDNF and TrkB significantly increased in the cortex of MCAO rats with ADSCs treatment. However, K252a administration reversed the ADSCs-induced elevation of BDNF, TrkB, and Bcl-2 and reduction of Bax protein in MCAO rats. ADSCs promote BDNF expression via the TrkB signaling and improve functional neurological recovery in stroke rats. Keywords: stroke, adipose tissue-derived stem cells, brain-derived neurotrophic factor, TrkB

  15. Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings

    Directory of Open Access Journals (Sweden)

    Jie Li

    2017-06-01

    Full Text Available Although arctigenin (AG has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro. In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK profiles of AG with different drug-delivery manners, including intravenous (i.v, hypodermic injection (i.h, and sublingual (s.l administration. The data shows that AG exhibited a strong absorption capacity in both rats and beagle dogs (absorption rate < 1 h, a high absorption degree (absolute bioavailability > 100%, and a strong elimination ability (t1/2 < 2 h. The tissue distributions of AG at different time points after i.h showed that the distribution of AG in rat tissues is rapid (2.5 h to reach the peak and wide (detectable in almost all tissues and organs. The AG concentration in the intestine was the highest, followed by that in the heart, liver, pancreas, and kidney. In vitro, AG were incubated with human, monkey, beagle dog and rat liver microsomes. The concentrations of AG were detected by UPLC-MS/MS at different time points (from 0 min to 90 min. The percentages of AG remaining in four species’ liver microsomes were human (62 ± 6.36% > beagle dog (25.9 ± 3.24% > rat (15.7 ± 9% > monkey (3.69 ± 0.12%. This systematic investigation of pharmacokinetic profiles of arctigenin (AG in vivo and in vitro is worthy of further exploration.

  16. Pharmacokinetics of DA-125, a new anthracycline, after intravenous administration to uranyl nitrate-induced acute renal failure rats or protein-calorie malnutrition rats.

    Science.gov (United States)

    Kim, Y G; Yoon, E J; Yoon, W H; Shim, H J; Lee, S D; Kim, W B; Yang, J; Lee, M G

    1996-04-01

    The pharmacokinetics of DA-125 were compared after intravenous (i.v.) administration of the drug, 10 mg kg-1, to control male Sprague-Dawley rats (n = 9) and uranyl nitrate-induced acute renal failure (U-ARF, n = 12) rats, or male Sprague-Dawley rats fed on a 23% (control, n = 8) or a 5% (protein-calorie malnutrition, PCM, n = 9) protein diet. After i.v. administration of DA-125, almost 'constant' plasma concentrations of M1, M2, and M4 were maintained from 1-2 h to 8-10 h in all rat groups due to the continuous formation of M2 from M1 and M4 from M3. The plasma concentrations of M3 were the lowest among M1-M4 for all rat groups due to the rapid and almost complete conversion of M3 to M4 and other metabolite(s). The AUCt values of M1 (115 against 82.5 micrograms min mL-1), M2 (33.0 against 23.6 micrograms min mL-1), and M4 (26.3 against 15.1 micrograms min mL-1) were significantly higher in the U-ARF rats than in the control rats. The percentages of i.v. dose excreted in 24 h urine as M1 (under the detection limit against 0.316%), M2 (under the detection limit against 5.58%), and M4 (0.0174 against 0.719%)--expressed in terms of DA-125--were significantly lower in the U-ARF rats than in the control rats, and this could be due to the decreased kidney function in the U-ARF rats. However, the percentages of i.v. dose recovered from the GI tract at 24 h as M1 (0.0532% against under the detection limit), M3 (0.0286% against under the detection limit), and M4 (0.702% against 0.305%)--expressed in terms of DA-125--were significantly greater in the U-ARF rats than in the control rats. All U-ARF rats had ascites, but the concentrations of M1 (0.0320 micrograms mL-1), M2 (0.0265 micrograms mL-1), M3 (under the detection limit), and M4 (0.032 micrograms mL-1) in the ascites from one rat were almost negligible. The plasma concentrations and most of the pharmacokinetic parameters of M1, M2, and M4 were not significantly different between the PCM rats and their control rats.

  17. Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab

    Directory of Open Access Journals (Sweden)

    Theodore-Oklota C

    2016-09-01

    Full Text Available Christina Theodore-Oklota,1 Louise Humphrey,2 Christof Wiesner,1 Gabriel Schnetzler,3 Stacie Hudgens,4 Alicyn Campbell1 1Genentech, South San Francisco, CA, USA; 2Adelphi Values, Macclesfield, Cheshire, UK; 3F. Hoffmann La-Roche Ltd, Basel, Switzerland; 4Clinical Outcomes Solutions, Tucson, AZ, USA Background: A subcutaneous (SC formulation of rituximab (MabThera®/Rituxan® has been developed that could reduce administration time and improve patient satisfaction with treatment. The Rituximab Administration Satisfaction Questionnaire (RASQ was created to assess patients’ perceptions and satisfaction with rituximab SC (RASQ-SC or rituximab intravenous (RASQ-IV. We assessed the content validity and psychometric properties of RASQ in patients with non-Hodgkin lymphoma.Methods: Face and content validity of RASQ-SC and RASQ-IV were qualitatively assessed using 60-minute combined concept elicitation and cognitive debriefing interviews. Psychometric validation of RASQ (item performance and reliability was assessed quantitatively against the established Cancer Therapy Satisfaction Questionnaire (CTSQ, using questionnaire data from the PrefMab (NCT01724021 and MabCute (NCT01461928 clinical studies.Results: RASQ-IV demonstrated excellent coverage of concepts relevant to patients’ (n=10 own treatment experiences and no new concepts were identified. Patients’ expectations of rituximab SC were conceptually consistent with items included in the RASQ-SC, suggesting that the tool is also conceptually adequate. In 1,051 patients from PrefMab and MabCute, correlations with domains such as “RASQ: Physical Impacts” and “CTSQ: Feelings About Side Effects”, “RASQ: Physical Impacts” and “CTSQ: Satisfaction With Therapy”, and “RASQ: Satisfaction” and “CTSQ: Satisfaction With Therapy”, achieved moderate-to-high correlations (>0.4 for convergent domains and <0.3 for divergent domains.Conclusion: This study supports the qualitative face and

  18. Risk of sensitization in healthy adults following repeated administration of rdESAT-6 skin test reagent by the Mantoux injection technique

    DEFF Research Database (Denmark)

    Lillebaek, Troels; Bergstedt, Winnie; Tingskov, Pernille N;

    2009-01-01

    1 open clinical trial was to assess the sensitization risk and safety of repeated administration of rdESAT-6 reagent in 31 healthy adult volunteers. Three groups of volunteers received two fixed doses of 0.1 microg rdESAT-6 28, 56 or 112 days apart, respectively. After the second injection......Limited specificity of the tuberculin skin test incited the development of the intradermal Mycobacterium tuberculosis-specific rdESAT-6 skin test. Animal studies have shown, however, that there is a possible risk of sensitization when repeated injections of rdESAT-6 are given. The aim of this phase...

  19. Efficacy and safety of out-of-hospital intravenous metoprolol administration in anterior ST-segment elevation acute myocardial infarction: insights from the METOCARD-CNIC trial

    OpenAIRE

    Mateos, Alonso; García Lunar, Inés; García Ruiz, José María; Pizarro, Gonzalo; Fernández Jiménez, Rodrigo; Huertas, Pilar; García Álvarez, Ana; Fernández-Friera, Leticia; Bravo, Jesús; Flores Arias, José; Barreiro, María V.; Chayán Zas, Luisa; Corral, Ervigio; Fuster, Valentín; Sánchez Brunete, Vicente

    2015-01-01

    We seek to examine the efficacy and safety of prereperfusion emergency medical services (EMS)–administered intravenous metoprolol in anterior ST-segment elevation myocardial infarction patients undergoing eventual primary angioplasty. This is a prespecified subgroup analysis of the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction trial population, who all eventually received oral metoprolol within 12 to 24 hours. We studied patients receiving intravenous metoprol...

  20. [Intravenous administration of a tissue plasminogen activator beyond 3 hours of the onset of acute ischemic stroke--MRI-based decision making].

    Science.gov (United States)

    Kakuda, Wataru; Abo, Masahiro

    2008-10-01

    After large CT-based clinical trials have failed to prove the benefits of intravenous tissue plasminogen activator (tPA) administration for ischemic stroke patients beyond 3 hours of the onset of the concept of PWI/DWI mismatch which is the volume difference between a PWI lesion and DWI lesion on MRI scans, has been proposed to facilitate the selection of patients with a salvageable area. PWI/DWI mismatch is considered to represent the tissue that is not irreversibly injured and can respond to early reperfusion therapy. When an ischemic lesion is divided into 4 regions, namely, ischemic core, reversible DWI lesion, penumbra and benign oligemia, both the reversible DWI lesion and penumbra are considered to be an optimal targets for thrombolysis. In order to clarify the clinical significance of PWI/DWI mismatch in the selection of candidates for tPA therapy, some multicenter trials were performed. The results of DIAS (desmoteplase in acute ischemic stroke)/DEDAS (dose escalation of desmoteplase for acute ischemic stroke)/DIAS-2 did not difinitly demonstrate the clinical benefits of desmoteplase administration in patients with PWI/DWI mismatch between 3 to 9 hours of onset; in fact, DIAS-2 could not prove any effect of the drug. DEFUSE (diffusion and perfusion imaging evaluation for understanding stroke evolution), in which tPA was administered to all participants between 3 to 6 hours of stroke onset, showed that the occurrence of early reperfusion led to a favorable clinical response in patients with PWI/DWI mismatch. In contrast, early reperfusion was not beneficial in patients without PWI/DWI mismatch. In EPITHET (echoplanar imaging thrombolysis evaluation trial), stroke patients who showed PWI/DWI mismatch after 3 to 6 hours of the onset were assigned to receive either alteplase or placebo administration: lesion growth was lesser in patients with alteplase than in those who received placebo, although the difference was not statistically significant because of a

  1. Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Shin-Ae; Tsolmon, Bilegtsaikhan [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States); Mann, Aman P. [Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030 (United States); Zheng, Wei; Zhao, Lichao; Zhao, Yan Daniel [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States); Volk, David E.; Lokesh, Ganesh L.-R. [Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030 (United States); Morris, Lynsie; Gupta, Vineet; Razaq, Wajeeha [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States); Rui, Hallgeir [Thomas Jefferson University, 1020 Locust St, Philadelphia, PA 19107 (United States); Suh, K. Stephen [John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601 (United States); Gorenstein, David G. [Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030 (United States); Tanaka, Takemi, E-mail: takemi-tanaka@ouhsc.edu [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States)

    2015-08-15

    The medical applications of aptamers have recently emerged. We developed an antagonistic thioaptamer (ESTA) against E-selectin. Previously, we showed that a single injection of ESTA at a dose of 100 μg inhibits breast cancer metastasis in mice through the functional blockade of E-selectin. In the present study, we evaluated the safety of different doses of intravenously administered ESTA in single-dose acute and repeat-dose subacute studies in ICR mice. Our data indicated that intravenous administration of up to 500 μg ESTA did not result in hematologic abnormality in either study. Additionally, intravenous injection of ESTA did not affect the levels of plasma cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, GM-CSF, IFN-γ, and TNF-α) or complement split products (C3a and C5a) in either study. However, repeated injections of ESTA slightly increased plasma ALT and AST activities, in accordance with the appearance of small necrotic areas in the liver. In conclusion, our data demonstrated that intravenous administration of ESTA does not cause overt hematologic, organs, and immunologic responses under the experimental conditions. - Highlights: • Intravenous administration of ESTA was well tolerated. • ESTA up to 500 μg does not cause hematologic, organs, and immunologic responses. • ESTA-mediated hepatic abnormality was considered minor.

  2. Administration

    DEFF Research Database (Denmark)

    Bogen handler om den praksis, vi kalder administration. Vi er i den offentlige sektor i Danmark hos kontorfolkene med deres sagsmapper, computere, telefoner,, lovsamlinger,, retningslinier og regneark. I bogen udfoldes en mangfoldighed af konkrete historier om det administrative arbejde fra...... forskellige områder i den offentlige sektor. Hensigten er at forstå den praksis og faglighed der knytter sig til det administrative arbejde...

  3. Radip induction of ether anaesthesia and controlled maintenacne by a combination of intravenous and inhalation administration without the risk of explosion.

    Science.gov (United States)

    Zwart, A; De Leeuw, L; Van Dieren, A; Vree, T B; Saleh, S; Garcia-Martinez, R; Trimbos, H

    1976-06-01

    The induction and maintenance of anaesthesia with ether using a combined intravenous infusion and a constant low inspired concentration are discribed. Predictions from a mathematical model were checked against animal experiments. Anaesthesia occurred within 5 min. The mehtod obviates the need for explosive mixtures.

  4. Pharmacokinetics of repeated sodium salicylate administration to laying hens: evidence for time dependent increase in drug elimination from plasma and eggs.

    Directory of Open Access Journals (Sweden)

    Błażej Poźniak

    Full Text Available Salicylates were the first non-steroid anti-inflammatory drugs (NSAIDs to be used in any species and are still widely used in humans and livestock. However, the data on their pharmacokinetics in animals is limited, especially after repeated administration. Evidence exist that in chickens (Gallus gallus salicylate (SA may induce its own elimination. The aim of this study was to investigate salicylate pharmacokinetics and egg residues during repeated administration of sodium salicylate (SS to laying hens. Pharmacokinetics of SA was assessed during 14 d oral administration of SS at daily doses of 50 mg/kg and 200 mg/kg body weight to laying hens. On the 1st, 7th and 14th d a 24 h-long pharmacokinetic study was carried out, whereas eggs were collected daily. Salicylate concentrations in plasma and eggs were determined using high-performance liquid chromatography with ultraviolet detection and pharmacokinetic variables were calculated using a non-compartmental model. Mean residence time (MRT, minimal plasma concentration (Cmin, C16h and elimination half-life (T1/2el of SA showed gradual decrease in layers administered with a lower dose. Total body clearance (ClB increased. Layers administered with the higher dose showed a decrease only in the T1/2el. In the low dose group, SA was found only in the egg white and was low throughout the experiment. Egg whites from the higher dose group showed initially high SA levels which significantly decreased during the experiment. Yolk SA levels were lower and showed longer periods of accumulation and elimination. Repeated administration of SS induces SA elimination, although this effect may differ depending on the dose and production type of a chicken. Decreased plasma drug concentration may have clinical implications during prolonged SS treatment.

  5. Repeated administration of alpha7 nicotinic acetylcholine receptor (nAChR) agonists, but not positive allosteric modulators, increases alpha7 nAChR levels in the brain

    DEFF Research Database (Denmark)

    Christensen, Ditte Z; Mikkelsen, Jens D; Hansen, Henrik H;

    2010-01-01

    -induced phosphorylation of Erk2 in the prefrontal cortex occurs following acute, but not repeated administration. Our results demonstrate that repeated agonist administration increases the number of alpha7 nAChRs in the brain, and leads to coupling versus uncoupling of specific intracellular signaling....... Here we investigate the effects of repeated agonism on alpha7 nAChR receptor levels and responsiveness in vivo in rats. Using [(125)I]-alpha-bungarotoxin (BTX) autoradiography we show that acute or repeated administration with the selective alpha7 nAChR agonist A-582941 increases the number of alpha7 n......-120596 and NS1738 do not increase [(125)I]-BTX binding. Furthermore, A-582941-induced increase in Arc and c-fos mRNA expression in the prefrontal cortex is enhanced and unaltered, respectively, after repeated administration, demonstrating that the alpha7 nAChRs remain responsive. Contrarily, A-582941...

  6. Pharmacokinetic Study of Intravenous Acetaminophen Administered to Critically Ill Multiple-Trauma Patients at the Usual Dosage and a New Proposal for Administration.

    Science.gov (United States)

    Fuster-Lluch, Oscar; Zapater-Hernández, Pedro; Gerónimo-Pardo, Manuel

    2017-04-17

    The pharmacokinetic profile of intravenous acetaminophen administered to critically ill multiple-trauma patients was studied after 4 consecutive doses of 1 g every 6 hours. Eleven blood samples were taken (predose and 15, 30, 45, 60, 90, 120, 180, 240, 300, and 360 minutes postdose), and urine was collected (during 6-hour intervals between doses) to determine serum and urine acetaminophen concentrations. These were used to calculate the following pharmacokinetic parameters: maximum and minimum concentrations, terminal half-life, area under serum concentration-time curve from 0 to 6 hours, mean residence time, volume of distribution, and serum and renal clearance of acetaminophen. Daily doses of acetaminophen required to obtain steady-state minimum (bolus dosing) and average plasma concentrations (continuous infusion) of 10 μg/mL were calculated (10 μg/mL is the presumed lower limit of the analgesic range). Data are expressed as median [interquartile range]. Twenty-two patients were studied, mostly young (age 44 [34-64] years) males (68%), not obese (weight 78 [70-84] kg). Acetaminophen concentrations and pharmacokinetic parameters were these: maximum concentration 33.6 [25.7-38.7] μg/mL and minimum concentration 0.5 [0.2-2.3] μg/mL, all values below 10 μg/mL and 8 below the detection limit; half-life 1.2 [1.0-1.9] hours; area under the curve for 6 hours 34.7 [29.7-52.7] μg·h/mL; mean residence time 1.8 [1.3-2.6] hours; steady-state volume of distribution 50.8 [42.5-66.5] L; and serum and renal clearance 28.8 [18.9-33.7] L/h and 15 [11-19] mL/min, respectively. Theoretically, daily doses for a steady-state minimum concentration of 10 μg/mL would be 12.2 [7.8-16.4] g/day (166 [112-202] mg/[kg·day]); for an average steady-state concentration of 10 μg/mL, they would be 6.9 [4.5-8.1] g/day (91 [59-111] mg/[kg·day]). In conclusion, administration of acetaminophen at the recommended dosage of 1 g per 6 hours to critically ill multiple-trauma patients yields

  7. Repeated intrathecal administration of plasmid DNA complexed with polyethylene glycol-grafted polyethylenimine led to prolonged transgene expression in the spinal cord.

    Science.gov (United States)

    Shi, L; Tang, G P; Gao, S J; Ma, Y X; Liu, B H; Li, Y; Zeng, J M; Ng, Y K; Leong, K W; Wang, S

    2003-07-01

    Gene delivery into the spinal cord provides a potential approach to the treatment of spinal cord traumatic injury, amyotrophic lateral sclerosis, and spinal muscular atrophy. These disorders progress over long periods of time, necessitating a stable expression of functional genes at therapeutic levels for months or years. We investigated in this study the feasibility of achieving prolonged transgene expression in the rat spinal cord through repeated intrathecal administration of plasmid DNA complexed with 25 kDa polyethylenimine (PEI) into the lumbar subarachnoid space. With a single injection, DNA/PEI complexes could provide transgene expression in the spinal cord 40-fold higher than naked plasmid DNA. The transgene expression at the initial level persisted for about 5 days, with a low-level expression being detectable for at least 8 weeks. When repeated dosing was tested, a 70% attenuation of gene expression was observed following reinjection at a 2-week interval. This attenuation was associated with apoptotic cell death and detected even using complexes containing a noncoding DNA that did not mediate any gene expression. When each component of the complexes, PEI polymer or naked DNA alone, were tested in the first dosing, no reduction was found. Using polyethylene glycol (PEG)-grafted PEI for DNA complexes, no attenuation of gene expression was detected after repeated intrathecal injections, even in those rats receiving three doses, administered 2 weeks apart. Lumbar puncture is a routine and relatively nontraumatic clinical procedure. Repeated administration of DNA complexed with PEG-grafted PEI through this less invasive route may prolong the time span of transgene expression when needed, providing a viable strategy for the gene therapy of spinal cord disorders.

  8. Acute and repeated intranasal oxytocin administration exerts anti-aggressive and pro-affiliative effects in male rats

    NARCIS (Netherlands)

    Calcagnoli, Federica; Kreutzmann, Judith C.; de Boer, Sietse F.; Althaus, Monika; Koolhaas, Jaap M.

    2015-01-01

    Socio-emotional deficits and impulsive/aggressive outbursts are prevalent symptoms of many neuropsychiatric disorders, and intranasal administration of oxytocin (OXT) is emerging as a putative novel therapeutic approach to curb these problems. Recently, we demonstrated potent anti-aggressive and pro

  9. Pharmacokinetics of marbofloxacin in pigs after intravenous and intramuscular administration of a single dose of 8 mg/kg: dose proportionality, influence of the age of the animals and urinary elimination.

    Science.gov (United States)

    Schneider, M; Paulin, A; Dron, F; Woehrlé, F

    2014-12-01

    The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of dose and animal age following intravenous and intramuscular administration of a 16% solution (Forcyl(®) ). The absolute bioavailability of marbofloxacin as well as the dose proportionality was evaluated in 27-week-old fattening pigs. Blood PK and urinary excretion of marbofloxacin were evaluated after a single intramuscular dose of 8 mg/kg in 16-week-old male pigs. An additional group of 12-week-old weaned piglets was used for the evaluation of age-related kinetics. The plasma and urine concentration of marbofloxacin was determined using a HPLC method. Pharmacokinetic parameters were calculated using noncompartmental methods. After intravenous administration in 27-week-old fattening pigs, the total body clearance was 0.065 L/h·kg. After intramuscular administration to the same animals, the mean observed Cmax was 6.30 μg/mL, and the AUCINF was 115 μg·h/mL. The absolute bioavailability was 91.5%, and dose proportionality was shown within the dose range of 4-16 mg/kg. The renal clearance was about half of the value of the total clearance. The total systemic clearance values significantly decreased as a function of age, being 0.092 L/h·kg and 0.079 L/h·kg in pigs aged 12 and 16 weeks, respectively.

  10. Repeated 2% sevoflurane administration in 7‑ and 60-day-old rats : Neurotoxicity and neurocognitive dysfunction.

    Science.gov (United States)

    Huang, He; Liu, Cun-Ming; Sun, Jie; Jin, Wen-Jie; Wu, Yu-Qing; Chen, Jing

    2017-09-15

    Sevoflurane is one of the most widely used inhalation anesthetics in pediatric anesthesia. A large number of studies have demonstrated that repeated treatment with high concentrations or long durations of sevoflurane anesthesia during the neonatal period can induce neuroapoptosis and long-term learning disability. In clinical practice, we observed that a subset of patients underwent minor surgery under sevoflurane anesthesia more than once from birth to adolescence. Therefore, this research was conducted to investigate whether a 2% concentration of sevoflurane (clinically relevant usage of sevoflurane) for 1 h (a short duration) can induce neuroapoptosis and neurocognitive dysfunction in adolescent rats that received sevoflurane (2% for 1 h) during the neonatal period. Group I: neonatal rats at postnatal day 7 (PND-7) were treated with oxygen under controlled conditions and then raised to PND-60. Group II: PND-7 rats were treated with 2% sevoflurane for 1 h and then raised to PND-60. Group III: the PND-60 rats were treated with 2% sevoflurane for 1 h and in group IV the PND-7 rats were treated with 2% sevoflurane for 1 h and then anesthetized with 2% sevoflurane for 1 h at PND-60 again. The expression of caspase-3, Bax and Bcl-2 in the hippocampal dentate gyrus (DG) were measured by Western blot analysis. Neuroapoptosis in the hippocampal DG was assessed using NeuN/caspase-3 double-immunofluorescence staining. Spatial reference memory was tested by the Morris water maze test. The present data showed that sevoflurane (2% for 1 h) did not induce obvious hippocampal neuroapoptosis in the PND-7 rats and PND-60 rats; their performance in hippocampal-dependent spatial memory was not significantly impaired; however, the rats in group IV showed poor performance in the Morris water maze test and the neuroapoptosis in group IV was significantly increased. Our findings suggested that sevoflurane can induce neuroapoptosis and cognitive dysfunction in

  11. Toxicokinetics of α-thujone following intravenous and gavage administration of α-thujone or α- and β-thujone mixture in male and female F344/N rats and B6C3F1 mice

    Energy Technology Data Exchange (ETDEWEB)

    Waidyanatha, Suramya, E-mail: waidyanathas@niehs.nih.gov [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Johnson, Jerry D.; Hong, S. Peter [Battelle Memorial Institute, Columbus, OH 43201 (United States); Robinson, Veronica Godfrey [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Gibbs, Seth; Graves, Steven W. [Battelle Memorial Institute, Columbus, OH 43201 (United States); Hooth, Michelle J.; Smith, Cynthia S. [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States)

    2013-09-01

    Plants containing thujone have widespread use and hence have significant human exposure. α-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of α-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of α-thujone or a mixture of α- and β-thujone (which will be referred to as α,β-thujone). Absorption of α-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of α-thujone following administration of α-thujone or α,β-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males following administration of either test article although a sex difference was not observed in mice. C{sub max} and AUC{sub ∞} increased greater than proportional to the dose in female rats following administration of α-thujone and in male and female mice following administration of α,β-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC{sub ∞} for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of α-thujone and α,β-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, α-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of α-thujone and α,β-thujone where females were more sensitive than males of both species to α-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to α-thujone concentration. - Highlights: • Absorption of α-thujone following gavage administration was rapid in rats and mice. • Rats undergo higher exposure to α-thujone than mice. • α-Thujone brain

  12. Effect of repeated oral administration of Bifidobacterium longum BB536 on apomorphine-induced rearing behavior in mice

    OpenAIRE

    ORIKASA, Shuzo; NABESHIMA, Kazumi; Iwabuchi, Noriyuki; Xiao, Jin-zhong

    2016-01-01

    Schizophrenia is a chronic psychiatric illness. Disruption of the dopaminergic system has been suggested to be the pathogenic cause of this disease. The effect of Bifidobacterium longum BB536 (BB536) on schizophrenic behavior was investigated in an animal model. Daily administration of BB536 (109 CFU/mouse, p.o. for 2 weeks) was found to reduce rearing behavior augmented by the dopamine receptor agonist apomorphine and to decrease the resting level of plasma corticosterone and the ratio of ky...

  13. Aminothiol Receptors for Decorporation of Intravenously Administered 60Co in the Rat

    Energy Technology Data Exchange (ETDEWEB)

    Levitskaia, Tatiana G.; Morris, James E.; Creim, Jeffrey A.; Woodstock, Angela D.; Luders, Teresa; Curry, Terry L.; Thrall, Karla D.

    2010-01-01

    The reported investigation provides a comparison of the oral decorporation efficacy of L-glutathione (GSH), L-cysteine (Cys), and a liposomal GSH formulation (ReadiSorb) toward systemic cobalt-60 (60Co) to that observed following intravenous administration of GSH and Cys in F344 rats. L-histidine (His) was tested intravenously to compare in vivo efficacy of the aminothiol GSH and Cys chelators with that of aminoimidazole (His) chelator. 60Co was administered to animals by intravenous injection, followed by intravenous or oral gavage doses of a chelator repeated at 24 hour intervals for a total of 5 doses. The results suggest that GSH and Cys are potent decorporation agents for 60Co in the rat model, although the efficacy of treatment depends largely on systemic availability of a chelator. The intravenous GSH or Cys were most effective in reducing tissue 60Co levels and in increasing excretion of radioactivity compared to control animals. Liposomal encapsulation was found to markedly enhance the oral bioavailability of GSH compared to non-formulated GSH. Oral administration of ReadiSorb reduced 60Co levels in nearly all tissues by 12-43% compared to that observed for non-formulated GSH. Efficacy of oral Cys was only slightly reduced in comparison with intravenous Cys. Further studies to optimize the dosing regimen in order to maximize decorporation efficiency are warranted.

  14. Nanosuspension formulations of poorly water-soluble compounds for intravenous administration in exploratory toxicity studies: in vitro and in vivo evaluation.

    Science.gov (United States)

    Fujimura, Hisako; Komasaka, Takao; Tomari, Taizo; Kitano, Yasunori; Takekawa, Kouji

    2016-10-01

    This study was conducted to investigate the use of a nanosuspension for intravenous injection into dogs to increase exposure without toxic additives for preclinical studies in the discovery stage. Nanosuspensions were prepared with a mixer mill and zirconia beads with a vehicle of 2% (w/v) poloxamer 338, which was confirmed to lead to no histamine release in dogs. Sterilized nanosuspensions of poorly water-soluble compounds, cilostazol (Cil), spironolactone (Spi) and probucol (Pro), at 10 mg ml(-1) were obtained by milling for 30 min, followed by autoclaving for 20 min at 121 °C and milling for 30 min (mill-autoclave-mill method). The particle sizes (d50) of Cil, Spi and Pro were 0.554, 0.484 and 0.377 µm, respectively, and the percentages of the nominal concentration were 79.1%, 99.6% and 75.4%, respectively. In chromatographic data, no extra peaks were observed. The particle size of Cil was 0.564 µm after storage for 16 days at 2-8 °C. Cil in nanosuspension, but not in microsuspension, rapidly dissolved in dog plasma. Cil nanosuspension at 0.4 mg kg(-1) and Cil saline solution at 0.03 mg kg(-1) , around the saturation solubility, were intravenously administered to dogs. Nanosuspension increased exposure. The versatility of the mill-autoclave-mill method was checked for 15 compounds, and the particle size of 12 compounds was in the nano range. The nanosuspension optimized in this study may be useful for intravenous toxicological and pharmacological studies in the early stage of drug development. Copyright © 2016 John Wiley & Sons, Ltd.

  15. The effects of repeated administration of camphor-crataegus berry extract combination on blood pressure and on attentional performance - a randomized, placebo-controlled, double-blind study.

    Science.gov (United States)

    Erfurt, L; Schandry, R; Rubenbauer, S; Braun, U

    2014-09-25

    The present study investigated the effects of repeated administration of Korodin(®), a combination of camphor and crataegus berry extract, on blood pressure and attentional functioning. This study was conducted based on a randomized, placebo-controlled, double-blind design. 54 persons participated (33 female, 21 male) with a mean age of 24.3 years. Blood pressure and body mass index were in the normal range. Participants received 20 drops of either Korodin(®) or a placebo for four times with interjacent time intervals of about 10 min. Blood pressure was measured sphygmomanometrically before and after each administration. Attentional performance was quantified by using two paper-and-pencil tests, the d2 Test of Attention and Digit Symbol Test. Greater increases in blood pressure occurred after the four Korodin(®) administrations in comparison to the four placebo administrations. The performance in two parameters of d2 Test of Attention was consistently superior after the intake of Korodin(®). The excellent tolerability and safety of Korodin(®), even after a total consumption of 80 drops, was confirmed. Copyright © 2014 Elsevier GmbH. All rights reserved.

  16. Effect of repeated oral administration of Bifidobacterium longum BB536 on apomorphine-induced rearing behavior in mice.

    Science.gov (United States)

    Orikasa, Shuzo; Nabeshima, Kazumi; Iwabuchi, Noriyuki; Xiao, Jin-Zhong

    2016-01-01

    Schizophrenia is a chronic psychiatric illness. Disruption of the dopaminergic system has been suggested to be the pathogenic cause of this disease. The effect of Bifidobacterium longum BB536 (BB536) on schizophrenic behavior was investigated in an animal model. Daily administration of BB536 (10(9) CFU/mouse, p.o. for 2 weeks) was found to reduce rearing behavior augmented by the dopamine receptor agonist apomorphine and to decrease the resting level of plasma corticosterone and the ratio of kynurenine to tryptophan. These results suggest the potential of BB536 for supplemental treatment of the symptoms of schizophrenia.

  17. Informed consent for the administration of an intravenous contrast agent: importance and determinants of patient refusal; Consentimiento informado para la administracion de contraste intravenoso. Importancia y factores determinantes del rechazo por los pacientes

    Energy Technology Data Exchange (ETDEWEB)

    Martel, J. [Fundacion Hospital Alcorcon. Madrid (Spain); Garcia-Diaz, J. D. [Hospital Universitario Principe de Asturias. Alcala de Henares. Madrid (Spain)

    1999-07-01

    We proposed to determine the proportion of patients who refuse to undergo intravenous contrast administration and the factors that influence their refusal. Our series consisted of 442 patients who were supposed to undergo imaging studies involving the intravenous injection of an iodine contrast. In a personal interview, the patients were issued a questionnaire specifically designed for this study. The following parameters were recorded: sex, age, inpatient or outpatient status, medical history available, person who informed them about the procedure, person signing the informed consent (patient or other) , highest academic degree, attitude toward receiving the information and degree of concern after reading and signing the consent form. In our series 8.6% of the patients (95% confidence interval: 6-11.2) refused to sign the informed consent form. In addition, there were a number of patients who delayed the procedure or hindered the daily work schedule by some other means. When the relationship between each of the variables studied and refusal to sign the consent form was assessed, significant associations were observed between the latter and the academic level of the patient, his or her degree of concern and having received the information from a trained person. There was also a nearly significant trend toward the association between refusal and the patient's background. Relatively few patients refuse to sign the informed consent to receive intravenous contrast administration but this negative decision interferes with the health care practice. It is possible to identify certain correctable factors that influence the patient in this respect. (Author) 13 refs.

  18. Loss of phenotype of parvalbumin interneurons in rat prefrontal cortex is involved in antidepressant- and propsychotic-like behaviors following acute and repeated ketamine administration.

    Science.gov (United States)

    Zhou, ZhiQiang; Zhang, GuangFen; Li, XiaoMin; Liu, XiaoYu; Wang, Nan; Qiu, LiLi; Liu, WenXue; Zuo, ZhiYi; Yang, JianJun

    2015-04-01

    Accumulating evidence has demonstrated that single subanesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant-like effects. Nevertheless, repeated subanesthetic doses of ketamine produce psychosis-like effects with dysfunction of parvalbumin (PV) interneurons. We hypothesized that PV interneurons play an important role in the antidepressant-like actions of ketamine, and different changes in PV interneurons occur with the antidepressant-like and propsychotic-like effects of ketamine. To test this hypothesis, ketamine's antidepressant-like effects were evaluated by the forced swimming test. Ketamine-induced stereotyped behaviors and hyperactivity actions and the function of PV interneurons were also assessed. We demonstrated that an acute dose of 10 mg/kg ketamine induced significant antidepressant-like effects and reduced the levels of PV and the gamma-aminobutyric acid (GABA)-producing enzyme GAD67 in the rat prefrontal cortex. Moreover, inhibition of ketamine-induced loss of PV by apocynin blocked these antidepressant-like effects. Repeated administration of 30 mg/kg ketamine elicited stereotyped behaviors and hyperactivity actions as well as a longer duration of PV and GAD67 loss, higher brain glutamate levels, and lower brain GABA levels than acute single dose of ketamine. Our results reveal that the loss of phenotype of PV interneurons in the prefrontal cortex contributes to the antidepressant-like actions and is also involved in the propsychotic-like behaviors following acute and repeated ketamine administration, which may be partially mediated by the disinhibition of glutamate signaling. The different degrees and durations of the actions on PV interneurons produced by the two regimens of ketamine may partly underline the behavioral variance between the antidepressant- and propsychotic-like effects.

  19. Potential resource and cost saving analysis of subcutaneous versus intravenous administration for rituximab in non-Hodgkin's lymphoma and for trastuzumab in breast cancer in 17 Italian hospitals based on a systematic survey

    Directory of Open Access Journals (Sweden)

    Ponzetti C

    2016-05-01

    Full Text Available Clemente Ponzetti,1 Monica Canciani,2 Massimo Farina,2 Sara Era,3 Stefan Walzer4,5 1Group Policlinic Monza, Alessandria, National Scientific Associazione Nazionale dei Medici delle Direzioni Ospedaliere (National Association of Hospital Physicians, Bologna, 2Studio EmmEffe S.r.l, Milan, 3Roche S.p.a., Monza, Italy; 4MArS Market Access and Pricing Strategy GmbH, Weil am Rhein, 5Health Care Management, State University Baden-Wuerttemberg, Loerrach, Germany Introduction: Subcutaneous versions of different oncology therapies have been available for patients for a few years, yet patient-relevant and hospital benefits have not been assessed in real life. Methods: In order to analyze the impact of subcutaneous administrations for rituximab or trastuzumab in comparison to the respective intravenous mode a primary research in Italy was executed. The study’s primary objectives were to analyze the resource and cost implications from different perspectives (patient, medical staff in the real world. The route of administration was discussed and aligned with the participating centers in order to capture all relevant therapy parts. After the successful execution of a pilot study 19 centers in six regions in Italy were recruited to participate. Results: Significant time savings might be achieved with the subcutaneous mode through significantly lower patient preparation time including less time preparing the actual dosing for each individual patient. The total time difference is 3.3 hours with rituximab in hematology (non-Hodgkin’s lymphoma, which adds up to 23.55 hours for a full course of treatment per patient (overall preparation time: 40.1 hours intravenous [95% confidence interval (CI: ±0.47] vs 16.6 hours subcutaneous [95% CI: ±0.2]. In early breast cancer (trastuzumab, the time saving might be 3.3 hours for the first cycle and the total time saving for patient preparation might be 17.2 hours (overall preparation time: 38.8 hours intravenous [95% CI

  20. Pharmacokinetics of enrofloxacin and flunixin meglumine and interactions between both drugs after intravenous co-administration in healthy and endotoxaemic rabbits.

    Science.gov (United States)

    Elmas, Muammer; Yazar, Enver; Uney, Kamil; Er Karabacak, Ayşe; Traş, Bünyamin

    2008-09-01

    The purpose of this study was to determine the pharmacokinetics and possible interactions of enrofloxacin (ENR) and flunixin meglumine (FM) in healthy rabbits and in rabbits where endotoxaemia had been induced by administering Escherichia coli lipopolysaccharide (LPS). Six male adult New Zealand White rabbits were used for the study. In Phase I, FM (2.2 mg/kg) and ENR (5 mg/kg) were given simultaneously as a bolus intravenous (IV) injection to each healthy rabbit. After a washout period, Phase II consisted of purified LPS administered as an IV bolus injection, then FM and ENR. LPS produced statistically significant increases in some serum biochemical concentrations. After the drugs were co-administered, the kinetic parameters of FM were not significantly different in healthy compared to endotoxaemic rabbits. It is concluded that ENR and FM could be co-administered to rabbits to treat endotoxaemia as no negative interaction was observed between the pharmacokinetics of both drugs.

  1. How Cannabis Causes Paranoia: Using the Intravenous Administration of ∆9-Tetrahydrocannabinol (THC) to Identify Key Cognitive Mechanisms Leading to Paranoia

    Science.gov (United States)

    Freeman, Daniel; Dunn, Graham; Murray, Robin M.; Evans, Nicole; Lister, Rachel; Antley, Angus; Slater, Mel; Godlewska, Beata; Cornish, Robert; Williams, Jonathan; Di Simplicio, Martina; Igoumenou, Artemis; Brenneisen, Rudolf; Tunbridge, Elizabeth M.; Harrison, Paul J.; Harmer, Catherine J.; Cowen, Philip; Morrison, Paul D.

    2015-01-01

    Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. The objective was to determine whether the principal psychoactive ingredient of cannabis—∆9-tetrahydrocannabinol (THC)—causes paranoia and to use the drug as a probe to identify key cognitive mechanisms underlying paranoia. A randomized, placebo-controlled, between-groups test of the effects of intravenous THC was conducted. A total of 121 individuals with paranoid ideation were randomized to receive placebo, THC, or THC preceded by a cognitive awareness condition. Paranoia was assessed extensively via a real social situation, an immersive virtual reality experiment, and standard self-report and interviewer measures. Putative causal factors were assessed. Principal components analysis was used to create a composite paranoia score and composite causal variables to be tested in a mediation analysis. THC significantly increased paranoia, negative affect (anxiety, worry, depression, negative thoughts about the self), and a range of anomalous experiences, and reduced working memory capacity. The increase in negative affect and in anomalous experiences fully accounted for the increase in paranoia. Working memory changes did not lead to paranoia. Making participants aware of the effects of THC had little impact. In this largest study of intravenous THC, it was definitively demonstrated that the drug triggers paranoid thoughts in vulnerable individuals. The most likely mechanism of action causing paranoia was the generation of negative affect and anomalous experiences. PMID:25031222

  2. How cannabis causes paranoia: using the intravenous administration of ∆9-tetrahydrocannabinol (THC) to identify key cognitive mechanisms leading to paranoia.

    Science.gov (United States)

    Freeman, Daniel; Dunn, Graham; Murray, Robin M; Evans, Nicole; Lister, Rachel; Antley, Angus; Slater, Mel; Godlewska, Beata; Cornish, Robert; Williams, Jonathan; Di Simplicio, Martina; Igoumenou, Artemis; Brenneisen, Rudolf; Tunbridge, Elizabeth M; Harrison, Paul J; Harmer, Catherine J; Cowen, Philip; Morrison, Paul D

    2015-03-01

    Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. The objective was to determine whether the principal psychoactive ingredient of cannabis-∆(9)-tetrahydrocannabinol (THC)-causes paranoia and to use the drug as a probe to identify key cognitive mechanisms underlying paranoia. A randomized, placebo-controlled, between-groups test of the effects of intravenous THC was conducted. A total of 121 individuals with paranoid ideation were randomized to receive placebo, THC, or THC preceded by a cognitive awareness condition. Paranoia was assessed extensively via a real social situation, an immersive virtual reality experiment, and standard self-report and interviewer measures. Putative causal factors were assessed. Principal components analysis was used to create a composite paranoia score and composite causal variables to be tested in a mediation analysis. THC significantly increased paranoia, negative affect (anxiety, worry, depression, negative thoughts about the self), and a range of anomalous experiences, and reduced working memory capacity. The increase in negative affect and in anomalous experiences fully accounted for the increase in paranoia. Working memory changes did not lead to paranoia. Making participants aware of the effects of THC had little impact. In this largest study of intravenous THC, it was definitively demonstrated that the drug triggers paranoid thoughts in vulnerable individuals. The most likely mechanism of action causing paranoia was the generation of negative affect and anomalous experiences.

  3. Cellular Composition of the Spleen and Changes in Splenic Lysosomes in the Dynamics of Dyslipidemia in Mice Caused by Repeated Administration of Poloxamer 407.

    Science.gov (United States)

    Goncharova, N V; Shurlygina, A V; Mel'nikova, E V; Karmatskikh, O L; Avrorov, P A; Loktev, K V; Korolenko, T A

    2015-11-01

    We studied the effect of dyslipidemia induced by poloxamer 407 (300 mg/kg twice a week for 30 days) on cellular composition of the spleen and splenocyte lysosomes in mice. Changes in blood lipid profile included elevated concentrations of total cholesterol, aterogenic LDL, and triglycerides most pronounced in 24 h after the last poloxamer 407 injection; gradual normalization of lipid profile was observed in 4 days (except triglycerides) and 10 days. The most pronounced changes in the spleen (increase in organ weight and number of cells, inhibition in apoptosis, and reduced accumulation of vital dye acridine orange in lysosomes) were detected on day 4; on day 10, the indices returned to normal. Cathepsin D activity in the spleen also increased at these terms. The relationship between changes in the cellular composition of the spleen and dynamics of serum lipid profile in mice in dyslipidemia caused by repeated administrations of relatively low doses of poloxamer 407 is discussed.

  4. [The main pharmacokinetic parameters of p-tyrosol upon intravenous injection in rats. II. Verification of the pharmacokinetics linearity and evaluation of the possible accumulation].

    Science.gov (United States)

    Chernysheva, G A; Plotnikov, M B; Smol'iakova, V I; Cherkashina, I V; Tolstikova, T G; Krysin, A P; Sorokina, I V

    2006-01-01

    The main pharmacokinetic parameters of p-tyrosol after single (in 3 doses) and repeated intravenous injection were studied in rats. The content ofp-tyrosol in the blood plasma was determined by spectrofluorimetric method. The pharmacokinetic parameters of p-tyrosol are linear in the dose range from 50 to 200 mg/kg. Repeated administration leads to accelerated metabolic elimination of p-tyrosol.

  5. The acute toxicity of Najanajaatra venom (NNAV) by oral and intravenous administration%中华眼镜蛇毒口服和静脉注射单次给药对小鼠毒性作用的比较

    Institute of Scientific and Technical Information of China (English)

    张甜; 薛洁; 王响英; 朱路佳; 孙志红; 秦正红

    2016-01-01

    目的:比较中华眼镜蛇毒(NNAV)经口灌服、静脉注射两种染毒途径的半数致死量(LD50),观察两种染毒途径小鼠的急性中毒症状,寻找可能发生毒性作用的靶器官。方法:小鼠经口灌服、静脉注射NNAV后,测定半数致死量(LD50)。观察14 d内小鼠的活动、体征及死亡情况,并对死亡小鼠和存活14 d小鼠的主要脏器进行病理组织学检查。结果:小鼠经口灌服、静脉注射NNAV的LD50分别为102.3、0.624 mg/kg ,95% CI 84.9~123、0.572~0.680 mg/kg。NNAV经口灌服小鼠中毒症状出现快,喘息、强直性抽搐、呼吸抑制、心衰很快死亡;急性中毒受损器官主要为肺毛细血管充血,局部肺泡间隔增宽伴少量炎性细胞浸润;肝血管充血。NNAV静脉注射小鼠中毒症状为瘫卧、呼吸功能麻痹,心肺功能衰竭而死亡。急性中毒受损器官主要为肺泡腔内及细支气管内有红细胞,血管壁周围有水肿;肝细胞弥漫性肿大,致肝小叶结构不清,肝细胞肿胀,基质稀疏,有的呈气球样变,肝血窦受压变狭或消失。结论:NNAV口服染毒的毒性剂量明显低于静脉注射,二种染毒途径动物急性中毒器官的受损程度也有所不同;NNAV两种染毒途径存活14 d的小鼠其组织病理改变均可恢复。%Objective:To compare the lethal dose 50 (LD50 ) of Najanajaatra venom (NNAV) with two routes of drug administration and to explore the target organs of acute toxicity of NNAV ,and to observe the acute poisoning symptoms of the mice and organ lesions with oral and intravenous administration of NNAV . Methods: Two different modes of drug administration (oral administration and intravenous injection) were used to determine the LD50 .Within 14 of survival time period ,the activities ,signs and death of the mice were observed .Then ,pathology analysis was applied to the main organs of the dead and survival

  6. [Effect of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic, on the bone marrow function of rabbits. (1) Intravenous administration by a single bolus injection].

    Science.gov (United States)

    Tone, H; Kiyosaki, T; Shirai, M

    1986-02-01

    New Zealand White rabbits were treated with (2"R)-4'-O-tetrahydropyranyladriamycin-HCl (THP), a new antitumor antibiotic, by an intravenous bolus injection at a dose of 1, 2 or 4 mg/kg. The peripheral leucocyte counts decreased markedly at doses of 2 and 4 mg/kg 1 to 7 days after injection, and the lymphocytes and neutrophils were affected. The nucleated cell count decreased in the bone marrow. Especially 3 days after injection, remarkable reductions of erythroids and immatured myelocytes were observed, with a subsequent rise of the matured myelocytes ratio in bone marrow cell constituents. These changes resulted in a marked increase of M/E ratio. Doxorubicin also showed an inhibitory effect on the bone marrow function of rabbits but the effect was slightly lower than THP. These changes of bone marrow cells reverted 7 days after injection and the recovery of the reduced peripheral leucocyte was also observed 14 days after injection. Therefore, it can be concluded that THP showed suppressive but reversible effects on the bone marrow function of rabbits.

  7. Intravenous administration of human umbilical cord blood-derived AC133+ endothelial progenitor cells in rat stroke model reduces infarct volume: magnetic resonance imaging and histological findings.

    Science.gov (United States)

    Iskander, Asm; Knight, Robert A; Zhang, Zheng Gang; Ewing, James R; Shankar, Adarsh; Varma, Nadimpalli Ravi S; Bagher-Ebadian, Hassan; Ali, Meser M; Arbab, Ali S; Janic, Branislava

    2013-09-01

    Endothelial progenitor cells (EPCs) hold enormous therapeutic potential for ischemic vascular diseases. Previous studies have indicated that stem/progenitor cells derived from human umbilical cord blood (hUCB) improve functional recovery in stroke models. Here, we examined the effect of hUCB AC133+ EPCs on stroke development and resolution in a middle cerebral artery occlusion (MCAo) rat model. Since the success of cell therapies strongly depends on the ability to monitor in vivo the migration of transplanted cells, we also assessed the capacity of magnetic resonance imaging (MRI) to track in vivo the magnetically labeled cells that were administered. Animals were subjected to transient MCAo and 24 hours later injected intravenously with 10(7) hUCB AC133+ EPCs. MRI performed at days 1, 7, and 14 after the insult showed accumulation of transplanted cells in stroke-affected hemispheres and revealed that stroke volume decreased at a significantly higher rate in cell-treated animals. Immunohistochemistry analysis of brain tissues localized the administered cells in the stroke-affected hemispheres only and indicated that these cells may have significantly affected the magnitude of endogenous proliferation, angiogenesis, and neurogenesis. We conclude that transplanted cells selectively migrated to the ischemic brain parenchyma, where they exerted a therapeutic effect on the extent of tissue damage, regeneration, and time course of stroke resolution.

  8. [Does intravenous gadolinium-DTPA administration have advantages in magnetic resonance imaging of acute injuries or chronic damage to the knee joint?].

    Science.gov (United States)

    Jerosch, J; Castro, W H; Müller, U; Assheuer, J

    1994-12-01

    79 patients with acute or chronic lesions of the knee were evaluated by MRI prior to and after application of Gd-DTPA. The MRI examination was performed by a 1.0 tesla imager with SE as well as FEDIF sequences. These MR studies were compared prior to and after intravenous Gd-DTPA application, focusing on the visibility and the definition of a possible lesion, and scored with a 3-point score. Statistic analysis and case analysis revealed that in patients with meniscus degeneration without a tear, Gd application yields no additional diagnostic information. However, in patients with meniscus tears Gd-DTPA significantly facilitates the definition of the lesion. Furthermore, Gd-DTPA makes differentiation possible between the synovial fluid and the synovial membrane. Whereas in cases with capsule or collateral ligament tears Gd-DTPA facilitates the documentation of the lesion, we found no advantage in using Gd-DPTA in patients with ACL tears. In patients with chondropathia patellae Gd-DTPA application supports the visualization of the secondary synovial reaction.

  9. Behavioural effects of rapid intravenous administration of meta-chlorophenylpiperazine (m-CPP) in patients with generalized social anxiety disorder, panic disorder and healthy controls.

    Science.gov (United States)

    Van Veen, J F; Van der Wee, N J A; Fiselier, J; Van Vliet, I M; Westenberg, H G M

    2007-10-01

    Findings from epidemiological, pharmacotherapeutical, genetic and neurobiological studies suggest a possible overlap in the neurobiology of generalized social anxiety disorder (gSAD) and panic disorder (PD). Previously we have found a rapid intravenous m-CPP challenge of 0.1 mg/kg to be highly sensitive and selective in the provocation of panic attacks in patients with PD. We therefore directly compared the behavioural, neuroendocrine and physiological effects of this rapid m-CPP challenge in a small sample of patients with gSAD, patients with PD and matched healthy controls. Panic attacks were significantly more provoked in patients with PD (85%), but not in patients with gSAD (14%) as compared to healthy controls (0%). Effects on the other behavioural parameters, but not on the neuroendocrine and physiological parameters, were significantly greater in patients with PD compared to patients with gSAD and controls. Our preliminary data do not support a shared neurobiology of gSAD and PD.

  10. Early administration of therapeutic anticoagulation following intravenous thrombolysis for acute cardiogenic embolic stroke caused by left ventricular thrombus: case report and topic review

    Directory of Open Access Journals (Sweden)

    Rick eGill

    2015-02-01

    Full Text Available Cardiogenic cerebral embolism represents 20% of all acute ischemic strokes with one third of these being caused by left ventricular thrombus (LVT. LVT is not a contraindication for treatment with intravenous recombinant tissue plasminogen activator (IV rtPA for acute ischemic stroke (AIS. However the subsequent treatment of a potentially unstable LVT is contraindicated for 24 hours following the use of IV rtPA according to current guidelines. We present a 66-year-old man with AIS treated with IV rtPA. Echocardiogram shortly after treatment demonstrated both a large apical and septal thrombus in the left ventricle and at 12 hours post IV rtPA infusion, therapeutic anticoagulation with heparin was started without complication. In practice, the action of IV rtPA outlasts its apparent half-life because of thrombin-binding and the prolonged effects and longer half-life of its product, plasmin, however the pharmacokinetics do not warrant prolonged avoidance of therapeutic anticoagulation when clinically indicated. Our case demonstrates that anticoagulation for potentially unstable LVT can be safely initiated at 12 hours following IV rtPA treatment for AIS.

  11. Suitability evaluation standards for the administration of intravenous immunoglobulin%临床使用静脉注射免疫球蛋白的适宜性评价标准

    Institute of Scientific and Technical Information of China (English)

    李玥

    2013-01-01

    Objective:To develop the suitability evaluation standards for the administration of intravenous immunoglobulin (IVIG),which would provide sound basis for clinicians to work out proper treatment protocols,and good evidence for clinical pharmacists to make special evaluations on the administration of IVIG.Methods:Through retrieval of current special IVIG guidelines,judgment and comprehensive analysis were made on the inconsistency that might exist,and finally the recommended levels were determined.Results:Recommended categories of IVIG (licensed indications,recommended benefit,discretion benefit more,discretion-benefit less,no support) for the administration,selected indications,dosage and course of treatment etc.were used as the suitability evaluation standards.Conclusion:Operable suitability evaluation standards were established for the administration of IVIG.It could provide good evidence both for clinicians to develop proper treatment protocols and clinical pharmacists to make special evaluations on the administration of IVIG.%目的:制定临床使用静脉注射免疫球蛋白(intravenous immunoglobulin,IVIG)的适宜性评价标准,为临床医师制定治疗方案及临床药师对临床使用IVIG的专项点评提供评价依据.方法:检索国际现有专项IVIG使用指南,对其间存在的不完全一致现象进行判断及综合分析,对其推荐级别进行判定.结果:制定出临床使用IVIG的推荐类别(获准适应证、推荐-获益、酌情-获益多、酌情-获益少、不支持使用)、选用指征、剂量、疗程等作为适宜性评价标准.结论:确立较适宜且可操作性的临床使用IVIG的适宜性评价表,为临床医师制定治疗方案及临床药师对IVIG临床使用专项点评提供评价依据.

  12. Repeated ketamine administration alters N-methyl-d-aspartic acid receptor subunit gene expression: Implication of genetic vulnerability for ketamine abuse and ketamine psychosis in humans

    Science.gov (United States)

    Lipsky, Robert H

    2015-01-01

    For more than 40 years following its approval by the Food and Drug Administration (FDA) as an anesthetic, ketamine, a non-competitive N-methyl-d-aspartic acid (NMDA) receptor antagonist, has been used as a tool of psychiatric research. As a psychedelic drug, ketamine induces psychotic symptoms, cognitive impairment, and mood elevation, which resemble some symptoms of schizophrenia. Recreational use of ketamine has been increasing in recent years. However, little is known of the underlying molecular mechanisms responsible for ketamine-associated psychosis. Recent animal studies have shown that repeated ketamine administration significantly increases NMDA receptor subunit gene expression, in particular subunit 1 (NR1 or GluN1) levels. This results in neurodegeneration, supporting a potential mechanism where up-regulation of NMDA receptors could produce cognitive deficits in chronic ketamine abuse patients. In other studies, NMDA receptor gene variants are associated with addictive behavior. Here, we focus on the roles of NMDA receptor gene subunits in ketamine abuse and ketamine psychosis and propose that full sequencing of NMDA receptor genes may help explain individual vulnerability to ketamine abuse and ketamine-associated psychosis. PMID:25245072

  13. Efficacy Observation of Amiodarone in the Treatment of Atrial Fibrillation Cardioversion with Intravenous Administration%静脉应用胺碘酮治疗心房颤动复律的疗效观察

    Institute of Scientific and Technical Information of China (English)

    张景富; 尹春元

    2011-01-01

    OBJECTIVE: To observe clinical efficacy of amiodarone in the treatment of atrial fibrillation cardioversion with intravenous administration. METHODS: 172 patients with atrial fibrillation were randomly divided into amiodarone group and placebo group. Amiodarone group (n=87) received amiodarone 5 mg·kg-1 intravenously, and then followed by continuous infusion of 0.9% Sodium chloride injection with amiodarone at 10~20 mg·kg-1· d-1 until sinus rhythm was restored. Placebo group (n=85)received0.9% Sodium chloride injection with intravenous push and intravenous infusion, and ventricular rate control treatment. Successful rate and time of rhythm control of 2 groups were observed. RESULTS: 74 patients (85.1%) in amiodarone group returned into sinus rhythm. 68 patients (80.0%) in placebo group also returned into sinus rhythm (P>0.05). The duration of atrial fibrillation in amiodarone group was shorter than in placebo group (P<0.01). One patient suffered from sinus bradycardia in amiodarone group. CONCLUSION: Intravenous administration of amiodarone can not improve the successful rate of rhythm control but can shorten the duration of atrial fibrillation.%目的:观察静脉应用胺碘酮对心房颤动复律的临床疗效.方法:将172例心房颤动患者随机分为胺碘酮组和安慰剂组.胺碘酮组(n=87)静脉推注胺碘酮5mg·kg-1,再以胺碘酮10~20mg·kg-1·d-1加入0.9%氯化钠注射液中持续静脉滴注,维持直至恢复为窦性节律;安慰剂组(n=85)静脉推注和静脉滴注0.9%氯化钠注射液,并给予控制心室率治疗.观察2组复律成功率和复律时间.结果:胺碘酮组有74例(85.1%)恢复为窦性节律,安慰剂组有68例(80.0%)恢复为窦性节律,2组比较差异无统计学意义(P>0.05).胺碘酮组心房颤动持续时间短于安慰剂组(P<0.01).胺碘酮组1例患者出现窦性心动过缓,停药后恢复.结论:胺碘酮静脉应用不能提高复律率,但能缩短心房颤动持续时间.

  14. The efficacy of intravenous administration of sodium valproate for epileptic state%丙戊酸钠静脉滴注治疗癫痫持续状态的疗效分析

    Institute of Scientific and Technical Information of China (English)

    万婷玉; 王丹; 王艳竹; 任庆华; 李孟修

    2013-01-01

    Objective To explore the efficacy and safety of intravenous administration of sodium valproate for epileptic state (SE).Methods 60 patients with SE were randomly divided into a study group and a control group,30 for each group.The study group received a slow intravenous injection of sodium valproate at an initial dose of 15mg/kg for 5 minutes,and then an continuous infusion of 1 mg / (kg.hr) ; while the control group received a slow intravenous injection of diazepam at an initial dose of 10mg for 5 minutes,and then an intravenous drip with mixed solution of diazepam of 100 mg and 0.9% sodium chloride of 500 ml.Results There was no significant difference between the two groups in control cases (P>0.05).The recurrent rate was lower in the study group than in the control group,with a significant statistical difference (P<0.05).Sodium valproate had smaller effects on respiration and consciousness than diazepam,with a significant statistical difference (P<0.05).Conclusions Intravenous administration of sodium valproste is an effective method in the treatment of epileptic state.It has fewer adverse reactions and is worth popularizing clinically.%目的 探讨丙戊酸钠静脉滴注治疗癫痫持续状态(status epilepticus,SE)的有效性及安全性.方法 60例SE患者随机分为治疗组和对照组各30例,治疗组使用丙戊酸钠注射液,首剂以1 5 mg/kg剂量缓慢静脉推注,推注时间5分钟.然后以1 mg/ (kg.hr)的速度静滴.对照组使用地西泮注射液,首剂以10 mg缓慢静脉推注,推注时间5分钟.随后以地西泮100 mg溶于生理盐水500ml中,于12小时内缓慢静脉滴注.结果 两组控制例数差异无统计学意义(P>0.05).治疗组复发率低于对照组,差异具有统计学意义(P<0.05).治疗组对呼吸、意识的影响小,差异具有统计学意义(P<0.05).结论 静脉滴注丙戊酸钠治疗SE是一种有效的方法,不良反应少,值得临床推广应用.

  15. Integrated modelling of the clinical pharmacokinetics of SDZ HTF 919, a novel selective 5-HT4 receptor agonist, following oral and intravenous administration.

    Science.gov (United States)

    Appel-Dingemanse, S; Lemarechal, M O; Kumle, A; Hubert, M; Legangneux, E

    1999-05-01

    The purpose of the present study was to assess the pharmacokinetics of the novel selective 5-HT4 receptor agonist SDZ HTF 919 (HTF) including food effect, absolute bioavailability, interoccasion and intersubject variabilities. In the randomized, open-label, three treatment, four period crossover study, HTF was administered to 12 young healthy male subjects as a 12 mg tablet (twice under fasted and once under fed conditions) and a 3 mg intravenous (i.v.) infusion over 40 min (fasted). Pharmacokinetic parameters were obtained by noncompartmental methods. A more comprehensive pharmacokinetic characterization was achieved by integrated modelling of oral (p.o.) and i.v. data. To describe the absorption phase a Weibull function and a classical first order input function were compared. Noncompartmental pharmacokinetic analysis revealed a rapid absorption (tmax 1.3 h, fasted), an absolute bioavailability of 11+/-3%, a biphasic disposition phase with a terminal half-life of 11+/-5 h, a clearance of 77+/-15 l h-1, and a volume of distribution at steady state of 368+/-223 l. The coefficients of interoccasion and interindividual variability in Cmax and AUC ranged between 17 and 28%. Food intake caused a delay (tmax 2.0 h) and decrease in absorption with consequently lower systemic exposure ( approximately 5% absolute bioavailability). Integrated p.o./i.v. pharmacokinetic modelling with a Weibull input function allowed accurate description of individual profiles. Modelling of the data from the p.o. dosing improved the description of the terminal phase by inclusion of the i. v. data and additionally provided quantitative characterization of the absorption phase. The pharmacokinetics of HTF could be well described by an integrated modelling approach for both p.o. and i.v. data. The derived model will provide guidance in the design of future studies.

  16. Cardiovascular responses to intravenous administration of human hemokinin-1 and its truncated form hemokinin-1(4-11) in anesthetized rats.

    Science.gov (United States)

    Kong, Zi-Qing; Fu, Cai-Yun; Chen, Qiang; Wang, Rui

    2008-08-20

    Human hemokinin-1 and its carboxy-terminal fragment human hemokinin-1(4-11) have been recently identified as the members of the tachykinin family. The peripheral cardiovascular effects of these two tachykinin peptides were investigated in anesthetized rats. Lower doses of human hemokinin-1 (0.1-3 nmol/kg) injected intravenously (i.v.) induced depressor response, whereas higher doses (10 and 30 nmol/kg) caused biphasic (depressor and pressor) responses. The depressor response is primarily due to the action on endothelial tachykinin NK(1) receptor to release endothelium-derived relaxing factor (NO) and vagal reflex was absent in this modulation. The pressor response is mediated through the activation of tachykinin NK(1) receptor to release catecholamines from sympathetic ganglia and adrenal medulla. Moreover, human hemokinin-1 injected i.v. produced a dose-dependent tachycardia response along with blood pressure responses and the activation of sympathetic ganglia and adrenal medulla are involved in the tachycardia response. Human hemokinin-1(4-11) only lowered mean arterial pressure dose-dependently (0.1-30 nmol/kg) and the mechanisms involved in the depressor response are similar to that of human hemokinin-1. Additionally, human hemokinin-1(4-11) could also produce tachycardia response dose-dependently and the mechanisms involved in the tachycardia response are similar to that of human hemokinin-1 except that bilateral adrenalectomy could not affect the tachycardia markedly, indicating that the tachycardia induced by human hemokinin-1(4-11) is primarily due to the stimulation of sympathetic ganglia. In a word, to a certain extent, human hemokinin-1(4-11) is the active fragment of human hemokinin-1, however, the differences between human hemokinin-1 and hemokinin-1(4-11) involved in the effects of cardiovascular system suggest that the divergent amino acid residues at the N-terminus of human hemokinin-1 produced different activation properties for tachykinin NK(1

  17. Effect of preoperative administration of intravenous paracetamol during cesarean surgery on hemodynamic variables relative to intubation, postoperative pain and neonatal apgar.

    Science.gov (United States)

    Ayatollahi, Vida; Faghihi, Safa; Behdad, Shokoufeh; Heiranizadeh, Najmeh; Baghianimoghadam, Behnam

    2014-09-01

    Selection of anesthetic drugs for cesarean section requires many considerations. Anesthetic drugs for this purpose must prevent hemodynamic stress due to tracheal intubation, while inducing neonatal complications. This study was conducted to determine the effects of paracetamol given before induction of anesthesia on cardiovascular responses to tracheal intubation and postoperative pain in the mother, and on neonatal Apgar score. This double-blind randomized placebo-controlled trial included 60 women in ASA I, without underlying diseases and fetal distress, who were candidates for elective cesarean section under general anesthesia. Patients were divided into two groups of 30 patients. Patients in the paracetamol group received 1 g intravenous (IV) paracetamol 20 min before the operation, while those in the placebo group received 1 cc normal saline at the same time. In both groups, anesthesia was induced by sodium thiopental and succinylcholine. Maternal systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were measured before and immediately upon induction of anesthesia, and at first and fifth minute after tracheal intubation. Neonatal effects were assessed by Apgar score. Postoperative pain was assessed by use of the visual analog scale (VAS). The dose of analgesic used and the time of the first analgesic request by patients postoperatively were recorded. The SBP, DBP, MAP and HR were controlled significantly better in paracetamol group than in placebo group (P neonates did not differ between the groups. The VAS pain score was significantly lower in paracetamol group than in placebo group at all measuring times (P pain postoperatively (P pain management without considerable neonatal complications in women undergoing cesarean section in general anesthesia.

  18. Effect of External Pressure and Catheter Gauge on Flow Rate, Kinetic Energy, and Endothelial Injury During Intravenous Fluid Administration in a Rabbit Model.

    Science.gov (United States)

    Hu, Mei-Hua; Chan, Wei-Hung; Chen, Yao-Chang; Cherng, Chen-Hwan; Lin, Chih-Kung; Tsai, Chien-Sung; Chou, Yu-Ching; Huang, Go-Shine

    2016-01-01

    The effects of intravenous (IV) catheter gauge and pressurization of IV fluid (IVF) bags on fluid flow rate have been studied. However, the pressure needed to achieve a flow rate equivalent to that of a 16 gauge (G) catheter through smaller G catheters and the potential for endothelial damage from the increased kinetic energy produced by higher pressurization are unclear. Constant pressure on an IVF bag was maintained by an automatic adjustable pneumatic pressure regulator of our own design. Fluids running through 16 G, 18 G, 20 G, and 22 G catheters were assessed while using IV bag pressurization to achieve the flow rate equivalent to that of a 16 G catheter. We assessed flow rates, kinetic energy, and flow injury to rabbit inferior vena cava endothelium. By applying sufficient external constant pressure to an IVF bag, all fluids could be run through smaller (G) catheters at the flow rate in a 16 G catheter. However, the kinetic energy increased significantly as the catheter G increased. Damage to the venous endothelium was negligible or minimal/patchy cell loss. We designed a new rapid infusion system, which provides a constant pressure that compresses the fluid volume until it is free from visible residual fluid. When large-bore venous access cannot be obtained, multiple smaller catheters, external pressure, or both should be considered. However, caution should be exercised when fluid pressurized to reach a flow rate equivalent to that in a 16 G catheter is run through a smaller G catheter because of the profound increase in kinetic energy that can lead to venous endothelium injury.

  19. Pharmacokinetics and tissue distribution after intravenous administration of a single dose of amphotericin B cochleates, a new lipid-based delivery system.

    Science.gov (United States)

    Segarra, Ignacio; Movshin, Diane A; Zarif, Leila

    2002-08-01

    Model independent pharmacokinetic analysis of intravenous (iv) amphotericin B cochleates (CAMB), a new lipid-based drug delivery system, in mice (0.625 mg/kg) shows a two-phase disposition profile in blood [area under the curve of concentration versus time from time zero to infinity (AUC(0-infinity)) = 1.01 microg. h/mL, half-life (t((1/2))) = 11.68 h, volume of distribution at steady state (V(ss)) = 9.59 L/kg, clearance (CL) = 10.36 mL/min/kg and mean residence time from time 0 to infinity (MRT(0-infinity)) = 15.41 h). In target tissues, maximum time (t(max)) ranged from 2 min (spleen and lung) to 10 min (liver) and lungs presented the highest AMB concentration (16.4 microg. h/g) followed by liver (8.56 microg/g), and spleen (6.63 microg/g). In addition, liver and spleen presented the longest elution half-life (75.03 and 66.71 h, respectively), MRT(0-infinity) (98.4 and 86.3 h, respectively), and AMB exposure:liver AUC(0-infinity) = 474 and 116.4 microg. h/g for the spleen. The large V(ss) and the extensive tissue AUC indicate large and efficient ability of cochleates to penetrate and deliver AMB. Differences in tissue uptake mechanism and pharmacokinetic data suggest a crucial role of macrophages in CAMB clearance from blood as well as an essential role of the liver and the spleen in AMB distribution to target tissues.

  20. Tritium excretion after intravenous administration of tritium labelled adrenaline and noradrenaline and digital vascular reactivity to adrenaline and noradrenaline in normotensive and labile hypertensive subjects.

    Science.gov (United States)

    De Guia, D; Mendlowitz, M; Vlachakis, N D; Gitlow, S E; Nissenbaum, M

    1980-01-01

    1. The 24-h urinary excretion of tritium after tritiated adrenaline administration and digital vascular reactivity to exogenously administered adrenaline and noradrenaline were measured in ten normotensive and in twenty-eight labile essential hypertensive subjects. Tritiated noradrenaline excretion and apparent noradrenaline secretion rate were also measured in ten and eleven of these subjects, respectively. 2. Despite overlapping, the mean 24-h tritium excretion after 3H-adrenaline administration as well as reactivity to adrenaline were significantly greater in the hypertensive than in the normotensive subjects, whether or not they had increased responsiveness to noradrenaline. Significant correlation, however, was observed between tritium excretion of adrenaline and reactivity to adrenaline in both labile hypertensive and normotensive subjects. These measurements were also both significantly correlated with percentage variability in systolic and diastolic blood pressure in the labile hypertensive subjects. 3. No significant correlation was observed between adrenaline as against noradrenaline measurements, whether physiological or biochemical, in either hypertensive or normotensive subjects.

  1. Comparison of self-administration behavior and responsiveness to drug-paired cues in rats running an alley for intravenous heroin and cocaine

    OpenAIRE

    Su, Zu-In; Wenzel, Jennifer; Baird, Rebeccah; Ettenberg, Aaron

    2010-01-01

    Rationale Evidence suggests that responsiveness to a drug-paired cue is predicted by the reinforcing magnitude of the drug during prior self-administration. It remains unclear, however, if this principle holds true when comparisons are made across drug reinforcers. Objective The current study was therefore devised to test the hypothesis that differences in the animals’ responsiveness to a cocaine- or heroin-paired cue presented during extinction would reflect differences in the patterns of pr...

  2. 替罗非班治疗急性心肌梗死的疗效和安全性观察%Efficiency and safety for intravenously administration of urokinase and tirofiban in treating acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    干志红; 苟华良; 孙向阳

    2012-01-01

    目的 观察替罗非班治疗急性心肌梗死(AMI)与尿激酶静脉溶栓合用的安全性及疗效.方法 对122例AMI患者随机分为治疗组60例,对照组62例.两组患者均给予静脉溶栓、硝酸甘油、培哚普利/或氯沙坦、美托洛尔、拜阿司匹林、氯吡格雷、阿托伐他汀钙、依诺肝素等作为基础治疗.治疗组在溶栓后静脉泵入替罗非班,先0.4μg/(kg·min)× 30min,后0.15μg/(kg·min).观察梗死血管再通、出血并发症、主要心脏不良事件(MACE).结果 梗死血管再通率治疗组比对照组显著提高,P<0.05,差异有统计学意义.出血并发症两组无统计学意义,P>0.05.MACE治疗组比对照组显著降低,差异有统计学意义(P<0.05).结论 替罗非班在治疗AMI与尿激酶静脉溶栓合用是安全有效的.%To assess the efficiency and safety for intravenously administration of urokinase and tirofiban for the treatment of acute myocardial infarction. Methods 122 patients with acute myocardial infarction were randomly divided into two groups. 60 were in tirofiban group and 62 in basic therapy group. Patients in both groups took intravenous thrombolysis together with nitroglycerine, perindopril or losartan, metoprolol, aspirin, clopidogrel, atorvastatin calcium, enoxaparin etc. as basic medication. For patients in tirofiban group, tirofiban was additionally administrated by intravenous micro-pump with 0.4μg/(kg·min) for 30 minutes and 0.15μg/(kg·min) for maintenance after thrombolysis. Development of infarction related artery refu-sion, hemorrhage and major adverse cardiac events were observed and recorded. Results The infarction related artery refusion rate in tirofiban group was significantly higher than basic therapy group (P>0.05). There was no major difference in the incidence of hemorrhage between two groups (P<0.05). The development of major adverse cardiac events was significantly lower in tirofiban group than basic therapy group (P <0

  3. The acceptability of repeat Internet-based hybrid diet assessment of previous 24-h dietary intake: administration of the Oxford WebQ in UK Biobank.

    Science.gov (United States)

    Galante, Julieta; Adamska, Ligia; Young, Alan; Young, Heather; Littlejohns, Thomas J; Gallacher, John; Allen, Naomi

    2016-02-28

    Although dietary intake over a single 24-h period may be atypical of an individual's habitual pattern, multiple 24-h dietary assessments can be representative of habitual intake and help in assessing seasonal variation. Web-based questionnaires are convenient for the participant and result in automatic data capture for study investigators. This study reports on the acceptability of repeated web-based administration of the Oxford WebQ--a 24-h recall of frequency from a set food list suitable for self-completion from which energy and nutrient values can be automatically generated. As part of the UK Biobank study, four invitations to complete the Oxford WebQ were sent by email over a 16-month period. Overall, 176 012 (53% of those invited) participants completed the online version of the Oxford WebQ at least once and 66% completed it more than once, although only 16% completed it on all four occasions. The response rate for any one round of invitations varied between 34 and 26%. On most occasions, the Oxford WebQ was completed on the same day that they received the invitation, although this was less likely if sent on a weekend. Participants who completed the Oxford WebQ tended to be white, female, slightly older, less deprived and more educated, which is typical of health-conscious volunteer-based studies. These findings provide preliminary evidence to suggest that repeated 24-h dietary assessment via the Internet is acceptable to the public and a feasible strategy for large population-based studies.

  4. A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia

    Science.gov (United States)

    Quintana-Díaz, Manuel; Fabra-Cadenas, Sara; Gómez-Ramírez, Susana; Martínez-Virto, Ana; García-Erce, José A.; Muñoz, Manuel

    2016-01-01

    Background Clinically significant anaemia, requiring red blood cell transfusions, is frequently observed in Emergency Departments (ED). To optimise blood product use, we developed a clinical protocol for the management of iron-deficiency anaemia in a fast-track anaemia clinic within the ED. Materials and methods From November 2010 to January 2014, patients presenting with sub-acute, moderate-to-severe anaemia (haemoglobin [Hb] <11 g/dL) and confirmed or suspected iron deficiency were referred to the fast-track anaemia clinic. Those with absolute or functional iron deficiency were given intravenous (IV) ferric carboxymaltose 500–1,000 mg/week and were reassessed 4 weeks after receiving the total iron dose. The primary study outcome was the haematological response (Hb≥12 g/dL and/or Hb increment ≥2 g/dL). Changes in blood and iron parameters, transfusion rates and IV iron-related adverse drug effects were secondary outcomes. Results Two hundred and two anaemic patients with iron deficiency (150 women/52 men; mean age, 64 years) were managed in the fast-track anaemia clinic, and received a median IV iron dose of 1,500 mg (1,000–2,000 mg). Gastro-intestinal (44%) or gynaecological (26%) bleeding was the most frequent cause of the anaemia. At follow-up (183 patients), the mean Hb increment was 3.9±2.2 g/dL; 84% of patients were classified as responders and blood and iron parameters normalised in 90%. During follow-up, 35 (17%) patients needed transfusions (2 [range: 1–3] units per patient) because they had low Hb levels, symptoms of anaemia and/or were at risk. Eight mild and one moderate, self-limited adverse drug effects were witnessed. Discussion Our data support the feasibility of a clinical protocol for management of sub-acute anaemia with IV iron in the ED. IV iron was efficacious, safe and well tolerated. Early management of anaemia will improve the use of blood products in the ED. PMID:26674819

  5. Extensive neuroadaptive changes in cortical gene-transcript expressions of the glutamate system in response to repeated intermittent MDMA administration in adolescent rats

    Directory of Open Access Journals (Sweden)

    Malki Rana

    2008-04-01

    Full Text Available Abstract Background Many studies have focused on the implication of the serotonin and dopamine systems in neuroadaptive responses to the recreational drug 3,4-methylenedioxy-metamphetamine (MDMA. Less attention has been given to the major excitatory neurotransmitter glutamate known to be implicated in schizophrenia and drug addiction. The aim of the present study was to investigate the effect of repeated intermittent MDMA administration upon gene-transcript expression of the glutamate transporters (EAAT1, EAAT2-1, EAAT2-2, the glutamate receptor subunits of AMPA (GluR1, GluR2, GluR3, the glutamate receptor subunits of NMDA (NR1, NR2A and NR2B, as well as metabotropic glutamate receptors (mGluR1, mGluR2, mGluR3, mGluR5 in six different brain regions. Adolescent male Sprague Dawley rats received MDMA at the doses of 3 × 1 and 3 × 5 mg/kg/day, or 3× vehicle 3 hours apart, every 7th day for 4 weeks. The gene-transcript levels were assessed using real-time PCR validated with a range of housekeeping genes. Results The findings showed pronounced enhancements in gene-transcript expression of GluR2, mGluR1, mGluR5, NR1, NR2A, NR2B, EAAT1, and EAAT2-2 in the cortex at bregma +1.6. In the caudate putamen, mRNA levels of GluR3, NR2A, and NR2B receptor subunits were significantly increased. In contrast, the gene-transcript expression of GluR1 was reduced in the hippocampus. In the hypothalamus, there was a significant increase of GluR1, GluR3, mGluR1, and mGluR3 gene-transcript expressions. Conclusion Repeated intermittent MDMA administration induces neuroadaptive changes in gene-transcript expressions of glutamatergic NMDA and AMPA receptor subunits, metabotropic receptors and transporters in regions of the brain regulating reward-related associative learning, cognition, and memory and neuro-endocrine functions.

  6. Modelling Framework and Assistive Device for Peripheral Intravenous Injections

    Science.gov (United States)

    Kam, Kin F.; Robinson, Martin P.; Gilbert, Mathew A.; Pelah, Adar

    2016-02-01

    Intravenous access for blood sampling or drug administration that requires peripheral venepuncture is perhaps the most common invasive procedure practiced in hospitals, clinics and general practice surgeries.We describe an idealised mathematical framework for modelling the dynamics of the peripheral venepuncture process. Basic assumptions of the model are confirmed through motion analysis of needle trajectories during venepuncture, taken from video recordings of a skilled practitioner injecting into a practice kit. The framework is also applied to the design and construction of a proposed device for accurate needle guidance during venepuncture administration, assessed as consistent and repeatable in application and does not lead to over puncture. The study provides insights into the ubiquitous peripheral venepuncture process and may contribute to applications in training and in the design of new devices, including for use in robotic automation.

  7. Metabolism and plasma pharmacokinetics of isoorientin, a natural active ingredient, in Sprague-Dawley male rats after oral and intravenous administration.

    Science.gov (United States)

    Shi, Peiying; Lin, Xinhua; Yao, Hong

    2015-01-01

    1. Several pharmacological effects have been revealed on isoorientin, suggesting its potential medicinal prospects. The metabolic and plasma pharmacokinetic profiles of isoorientin were investigated in rats. 2. For intra-gastric gavage, parent drug and three metabolites were detected in urine and feces by HPLC-MS/MS, but only one metabolite was found in plasma and identified as isoorientin 3'- or 4'-O-sulfate (M1) according to MS and UV absorbance spectra. 3. After a single i.v. administration of isoorientin (5, 10, or 15 mg/kg B.W.) in rats, linear pharmacokinetic property was observed with favorable terminal half-lives (1.67 ± 1.32-2.07 ± 0.50 h). After a single p.o. administration of isoorientin (150 mg/kg B.W.) in rats, plasma isoorientin concentration was low, but the concentration of M1 was comparatively high. Low systemic exposure of oral isoorientin in rats could result from its low aqueous solubility and extensive first-pass metabolism, and plasma concentration of M1 can be used as a biomarker of isoorientin intake. Isoorientin showed low oral bioavailability (8.98 ± 1.07%), and had about 6% or 45% dose recovery in urine or feces, respectively, 72 h after intra-gastric gavage. 4. These studies are the first to describe the pharmacokinetics of isoorientin via i.v. or p.o. dosing, providing important information for understanding its process in vivo.

  8. The effect of repeated administrations of llama ovulation-inducing factor (OIF/NGF) during the peri-ovulatory period on corpus luteum development and function in llamas.

    Science.gov (United States)

    Fernández, A; Ulloa-Leal, C; Silva, M; Norambuena, C; Adams, G P; Guerra, M; Ratto, M H

    2014-10-01

    The objective of the study was to test the hypothesis that repeated administrations of OIF/NGF during the peri-ovulatory period (pre-ovulatory, ovulatory, early post-ovulatory), will enhance the luteotrophic effect in llamas. Female llamas were examined daily by transrectal ultrasonography in B- and Doppler-mode using a scanner equipped with a 7.5-MHz linear-array transducer to monitor ovarian follicle and luteal dynamics. When a growing follicle ≥7mm was detected, llamas were assigned randomly to one of the three groups and given 1mg of purified OIF/NGF im (intramuscular) (a) pre-ovulation (single dose; n=12), (b) pre-ovulation and at the time of ovulation (2 doses, n=10), or (c) pre-ovulation, at the time of ovulation, and 24h after ovulation (3 doses, n=10). The pre-ovulatory follicle diameter at the time of treatment, ovulation rate and the first day of CL detection did not differ (P=0.3) among groups. However, maximum CL diameter was greatest (P=0.003) in llamas in the 2-dose group, and smallest in the 3-dose group. Accordingly, the 2 dose-group had the largest day-to-day profile for CL diameter (Pllama seminal plasma is luteotrophic and the effect on CL size and function is affected by the number and timing of treatments during the peri-ovulatory period.

  9. An In Vivo Evaluation of the Effect of Repeated Administration and Clearance of Targeted Contrast Agents on Molecular Imaging Signal Enhancement

    Directory of Open Access Journals (Sweden)

    Jason E. Streeter, Paul A. Dayton

    2013-01-01

    Full Text Available Competitive inhibition diminishes ligand adhesion as receptor sites become occupied with competing ligands. It is unknown if this effect occurs in ultrasound molecular imaging studies where endothelial binding sites become occupied with adherent bubbles or bubble fragments. The goal of this pilot study was to assess the effect that repeated administration and clearance of targeted agents has on successive adhesion. Two groups of animals were imaged with 3-D ultrasonic molecular imaging. Injections and imaging were performed on Group 1 at time 0 and 60 minutes. Group 2 received injections of microbubbles at 0, 15, 30, 45 and 60 minutes with imaging at 0 and 60 minutes. At 60 minutes, Group 1 targeting relative to baseline was not significantly different from Group 2 (1.06±0.27 vs. 1.08±0.34, p=0.93. Data suggest that multiple injections of targeted microbubbles do not block sufficient binding sites to bias molecular imaging data in serial studies.

  10. Safety and Traceability in Patient Healthcare through the Integration of RFID Technology for Intravenous Mixtures in the Prescription-Validation-Elaboration-Dispensation-Administration Circuit to Day Hospital Patients

    Directory of Open Access Journals (Sweden)

    María Martínez Pérez

    2016-07-01

    Full Text Available This work presents the integration of the RFID technology with the aim of ensuring the traceability of patients and minimization of adverse events during the process of prescription-validation-elaboration-dispensation-administration of medication by means of the implementation of various passive and active WIFI RFID systems in the Pharmacy and Day Hospital services of the Complejo Hospitalario Universitario A Coruña. Obtaining patient traceability and using the patient/drug binomial during this process allows us to minimize the occurrence of adverse events. The key points in this work are the unmistakably unique identification and accurate real time location of the controlled items (patients and medication. RFID technology has proved to be invaluable in assisting with the everyday clinical practice of a hospital, and has been successfully implemented in this environment and others. In services such as the day hospital, the implementation of said technology is further justified by the high costs of the service and the high risk to the patient.

  11. Safety and Traceability in Patient Healthcare through the Integration of RFID Technology for Intravenous Mixtures in the Prescription-Validation-Elaboration-Dispensation-Administration Circuit to Day Hospital Patients

    Science.gov (United States)

    Martínez Pérez, María; Vázquez González, Guillermo; Dafonte, Carlos

    2016-01-01

    This work presents the integration of the RFID technology with the aim of ensuring the traceability of patients and minimization of adverse events during the process of prescription-validation-elaboration-dispensation-administration of medication by means of the implementation of various passive and active WIFI RFID systems in the Pharmacy and Day Hospital services of the Complejo Hospitalario Universitario A Coruña. Obtaining patient traceability and using the patient/drug binomial during this process allows us to minimize the occurrence of adverse events. The key points in this work are the unmistakably unique identification and accurate real time location of the controlled items (patients and medication). RFID technology has proved to be invaluable in assisting with the everyday clinical practice of a hospital, and has been successfully implemented in this environment and others. In services such as the day hospital, the implementation of said technology is further justified by the high costs of the service and the high risk to the patient. PMID:27483269

  12. Safety and Traceability in Patient Healthcare through the Integration of RFID Technology for Intravenous Mixtures in the Prescription-Validation-Elaboration-Dispensation-Administration Circuit to Day Hospital Patients.

    Science.gov (United States)

    Martínez Pérez, María; Vázquez González, Guillermo; Dafonte, Carlos

    2016-07-28

    This work presents the integration of the RFID technology with the aim of ensuring the traceability of patients and minimization of adverse events during the process of prescription-validation-elaboration-dispensation-administration of medication by means of the implementation of various passive and active WIFI RFID systems in the Pharmacy and Day Hospital services of the Complejo Hospitalario Universitario A Coruña. Obtaining patient traceability and using the patient/drug binomial during this process allows us to minimize the occurrence of adverse events. The key points in this work are the unmistakably unique identification and accurate real time location of the controlled items (patients and medication). RFID technology has proved to be invaluable in assisting with the everyday clinical practice of a hospital, and has been successfully implemented in this environment and others. In services such as the day hospital, the implementation of said technology is further justified by the high costs of the service and the high risk to the patient.

  13. Plasma and interstitial fluid pharmacokinetics of enrofloxacin, its metabolite ciprofloxacin, and marbofloxacin after oral administration and a constant rate intravenous infusion in dogs.

    Science.gov (United States)

    Bidgood, T L; Papich, M G

    2005-08-01

    Enrofloxacin and marbofloxacin were administered to six healthy dogs in separate crossover experiments as a single oral dose (5 mg/kg) and as a constant rate IV infusion (1.24 and 0.12 mg/h.kg, respectively) following a loading dose (4.47 and 2 mg/kg, respectively) to achieve a steady-state concentration of approximately 1 microg/mL for 8 h. Interstitial fluid (ISF) was collected with an in vivo ultrafiltration device at the same time period as plasma to measure protein unbound drug concentrations at the tissue site and assess the dynamics of drug distribution. Plasma and ISF were analyzed for enrofloxacin, its active metabolite ciprofloxacin, and for marbofloxacin by high performance liquid chromatography (HPLC). Lipophilicity and protein binding of enrofloxacin were higher than for marbofloxacin and ciprofloxacin. Compared to enrofloxacin, marbofloxacin had a longer half-life, higher Cmax, and larger AUC(0-infinity) in plasma and ISF after oral administration. Establishing steady state allowed an assessment of the dynamics of drug concentrations between plasma and ISF. The ISF and plasma-unbound concentrations were similar during the steady-state period despite differences in lipophilicity and pharmacokinetic parameters of the drugs.

  14. Effects of acute intravenous administration of pentamidine, a typical hERG-trafficking inhibitor, on the cardiac repolarization process of halothane-anesthetized dogs.

    Science.gov (United States)

    Yokoyama, Hirofumi; Nakamura, Yuji; Iwasaki, Hiroshi; Nagayama, Yukitoshi; Hoshiai, Kiyotaka; Mitsumori, Yoshitaka; Sugiyama, Atsushi

    2009-08-01

    Although acute treatment of pentamidine does not directly modify any ionic channel function in the heart at clinically relevant concentrations, its continuous exposure can prolong QT interval. Recent in vitro studies have indicated that hERG trafficking inhibition may play an important role in the onset of pentamidine-induced long QT syndrome. In this study, we examined acute in vivo electropharmacological effects of pentamidine using the halothane-anesthetized canine model (n = 5). The clinically relevant total dose of 4 mg/kg of pentamidine (namely, 1 mg/kg, i.v. over 10 min followed by 3 mg/kg, i.v. over 10 min with a pause of 20 min) decreased the mean blood pressure, ventricular contraction, preload to the left ventricle, and peripheral vascular resistance. Pentamidine also enhanced the atrioventricular conduction in parallel with its cardiohemodynamic actions, but it gradually prolonged both the ventricular repolarization period and effective refractory period, whereas no significant change was detected in the intraventricular conduction. Thus, acute administration of a clinically relevant dose of pentamidine can suppress cardiac function and vascular tone with reflex-mediated increase of sympathetic activity, whereas it may delay the repolarization process, suggesting that inhibition of potassium-channel trafficking might be induced more acutely in vivo than those previously expected in vitro.

  15. Increased tumor necrosis factor-alpha and nitric oxide production by rat macrophages following in vitro stimulation and intravenous administration of the delta-opioid agonist SNC 80.

    Science.gov (United States)

    Gomez-Flores, R; Rice, K C; Zhang, X; Weber, R J

    2001-05-04

    Opioids alter immune function by binding to opioid receptors on cells of the immune system, or indirectly by acting on receptors within the central nervous system. Mu-selective opioid agonists are generally associated with immunosuppression, whereas delta-opioid receptor-selective agonists are commonly associated with immunopotentiation. We have previously shown that intracerebroventricular administration of the nonpeptide delta-opioid receptor agonist (+)-4-((alpha R)-alpha-((2S, 5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N, N-diethyl-benzamide (SNC 80) did not alter certain parameters of immunocompetence. In the present study, we studied the in vitro and ex vivo effects of SNC 80 on rat macrophage and lymphocyte functions. We showed that SNC 80 at concentrations of 10(-7) M and 10(-6) M, significantly (P SNC 80 (6.8 mg/kg) significantly (P SNC 80 plus Con A potentiated ex vivo LPS-stimulated macrophage functions. SNC 80 could potentially be utilized in various clinical situations where immunosuppression is undesirable.

  16. Peripheral intravenous line (image)

    Science.gov (United States)

    A peripheral intravenous line is a small, short plastic catheter that is placed through the skin into a vein, ... or foot, but occasionally in the head. A peripheral intravenous line is used to give fluids and ...

  17. Improving Drug Administration to Reduce Drug Use Error Rare of Pharmacy Intravenous Admixture Service%完善药品管理降低静脉用药调配中心药品使用差错率

    Institute of Scientific and Technical Information of China (English)

    周璐; 陈海燕

    2015-01-01

    Objective To reduce drug using error rare of pharmacy intravenous admixture service (PIVAS) by improving drug administration. Methods Drug using errors in PIVAS from March 2014 to August in 2014 were analyzed retrospective-ly, and during this time some measures about drug administration were taken. Results Drug using errors were decreased from 162 cases in March to 39 cases in August in 2014,and the drug using error rate was reduced from 2.04‰to 0.48‰(P<0.05). Conclusion Drug administration played a vital operation in PIVAS, and improving drug management can not only reduce the error rate in PIVAS but also reduce medical risks.%目的 完善药品管理,降低儿童医院静脉用药调配中心(PIVAS)药品使用差错率.方法 回顾该院PIVAS2014年3月-2014年8月,分析完善药品管理前后,药品使用差错的变化情况. 结果 药品使用差错由2014年3月的162例减少为8月的39例,药品使用差错率由2.04‰降为0.48‰(P<0.05). 结论 药品管理在PIVAS运行中起着至关重要的作用,做好药品管理,可降低PIVAS差错率,减少医疗隐患.

  18. Efficacy of intravenous administration of hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses.

    Science.gov (United States)

    Frisbie, David D; McIlwraith, C Wayne; Kawcak, Christopher E; Werpy, Natasha M

    2016-10-01

    OBJECTIVE To evaluate the efficacy of IV administration of a product containing hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses. ANIMALS 32 healthy 2- to 5-year-old horses. PROCEDURES The study involved 2 portions. To evaluate prophylactic efficacy of the test product, horses received 5 mL of the product (n = 8) or saline (0.9% NaCl) solution (8; placebo) IV every fifth day, starting on day 0 (when osteoarthritis was induced in the middle carpal joint of 1 forelimb) and ending on day 70. To evaluate treatment efficacy, horses received either the product or placebo (n = 8/treatment) on days 16, 23, 30, 37, and 44 after osteoarthritis induction. Clinical, diagnostic imaging, synovial fluid, gross anatomic, and histologic evaluations and other tests were performed. Results of each study portion were compared between treatment groups. RESULTS Limb flexion and radiographic findings were significantly worse for horses that received the test product in the prophylactic efficacy portion than for placebo-treated horses or product-treated horses in the treatment efficacy portion. In the prophylactic efficacy portion, significantly less articular cartilage erosion was identified in product-treated versus placebo-treated horses. In the treatment efficacy portion, joints of product-treated horses had a greater degree of bone edema identified via MRI than did joints of placebo-treated horses but fewer microscopic articular cartilage abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that caution should be used when administering the evaluated product IV to horses, particularly when administering it prophylactically, as it may have no benefit or may even cause harm.

  19. Administración oral de preparado parenteral de vitamina K en anticoagulación excesiva por warfarina Oral administration of intravenous preparation of Vitamin K for excessive anticoagulation due to warfarin

    Directory of Open Access Journals (Sweden)

    Yoleima Lozada

    2012-04-01

    Full Text Available La warfarina es frecuentemente usada en la terapia anticoagulante actual, su acción debe ser monitorizada usando el tiempo de protrombina expresado como International Normalized Ratio (INR; cuando se excede el rango de seguridad se puede administrar vitamina K (Vit-K, preferentemente por vía oral. Dicha presentación no está disponible en Venezuela. Se realizó un ensayo clínico, doble ciego, donde a 20 pacientes, edad 18-60 años, sin sangrado e INR inicial de 6 a 10 inclusive; les fue suspendida la warfarina e inmediatamente agrupados al azar a recibir dosis única de Vit-K (oral 1.25mg de Vit-K fraccionada de una presentación parenteral o placebo. El punto final primario, INR Anticoagulation therapy with warfarin, a common clinical practice, needs to be monitored using protombine time expressed as the International Normalized Ratio (INR; when safety range is exceeded, Vitamin K (Vit-K could be administered with preference orally. In Venezuela the specific oral preparation for Vit-K is not available. This is a double blinded, randomized, placebo controlled, clinical trial; 20 patients, age 18-60 year with initial INR ≥ 6, ≤10, were randomized to oral Vit-K 1.25mg (prepared from intravenous presentation or placebo plus withholding warfarin. INR < 3.5 at 24 hours of treatment (the primary end point was achieved by 70% among Vit-K, and 20% among placebo patients; given an absolute risk reduction (ARR, of 50% (CI95%: 14.4-85.6 ρ = 0.028, NNT 2 (CI95%: 1.3 - 6.9. No adverse events were recorded including INR < 2 at 24 hours of treatment administration. Our results are consistent with studies where specific oral presentation of Vit-K was used. The results indicate that oral administration of Vit-K, prepared from an intravenous Vit-K preparation, is safe and more effective to revert excessive anticoagulation than simply withholding warfarin, in places where specific preparation of oral Vit-K is not available or too expensive.

  20. Lesão pulmonar aguda induzida pela administração endovenosa de extrato da fumaça do cigarro Acute lung injury induced by the intravenous administration of cigarette smoke extract

    Directory of Open Access Journals (Sweden)

    Luciana Gomes Menezes

    2013-02-01

    Full Text Available OBJETIVO: Investigar os efeitos agudos da administração endovenosa de extrato da fumaça do cigarro (EFC em parâmetros funcionais respiratórios, inflamatórios e histológicos em ratos e comparar esse potencial modelo de lesão pulmonar aguda (LPA com aquele com o uso de ácido oleico (AO. MÉTODOS: Foram estudados 72 ratos Wistar machos divididos em quatro grupos: tratados somente com soro fisiológico (SF; grupo controle; tratados com EFC e SF (grupo EFC; tratados com SF e AO (grupo AO; e tratados com EFC e AO (grupo EFC/AO. RESULTADOS: As médias de complacência foram significantemente menores nos grupos AO e EFC/AO (2,12 ± 1,13 mL/cmH2O e 1,82 ± 0,77 mL/cmH2O, respectivamente do que no controle (3,67 ± 1,38 mL/cmH2O. A proporção de neutrófilos e a atividade das metaloproteinases 2 e 9 em lavado broncoalveolar foram significantemente maiores nos grupos AO e EFC/AO que no controle. O acometimento pulmonar avaliado por morfometria foi significantemente maior nos grupos AO e EFC/AO (72,9 ± 13,8% e 77,6 ± 18,0%, respectivamente do que nos grupos controle e EFC (8,7 ± 4,1% e 32,7 ± 13,1%, respectivamente, e esse acometimento foi significantemente maior no grupo EFC que no grupo controle. CONCLUSÕES: A administração endovenosa de EFC, nas doses e tempos deste estudo, associou-se à LPA mínima. O EFC não potencializou a LPA induzida por AO. Estudos adicionais são necessários para esclarecer o papel potencial desse modelo como método de estudo dos mecanismos de agressão pulmonar pelo tabaco.OBJECTIVE: To investigate the acute effects of intravenous administration of cigarette smoke extract (CSE on histological, inflammatory, and respiratory function parameters in rats, as well as to compare this potential acute lung injury (ALI model with that with the use of oleic acid (OA. METHODS: We studied 72 Wistar rats, divided into four groups: control (those injected intravenously with saline; CSE (those injected intravenously with

  1. Two different methods for repeated intrathecal administration in rats%大鼠鞘内反复给药两种方法的比较

    Institute of Scientific and Technical Information of China (English)

    任占杰; 于志军; 张增臻; 张成明; 张广学

    2009-01-01

    Objective To compare the feasibility of direct spinal puncture and reserving micro-catheter in spinal space during repeated intrathecal administration. Methods Forty Sprague-Dawley rats were randomly divided into 2 groups:direct spinal puncture (group puncture) and reserving micro-catheter in spinal space group (group reserve). The duration of operation were recorded. 5 days after operation, rata in both groups were intrathecally administerde morphine(10 μg/10μl) for 7 days and thermal withdrawal latency(TWL) were assessed. Results The operation in group reserve took shorter time than the group puncture, but micro-catheter were pulled out in 5 rats in group reserve. There is no difference of TWL between two groups. Conclusion Both methods are suitable for repeated intrathecal administration.%目的 比较大鼠蛛网膜下腔长期置管和反复蛛网膜下腔穿刺两种给药方法的难易程度及反复给药的可行性.方法 40只清洁级SD大鼠以随机数字表法分为置管组和穿刺组各20只.置管组通过蛛网膜下腔长期置管给药,穿刺组反复行蛛网膜下腔穿刺给药.记录每次进行操作所用的时间.2组均从实验第5天开始鞘内注射吗啡10 μg/1μl,连续给药7 d,用热辐射法测定大鼠热缩足潜伏期(TWL).对2组实验时间和TWL进行比较分析.结果 置管组操作时间较穿刺组短,差异有统计学意义(P<0.01).置管组5只大鼠导管脱出.鞘内给药后,置管组和穿刺组TWL测定值均较基础值增加,差异有统计学意义(P<0.01).2组间TWL测定值差异无统计学意义.结论 蛛网膜下腔长期置管和反复蛛网膜下腔穿刺均可作为鞘内多次给药方法,但在选择时应该考虑到操作难易程度、给药方式、反复给药并发症等因素的影响.

  2. Intravenous drug delivery in neonates: lessons learnt.

    Science.gov (United States)

    Sherwin, Catherine M T; Medlicott, Natalie J; Reith, David M; Broadbent, Roland S

    2014-06-01

    Intravenous drug administration presents a series of challenges that relate to the pathophysiology of the neonate and intravenous infusion systems in neonates. These challenges arise from slow intravenous flow rates, small drug volume, dead space volume and limitations on the flush volume in neonates. While there is a reasonable understanding of newborn pharmacokinetics, an appreciation of the substantial delay and variability in the rate of drug delivery from the intravenous line is often lacking. This can lead to difficulties in accurately determining the pharmacokinetic and pharmacodynamic relationship of drugs in the smallest patients. The physical variables that affect the passage of drugs through neonatal lines need to be further explored in order to improve our understanding of their impact on the delivery of drugs by this route in neonates. Through careful investigation, the underlying causes of delayed drug delivery may be identified and administration protocols can then be modified to ensure predictable, appropriate drug input kinetics.

  3. Intracoronary Versus Intravenous Administration of Abciximab in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention With Thrombus Aspiration The Comparison of Intracoronary Versus Intravenous Abciximab Administration During Emergency Reperfusion of ST-Segment Elevation Myocardial Infarction (CICERO) Trial

    NARCIS (Netherlands)

    Gu, Youlan L.; Kampinga, Marthe A.; Wieringa, Wouter G.; Fokkema, Marieke L.; Nijsten, Maarten W.; Hillege, Hans L.; van den Heuvel, Ad F. M.; Tan, Eng-Shiong; Pundziute, Gabija; van der Werf, Rik; Guyomi, Siyrous Hoseyni; van der Horst, Iwan C. C.; Zijlstra, Felix; de Smet, Bart J. G. L.

    2010-01-01

    Background-Administration of the glycoprotein IIb/IIIa inhibitor abciximab is an effective adjunctive treatment strategy during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Although small-scale studies have suggested beneficial effects of intracoronary

  4. The use of intravenous magnesium in non-preeclamptic pregnant women: fetal/neonatal neuroprotection.

    Science.gov (United States)

    Jacquemyn, Y; Zecic, A; Van Laere, D; Roelens, K

    2015-05-01

    To review the effect of intravenous magnesium in obstetrics on fetal/neonatal neuroprotection. A systematic review of published studies. Five randomized trials and 4 meta-analyses have shown a significant 32% reduction of cerebral palsy when administering magnesium sulfate in case of preterm delivery. The pathophysiologic mechanism is not fully unraveled: modulation of the inflammatory process, both in the mother and the fetus, and downregulation of neuronal stimulation seem to be involved. After long-term high-dose intravenous administration of magnesium, maternal and neonatal adverse effects such as maternal and neonatal hypotonia and osteoporosis and specific fetal/neonatal cerebral lesions have been described. In case of administration for less than 48 h at 1 g/h and a loading dose of 4 g, these toxic amounts are not achieved. American, Canadian and Australian guidelines recommend the use of intravenous magnesium in any threatening delivery at less than 32 weeks. The "number needed to treat" to avoid 1 cerebral palsy is between 15 and 35. Intravenous magnesium significantly reduces the risk for cerebral palsy in preterm birth. Open questions remain the optimal dosing schedule, whether or not repeating when delivery has been successfully postponed and a new episode of preterm labor occurs. Some concern has been raised on a too optimistic value for random error which might have led to over-optimistic conclusions in classic meta-analysis. Randomized trials comparing different doses and individual patient data meta-analysis might resolve these issues.

  5. Intravenous administration of the selective toll-like receptor 7 agonist DSR-29133 leads to anti-tumor efficacy in murine solid tumor models which can be potentiated by combination with fractionated radiotherapy

    Science.gov (United States)

    Dovedi, Simon J.; Adlard, Amy L.; Ota, Yosuke; Murata, Masashi; Sugaru, Eiji; Koga-Yamakawa, Erina; Eguchi, Ken; Hirose, Yuko; Yamamoto, Setsuko; Umehara, Hiroki; Honeychurch, Jamie; Cheadle, Eleanor J.; Hughes, Gareth; Jewsbury, Philip J.

    2016-01-01

    Strategies to augment anti-cancer immune responses have recently demonstrated therapeutic utility. To date clinical success has been achieved through targeting co-inhibitory checkpoints such as CTLA-4, PD-1, and PD-L1. However, approaches that target co-activatory pathways are also being actively being developed. Here we report that the novel TLR7-selective agonist DSR-29133 is well tolerated in mice and leads to acute immune activation. Administration of DSR-29133 leads to the induction of IFNα/γ, IP-10, TNFα, IL-1Ra and IL-12p70, and to a reduction in tumor burden in syngeneic models of renal cancer (Renca), metastatic osteosarcoma (LM8) and colorectal cancer (CT26). Moreover, we show that the efficacy of DSR-29133 was significantly improved when administered in combination with low-dose fractionated radiotherapy (RT). Effective combination therapy required weekly administration of DSR-29133 commencing on day 1 of a fractionated RT treatment cycle, whereas no enhancement of radiation response was observed when DSR-29133 was administered at the end of the fractionated RT cycle. Combined therapy resulted in curative responses in a high proportion of mice bearing established CT26 tumors which was dependent on the activity of CD8+ T-cells but independent of CD4+ T-cells and NK/NKT cells. Moreover, long-term surviving mice originally treated with DSR-29133 and RT were protected by a tumor-specific memory immune response which could prevent tumor growth upon rechallenge. These results demonstrate that DSR-29133 is a potent selective TLR7 agonist that when administered intravenously can induce anti-tumor immune responses that can be further enhanced through combination with low-dose fractionated RT. PMID:26959743

  6. Phlebitis caused by intravenous administration of alprostadil: analysis of 246 reports%静脉给予前列地尔致静脉炎:246份报告分析

    Institute of Scientific and Technical Information of China (English)

    高琲; 刘芳; 张俊

    2011-01-01

    with an infusion of alprostadil. Methods: Beijing Adverse Drug Reactions Monitoring Network database from 2003 to 2010 was searched for reports of phlebitis associated with an infusion of alprostadil. The patient's gender, age, family history and past history of phlebitis, primary disease, dosage form of alprostadil, route of administration, dosage, duration of treatment, time to phlebitis onset after drug administrations, clinical manifestations, severity of phlebitis, management and prognosis were analyzed. Results: A total of 246 reports with of phlebitis associated with alprostadil were collected. These patients comprised 167 men with average age (66. 7 ± 16. 1)years and 79 women with average age (68.1 ± 12. 3) years. Of the 246 patients, 23 patients had past history of phlebitis and 5 patients had family history of phlebitis. The main primary diseases were neurological disease(92 cases, 37. 4% ), surgical disease (26 cases, 10.6% ), and cardiovascular disease(25 cases, 10.2% ). Percentage of 99.2(244 cases) of patients received alprostadil injection and 0. 8% (2 cases) of patients received alprostadil powder for injection. The alprostadil injection dosage was 10 μg/d for 87.3% (213 cases) of patients and 20 μg/d for 8.6% (21 cases) of patients. The dosage of alprostadil power for injection was 10 μg/d for 0.8% (2 cases) of patients. The administration of drug was as follows: 97.2% (239 cases) of patients were treated with alprostadil by Ⅳ infusion and 2. 8% (7 cases) of patients were injected with alprostadil intravenously. The median of duration of treatment were 2 days. The median of time to phlebitis onset after drug administration was 20 minutes. When the severity of phlebitis was determined according to the criteria of Intravenous Nurses Society (INS), 145 patients (66.5% ) had grade 1, 57 patients (26.1% ) had grade 2, and 15 patients (6.9% ) had grade 3 phlebitis. The main clinical manifestations were erythema and pain in injection-site with

  7. Kounis syndrome secondary to intravenous cephalosporin administration

    Directory of Open Access Journals (Sweden)

    Sunkavalli Venkateswararao

    2015-01-01

    Full Text Available Kounis syndrome is a clinical condition due to hypersensitivity that culminates into acute coronary syndrome (ACS which can be fatal. A 36-year-old male with no conventional coronary risk factors presented elsewhere with a history of fever for 4 days, cough with expectoration, diarrhea and was treated with cephalosporin (Inj. Cefotaxime as an infusion along with analgesics. He experienced generalized itching 5 minutes after cefotaxime infusion followed by sweating, headache, chest pain with facial and periorbital swelling for which he was rushed to our hospital. On examination he was afebrile with a low blood pressure. Electrocardiogram taken at an outside hospital revealed incomplete right bundle branch block and ST depression V3–V5. Investigations showed increase in troponin T. He was managed with anti-histamines and standard protocol for treatment of ACS. Coronary angiogram revealed normal coronaries. The patient improved symptomatically with treatment and was discharged on an anti-platelet, nitrate and a statin.

  8. LC-UV Determination of Baicalin in Rabbit Plasma and Tissues for Application in Pharmacokinetics and Tissue Distribution Studies of Baicalin after Intravenous Administration of Liposomal and Injectable Formulations.

    Science.gov (United States)

    Wei, Yumeng; Pi, Chao; Yang, Gang; Xiong, Xiaoming; Lan, Yongshu; Yang, Hongru; Zhou, Yang; Ye, Yun; Zou, Yonggen; Zheng, Wenwu; Zhao, Ling

    2016-04-19

    A simple and sensitive LC-UV method to investigate the pharmacokinetics and biodistribution pattern of baicalin in rabbits was established and validated. Baicalin and the internal standard, rutin, were extracted from biosamples using acetonitrile as protein precipitation after pretreated with ammonium acetate buffer (pH 3.5; 1 M) to obtain a pure chromatographic peak and high extraction recovery. Chromatographic separation was achieved on a re