Flurbiprofen concentration in soft tissues is higher after topical application than after oral administration

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Kai, Shuken; Kondo, Eiji; Kawaguchi, Yasuyuki; Kitamura, Nobuto; Yasuda, Kazunori

2013-01-01

Aim To compare tissue concentrations of flurbiprofen resulting from topical application and oral administration according to the regulatory approved dosing guidelines. Method Sixteen patients were included in this study. Each patient was randomly assigned to the topical application or oral administration group. In each group, a pair of tapes or a tablet, containing a total of 40 mg flurbiprofen, was administered twice at 16 and 2 h before the surgery. Results The flurbiprofen concentration in the fat, tendon, muscle and periosteum tissues was significantly higher (P flurbiprofen to the human body, particularly to soft tissues near the body surface. PMID:22822928

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

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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

The effect of dose, dose rate, route of administration, and species on tissue and blood levels of benzene metabolites

International Nuclear Information System (INIS)

Henderson, R.F.; Sabourin, P.J.; Bechtold, W.E.; Griffith, W.C.; Medinsky, M.A.; Birnbaum, L.S.; Lucier, G.W.

1989-01-01

Studies were completed in F344/N rats and B6C3F 1 mice to determine the effect of dose, dose rate, route of administration, and rodent species on formation of total and individual benzene metabolites. Oral doses of 50 mg/kg or higher saturated the capacity for benzene metabolism in both rats and mice, resulting in an increased proportion of the administered dose being exhaled as benzene. The saturating air concentration for benzene metabolism during 6-hr exposures was between 130 and 900 ppm. At the highest exposure concentration, rats exhaled approximately half of the internal dose retained at the end of the 6-hr exposure as benzene; mice exhaled only 15% as benzene. Mice were able to convert more of the inhaled benzene to metabolites than were rats. In addition, mice metabolized more of the benzene by pathways leading to the putative toxic metabolites, benzoquinone and muconaldehyde, than did rats. In both rats and mice, the effect of increasing dose, administered orally or by inhalation, was to increase the proportion of the total metabolites that were the products of detoxification pathways relative to the products of pathways leading to putative toxic metabolites. This indicates low-affinity, high-capacity pathways for detoxification and high-affinity, low-capacity pathways leading to putative toxic metabolites. If the results of rodent studied performed at high doses were used to assess the health risk at low-dose exposures to benzene, the toxicity of benzene would be underestimated

Dose-dependent effects of oral tyrosine administration on plasma tyrosine levels and cognition in aging

NARCIS (Netherlands)

Rest, van de Ondine; Bloemendaal, Mirjam; Heus, De Rianne; Aarts, Esther

2017-01-01

The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults

Dose-Dependent Effects of Oral Tyrosine Administration on Plasma Tyrosine Levels and Cognition in Aging

NARCIS (Netherlands)

Rest, O. van de; Bloemendaal, M.; Heus, R.A.A. de; Aarts, E.

2017-01-01

The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults

Saliva oxytocin measures do not reflect peripheral plasma concentrations after intranasal oxytocin administration in men.

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Quintana, Daniel S; Westlye, Lars T; Smerud, Knut T; Mahmoud, Ramy A; Andreassen, Ole A; Djupesland, Per G

2018-05-16

Oxytocin plays an important role in social behavior. Thus, there has been significant research interest for the role of the oxytocin system in several psychiatric disorders, and the potential of intranasal oxytocin administration to treat social dysfunction. Measurement of oxytocin concentrations in saliva are sometimes used to approximate peripheral levels of oxytocin; however, the validity of this approach is unclear. In this study, saliva and plasma oxytocin was assessed after two doses of Exhalation Delivery System delivered intranasal oxytocin (8 IU and 24 IU), intravenous oxytocin (1 IU) and placebo in a double-dummy, within-subjects design with men. We found that intranasal oxytocin (8 IU and 24 IU) administration increased saliva oxytocin concentrations in comparison to saliva oxytocin concentration levels after intravenous and placebo administration. Additionally, we found that saliva oxytocin concentrations were not significantly associated with plasma oxytocin concentrations after either intranasal or intravenous oxytocin administration. Altogether, we suggest that saliva oxytocin concentrations do not accurately index peripheral oxytocin after intranasal or intravenous oxytocin administration, at least in men. The data indicates that elevated oxytocin saliva levels after nasal delivery primarily reflect exogenous administered oxytocin that is cleared from the nasal cavity to the oropharynx, and is therefore a weak surrogate for peripheral blood measurements. Copyright © 2018 Elsevier Inc. All rights reserved.

Therapeutic serum phenobarbital concentrations obtained using chronic transdermal administration of phenobarbital in healthy cats.

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Delamaide Gasper, Joy A; Barnes Heller, Heidi L; Robertson, Michelle; Trepanier, Lauren A

2015-04-01

Seizures are a common cause of neurologic disease, and phenobarbital (PB) is the most commonly used antiepileptic drug. Chronic oral dosing can be challenging for cat owners, leading to poor compliance. The purpose of this study was to determine if the transdermal administration of PB could achieve serum PB concentrations of between 15 and 45 μg/ml in healthy cats. Nineteen healthy cats were enrolled in three groups. Transdermal PB in pluronic lecithin organogel (PLO) was applied to the pinnae for 14 days at a dosage of 3 mg/kg q12h in group 1 (n = 6 cats) and 9 mg/kg q12h in group 2 (n = 7 cats). Transdermal PB in Lipoderm Activemax was similarly applied at 9 mg/kg q12h for 14 days in group 3 (n = 6 cats). Steady-state serum PB concentrations were measured at trough, and at 2, 4 and 6 h after the morning dose on day 15. In group 1, median concentrations ranged from 6.0-7.5 μg/ml throughout the day (observed range 0-11 μg/ml). Group 2 median concentrations were 26.0 μg/ml (observed range 18.0-37.0 μg/ml). For group 3, median concentrations ranged from 15.0-17.0 μg/ml throughout the day (range 5-29 μg/ml). Side effects were mild. One cat was withdrawn from group 2 owing to ataxia and sedation. These results show therapeutic serum PB concentrations can be achieved in cats following chronic transdermal administration of PB in PLO at a dosage of 9 mg/kg q12h. More individual variation was noted using Lipoderm Activemax. Transdermal administration may be an alternative for cats that are difficult to medicate orally. © ISFM and AAFP 2014.

Pharmacokinetics, Safety and Tolerability of Sacubitril/Valsartan (LCZ696) After Single-Dose Administration in Healthy Chinese Subjects.

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Han, Yi; Ayalasomayajula, Surya; Pan, Wei; Yang, Fan; Yuan, Yaozong; Langenickel, Thomas; Hinder, Markus; Kalluri, Sampath; Pal, Parasar; Sunkara, Gangadhar

2017-02-01

Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) and has been recently approved in several countries for the treatment of patients with heart failure and reduced ejection fraction. This was the first study conducted to characterise the pharmacokinetics of LCZ696 analytes (pro-drug sacubitril, active neprilysin inhibitor LBQ657 and valsartan) after single-dose administration of LCZ696 in healthy Chinese subjects. In this open-label, randomised, parallel-group study, following screening and baseline evaluation, eligible healthy subjects received single oral doses of LCZ696 50, 100, 200 or 400 mg. The pharmacokinetics, safety and tolerability of LCZ696 were assessed up to 72 h after dosing. A total of 40 healthy male subjects were enrolled, and all completed the study. Following oral administration, LCZ696 delivered systemic exposure to sacubitril, LBQ657 and valsartan with a median time to reach maximum plasma concentration (T max ) ranging from 0.50 to 1.25, 2.00 to 3.00 and 1.50 to 2.50 h, respectively, over the investigated dose range. The mean terminal elimination half-life (T 1/2 ) ranged from 0.89 to 1.35, 8.57 to 9.24 and 5.33 to 7.91 h for sacubitril, LBQ657 and valsartan, respectively. The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last ), and maximum plasma concentration (C max ) for LBQ657 increased dose proportionally over the entire dose range. Dose linear increase in the exposure was observed across the dose range for sacubitril and valsartan. LCZ696 was safe and well tolerated at all doses in this study. Adverse events of only mild intensity, which required no treatment, were reported in 6 (15 %) subjects. The pharmacokinetic profiles of LCZ696 analytes in Chinese subjects are similar to those reported previously in Caucasian subjects.

Transcriptional Response in Mouse Thyroid Tissue after 211At Administration: Effects of Absorbed Dose, Initial Dose-Rate and Time after Administration.

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Nils Rudqvist

Full Text Available 211At-labeled radiopharmaceuticals are potentially useful for tumor therapy. However, a limitation has been the preferential accumulation of released 211At in the thyroid gland, which is a critical organ for such therapy. The aim of this study was to determine the effect of absorbed dose, dose-rate, and time after 211At exposure on genome-wide transcriptional expression in mouse thyroid gland.BALB/c mice were i.v. injected with 1.7, 7.5 or 100 kBq 211At. Animals injected with 1.7 kBq were killed after 1, 6, or 168 h with mean thyroid absorbed doses of 0.023, 0.32, and 1.8 Gy, respectively. Animals injected with 7.5 and 100 kBq were killed after 6 and 1 h, respectively; mean thyroid absorbed dose was 1.4 Gy. Total RNA was extracted from pooled thyroids and the Illumina RNA microarray platform was used to determine mRNA levels. Differentially expressed transcripts and enriched GO terms were determined with adjusted p-value 1.5, and p-value <0.05, respectively.In total, 1232 differentially expressed transcripts were detected after 211At administration, demonstrating a profound effect on gene regulation. The number of regulated transcripts increased with higher initial dose-rate/absorbed dose at 1 or 6 h. However, the number of regulated transcripts decreased with mean absorbed dose/time after 1.7 kBq 211At administration. Furthermore, similar regulation profiles were seen for groups administered 1.7 kBq. Interestingly, few previously proposed radiation responsive genes were detected in the present study. Regulation of immunological processes were prevalent at 1, 6, and 168 h after 1.7 kBq administration (0.023, 0.32, 1.8 Gy.

Paracetamol (acetaminophen) protein adduct concentrations during therapeutic dosing.

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Heard, Kennon; Green, Jody L; Anderson, Victoria; Bucher-Bartelson, Becki; Dart, Richard C

2016-03-01

Paracetamol protein adducts (PPA) are a biomarker of paracetamol exposure. PPA are quantified as paracetamol-cysteine (APAP-CYS), and concentrations above 1.1 μmol l(-1) have been suggested as a marker of paracetamol-induced hepatotoxicity. However, there is little information on the range of concentrations observed during prolonged therapeutic dosing. The aim of the present study was to describe the concentration of PPA in the serum of subjects taking therapeutic doses of paracetamol for at least 16 days. Preplanned secondary aim of a prospective randomized controlled (placebo vs. 4g day(-1) paracetamol) trial. We measured subjects' serum PPA concentrations every 3 days for a minimum of 16 days. We also measured concentrations on study days 1-3 and 16-25 in subsets of patients. PPA were quantified as APAP-CYS after gel filtration and protein digestion using liquid chromatography/mass spectrometry. Ninety per cent of subjects had detectable PPA after five doses. Median APAP-CYS concentrations in paracetamol-treated subjects increased to a plateau of 0.1 μmol l(-1) on day 7, where they remained. The highest concentration measured was 1.1 μmol l(-1) and two subjects never had detectable PPA levels. PPA were detected in the serum of 78% of subjects 9 days after their final dose. PPA are detectable in the vast majority of subjects taking therapeutic doses of paracetamol. While most have concentrations well below the threshold associated with hepatotoxicity, concentrations may approach 1.1 μmol l(-1) in rare cases. Adducts are detectable after a few doses and can persist for over a week after dosing is stopped. © 2015 The British Pharmacological Society.

Pharmacokinetic interaction of enrofloxacin/trimethoprim combination following single-dose intraperitoneal and oral administration in rats.

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Choi, Myung-Jin; Yohannes, Sileshi Belew; Lee, Seung-Jin; Damte, Dereje; Kim, Jong-Choon; Suh, Joo-Won; Park, Seung-Chun

2014-03-01

The pharmacokinetic interaction of enrofloxacin and trimethoprim was evaluated after single-dose intraperitoneal or oral co-administration in rats. Plasma concentrations of the two drugs were determined by high-performance liquid chromatography. Following intraperitoneal combination, a significant (P trimethoprim, respectively. There was a significant (P trimethoprim. Further study is recommended in other species of animals.

Lack of dose dependent kinetics of methyl salicylate-2-O-β-D-lactoside in rhesus monkeys after oral administration.

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He, Yangyang; Yan, Yu; Zhang, Tiantai; Ma, Yinzhong; Zhang, Wen; Wu, Ping; Song, Junke; Wang, Shuang; Du, Guanhua

2015-04-22

Methyl salicylate-2-O-β-d-lactoside (MSL) is one of the main active components isolated from Gaultheria yunnanensis, which is a traditional Chinese medicine used to treat arthritis and various aches and pains. Pharmacological researches showed that MSL had various effective activities in both in vivo and in vitro experiments. However, the pharmacokinetics features and oral bioavailability of MSL in primates were not studied up to now. To study the pharmacokinetics of different doses of MSL in rhesus monkeys and investigate the absolute bioavailability of MSL after oral administration. Male and female rhesus monkeys were either orally administrated with MSL 200, 400 and 800 mg/kg or received an intravenous dose of 20mg/kg randomly. The levels of MSL and salicylic acid (SA) in plasma were simultaneous measured by a simple, sensitive and reproducible high performance liquid chromatography method. Mean peak plasma concentration values for groups treated with 200, 400 and 800 mg/kg doses ranged from 48.79 to 171.83 μg/mL after single-dose oral administration of MSL, and mean area under the concentration-time curve values ranged from 195.16 to 1107.76 μg/mL h. Poor linearity of the kinetics of SA after oral administration of MSL was observed in the regression analysis of the Cmax-dose plot (r(2)=0.812), CL-dose plot (r(2)=0.225) and AUC(0-t)-dose plot (r(2)=0.938). Absolute bioavailability of MSL was assessed to be 118.89 ± 57.50, 213.54 ± 58.98 and 168.72 ± 76.58%, respectively. Bioavailability of MSL after oral administration in rhesus monkeys was measured for the first time. Pharmacokinetics parameters did not appear to be dose proportional among the three oral doses of treatments, and MSL showed an apparent absolute bioavailability in excess of 100% in rhesus monkeys based on the present study. In addition, a rapid, sensitive and reliable HPLC method was established and demonstrated for the research of traditional Chinese medicine in this study. Copyright �

Serum thyroxine concentrations following fixed-dose radioactive iodine treatment in hyperthyroid cats: 62 cases (1986-1989)

International Nuclear Information System (INIS)

Meric, S.M.; Rubin, S.I.

1990-01-01

The medical records of 62 hyperthyroid cats treated with a fixed dose of 4 mCi of radioactive iodine (131I) were reviewed. In 60 cats, serum thyroxine concentrations were determined after treatment, allowing evaluation of treatment success. Eighty-four percent of the cats had normal serum thyroxine concentrations after treatment. Five of the 60 cats (8%) remained hyperthyroxinemic after treatment. Five cats (8%) were hypothyroxinemic when evaluated within 60 days of treatment. Three of these cats had normal serum thyroxine concentrations 6 months after treatment, and none had clinical signs of hypothyroidism. The administration of a fixed dose of 4 mCi of 131I was determined to be an effective treatment for feline hyperthyroidism

Salivary Oxytocin Concentrations in Males following Intranasal Administration of Oxytocin: A Double-Blind, Cross-Over Study.

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Daughters, Katie; Manstead, Antony S R; Hubble, Kelly; Rees, Aled; Thapar, Anita; van Goozen, Stephanie H M

2015-01-01

The use of intranasal oxytocin (OT) in research has become increasingly important over the past decade. Although researchers have acknowledged a need for further investigation of the physiological effects of intranasal administration, few studies have actually done so. In the present double-blind cross-over study we investigated the longevity of a single 24 IU dose of intranasal OT measured in saliva in 40 healthy adult males. Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes. Results showed significant individual differences in response to intranasal OT administration. To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations. The results are consistent with previous research in suggesting that salivary OT is a valid matrix for OT measurement. The results also suggest that the post-administration 'wait-time' prior to starting experimental tasks could be reduced to 30 minutes, from the 45 minutes typically used, thereby enabling testing during peak OT concentrations. Further research is needed to ascertain whether OT concentrations after intranasal administration follow similar patterns in females, and different age groups.

Salivary Oxytocin Concentrations in Males following Intranasal Administration of Oxytocin: A Double-Blind, Cross-Over Study.

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Katie Daughters

Full Text Available The use of intranasal oxytocin (OT in research has become increasingly important over the past decade. Although researchers have acknowledged a need for further investigation of the physiological effects of intranasal administration, few studies have actually done so. In the present double-blind cross-over study we investigated the longevity of a single 24 IU dose of intranasal OT measured in saliva in 40 healthy adult males. Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes. Results showed significant individual differences in response to intranasal OT administration. To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations. The results are consistent with previous research in suggesting that salivary OT is a valid matrix for OT measurement. The results also suggest that the post-administration 'wait-time' prior to starting experimental tasks could be reduced to 30 minutes, from the 45 minutes typically used, thereby enabling testing during peak OT concentrations. Further research is needed to ascertain whether OT concentrations after intranasal administration follow similar patterns in females, and different age groups.

Pharmacokinetics of buprenorphine after single-dose subcutaneous administration in red-eared sliders (Trachemys scripta elegans).

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Kummrow, Maya S; Tseng, Florina; Hesse, Leah; Court, Michael

2008-12-01

Buprenorphine, a mu opioid receptor agonist, is expected to be a suitable analgesic drug for use in reptiles. However, to date, dosage recommendations have been based on anecdotal observations. The aim of this study was to provide baseline pharmacokinetic data in red-eared sliders (Trachemys scripta elegans) targeting a plasma level of 1 ng/ml reported effective for analgesia in humans. Serial blood samples were taken after subcutaneous injection of buprenorphine, and plasma buprenorphine levels were measured by radioimmunoassay. Pharmacokinetic parameters of a lower dose (0.02 mg/kg) injected into the forelimb were compared with a higher dose (0.05 mg/kg) given in the same forelimb as well as a lower dose (0.02 mg/kg) given in the hind limb of the same animals with 2 wk between studies. After administration of 0.05 mg/kg in the front limb, 85% of animals maintained the minimum effective plasma level for 24 hr, while only 43% of animals maintained this level after 0.02 mg/kg. After hind limb injection at 0.02 mg/kg, maximum plasma concentrations and areas under the buprenorphine concentration-time curve were less than 20% and 70%, respectively, of values after forelimb injection, consistent with substantial first pass extraction by the liver. Furthermore, a secondary rise in the buprenorphine level was found after having only a hind limb injection, probably from enterohepatic recirculation of glucuronidated drug. In conclusion, buprenorphine dosages of at least 0.075 mg/kg s.i.d. should be appropriate for evaluation of analgesia efficacy, and front limb administration may be preferable to hind limb administration for optimal drug exposure.

Radiotherapy combined with daily administration of low dose cisplatin for head and neck cancer

International Nuclear Information System (INIS)

Fujita, Masahiro; Murayama, Shigeyuki; Matayoshi, Yoshinobu; Ikeda, Hiroshi; Shimizutani, Kimishige; Inoue, Toshihiko; Kozuka, Takahiro; Masaki, Norie.

1990-01-01

Serum concentrations of cisplatin (CDDP) and acute complications were studied in patients treated for head and neck cancer by radiotherapy combined with daily administration of low doses of CDDP (5 mg/m 2 or 6 mg/body) at Osaka University Hospital between March 1988 and December 1989. Serum concentrations of total-CDDP (6 patients) and free-CDDP (2 patients) were studied in cases injected intravenously with 5 mg/m 2 daily. Total-CDDP determined just before daily administration of CDDP was increased gradually (0.35 to 0.64 μg/ml by the 7th day, 0.42 to 0.91 μg/ml by the 14th day and 0.60 to 0.82 μg/ml by the 20th or 21st day) and still observed in the serum for more than two weeks after cessation of the chemotherapy. Serum concentrations of free-CDDP were about 0.35 μg/ml at 5 minutes and 0.15 μg/ml at 30 minutes after the intravenous injection of CDDP. Incidence of the acute complications more severe than grade 2 were nausea and vomiting: 4/52 (8%), leukopenia: 11/52 (21%) and thrombocytopenia: 4/52 (8%). Incidence of myelosuppression (leukopenia and/or thrombocytopenia) was 11/26(42%) when the total dose of CDDP exceeded 120 mg, and 3/26 (12%) when it was less than 120 mg. Transient renal dysfunction (increase of serum creatinine) of grade 1 was seen in only 3 patients. (author)

Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats

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Pawluski, Jodi L.; van Donkelaar, Eva; Abrams, Zipporah; Steinbusch, Harry W. M.; Charlier, Thierry D.

2014-01-01

Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1) cookie and (2) osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL) at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat. PMID:24757568

Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats

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Jodi L. Pawluski

2014-01-01

Full Text Available Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1 cookie and (2 osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat.

The effect of single low-dose dexamethasone on blood glucose concentrations in the perioperative period: a randomized, placebo-controlled investigation in gynecologic surgical patients.

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Murphy, Glenn S; Szokol, Joseph W; Avram, Michael J; Greenberg, Steven B; Shear, Torin; Vender, Jeffery S; Gray, Jayla; Landry, Elizabeth

2014-06-01

The effect of single low-dose dexamethasone therapy on perioperative blood glucose concentrations has not been well characterized. In this investigation, we examined the effect of 2 commonly used doses of dexamethasone (4 and 8 mg at induction of anesthesia) on blood glucose concentrations during the first 24 hours after administration. Two hundred women patients were randomized to 1 of 6 groups: Early-control (saline); Early-4 mg (4 mg dexamethasone); Early-8 mg (8 mg dexamethasone); Late-control (saline); Late-4 mg (4 mg dexamethasone); and Late-8 mg (8 mg dexamethasone). Blood glucose concentrations were measured at baseline and 1, 2, 3, and 4 hours after administration in the early groups and at baseline and 8 and 24 hours after administration in the late groups. The incidence of hyperglycemic events (the number of patients with at least 1 blood glucose concentration >180 mg/dL) was determined. Blood glucose concentrations increased significantly over time in all control and dexamethasone groups (from median baselines of 94 to 102 mg/dL to maximum medians ranging from 141 to 161.5 mg/dL, all P < 0.001). Blood glucose concentrations did not differ significantly between the groups receiving dexamethasone (either 4 or 8 mg) and those receiving saline at any measurement time. The incidence of hyperglycemic events did not differ in any of the early (21%-28%, P = 0.807) or late (13%-24%, P = 0.552) groups. Because blood glucose concentrations during the first 24 hours after administration of single low-dose dexamethasone did not differ from those observed after saline administrations, these results suggest clinicians need not avoid using dexamethasone for nausea and vomiting prophylaxis out of concerns related to hyperglycemia.

Time-Dependent Decline in Serum Phenytoin Concentration with Heightened Convulsive Seizure Risk by Prolonged Administration of Fosphenytoin in Japanese: A Retrospective Study.

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Ohno, Yuta; Niwa, Takashi; Hirai, Keita; Suzuki, Keiko; Yamada, Yuto; Hayashi, Yuichi; Hayashi, Hideki; Suzuki, Akio; Itoh, Yoshinori

2018-04-20

Because clinical data to confirm the safety and effectiveness of fosphenytoin, a prodrug of phenytoin, are insufficient, the length of administration of fosphenytoin is restricted. Nevertheless, some cases require fosphenytoin administration for more than a few days. The aim of this study was to retrospectively investigate the serum concentration of phenytoin in adult Japanese patients who received intravenous fosphenytoin therapy for more than 3 days. Patients injected with intravenous fosphenytoin for more than 3 days at Gifu University Hospital between January 2012 and September 2014 were enrolled. Individual pharmacokinetic parameters were predicted by Bayesian estimation using NONMEM software, and the maintenance dose of fosphenytoin required to maintain the therapeutic trough concentration (10-20 μg/mL) was calculated from the parameters. Among a total of 8 patients, the serum trough concentration of phenytoin decreased with each day after repeated injection of fosphenytoin. The incidence rate of significant convulsive seizures was increased time-dependently (0% on day 1, 12.5% on day 2, 25% on day 3, and 66.7% on day 4 and after). Phenytoin clearance showed a time-dependent increase. The maintenance dose of fosphenytoin required to maintain the therapeutic trough concentration was simulated to be 779.8 ± 316.8 mg/day, a dose that was markedly higher than the actual maintenance dose (414.1 ± 55.7 mg/day). Prolonged use of fosphenytoin for such patients as those with autoimmune-mediated encephalopathy accompanied with reflux disease and/or ileus time-dependently decreased the serum concentration of phenytoin and increased the risk of convulsion. Therefore, the maintenance dose should be increased to maintain the therapeutic serum concentration.

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

1997 N-Basin Administrative Control Level Dose Extension

International Nuclear Information System (INIS)

Nellesen, A.L.

1997-04-01

This document provides justification for extending the Administrative Control Level of 500 mrem per year to 1,000 mrem per year Total Effective Dose Equivalent for workers involved with N-Reactor Basin Deactivation in accordance with established procedures

Maternal Buprenorphine Dose, Placenta Buprenorphine and Metabolite Concentrations and Neonatal Outcomes

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Concheiro, Marta; Jones, Hendreé E.; Johnson, Rolley E.; Choo, Robin; Shakleya, Diaa M.; Huestis, Marilyn A.

2010-01-01

Buprenorphine is approved as pharmacotherapy for opioid dependence in non-pregnant patients in multiple countries, and is currently under investigation for pregnant women in the US and Europe. This research evaluates the disposition of buprenorphine, opiates, cocaine, and metabolites in 5 term placentas from a US cohort. Placenta and matched meconium concentrations were compared, and relationships between maternal buprenorphine dose, placenta concentrations, and neonatal outcomes following controlled administration during gestation were investigated. Buprenorphine and/or metabolites were detected in all placenta specimens and were uniformly distributed across this tissue (CV<27.5%, 4 locations), except for buprenorphine in 3 placentas. In 2 of these, buprenorphine was not detected in some locations and, in the 3rd placenta, was totally absent. Median (range) concentrations were buprenorphine 1.6ng/g (not detected to 3.2), norbuprenorphine 14.9ng/g (6.2 to 24.2), buprenorphine-glucuronide 3ng/g (1.3 to 5.0) and norbuprenorphine-glucuronide 14.7ng/g (11.4 to 25.8). Placenta is a potential alternative matrix for detecting in utero buprenorphine exposure, but at lower concentrations (15–70 fold) than in meconium. Statistically significant correlations were observed for mean maternal daily dose from enrollment to delivery and placenta buprenorphine-glucuronide concentration, and for norbuprenorphine-glucuronide concentrations and time to neonatal abstinence syndrome (NAS) onset and duration, and for norbuprenorphine/norbuprenorphine-glucuronide ratio and maximum NAS score, and newborn length. Analysis of buprenorphine and metabolites in this alternative matrix, an abundant waste product available at the time of delivery, may be valuable for prediction of neonatal outcomes for clinicians treating newborns of buprenorphine-exposed women. PMID:20216119

Inactive Doses and Protein Concentration of Gamma Irradiated Yersinia Enterocolitica

International Nuclear Information System (INIS)

Irawan Sugoro; Sandra Hermanto

2009-01-01

Yersinia enterocolitica is one of bacteria which cause coliform mastitis in dairy cows. The bacteria could be inactivated by gamma irradiation as inactivated vaccine candidate. The experiment has been conducted to determine the inactive doses and the protein concentration of Yersinia enterocolitica Y3 which has been irradiated by gamma rays. The cells cultures were irradiated by gamma rays with doses of 0, 100, 200, 400, 600, 800, 1.000 and 1.500 Gy (doses rate was 1089,59 Gy/hours). The inactive dose was determined by the drop test method and the protein concentration of cells were determined by Lowry method. The results showed that the inactive doses occurred on 800 – 1500 Gy. The different irradiation doses of cell cultures showed the effect of gamma irradiation on the protein concentration that was random and has a significant effect on the protein concentration. (author)

Intravenous administration of high-dose Paclitaxel reduces gut-associated lymphoid tissue cell number and respiratory immunoglobulin A concentrations in mice.

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Moriya, Tomoyuki; Fukatsu, Kazuhiko; Noguchi, Midori; Okamoto, Koichi; Murakoshi, Satoshi; Saitoh, Daizoh; Miyazaki, Masaru; Hase, Kazuo; Yamamoto, Junji

2014-02-01

Chemotherapy remains a mainstay of treatment for cancer patients. However, anti-cancer drugs frequently cause a wide range of side effects, including leukopenia and gastrointestinal toxicity. These adverse effects can lead to treatment delays or necessitate temporary dose reductions. Although chemotherapy-related changes in gut morphology have been demonstrated, the influences of chemotherapeutic regimens on gut immunity are understood poorly. This study aimed to examine whether the anti-cancer drug paclitaxel (PTX) impairs gut immunity in mice. Male ICR mice were randomized into three groups: Control, low-dose PTX (low PTX; 2 mg/kg), or high-dose PTX (high PTX; 4 mg/kg). A single intravenous dose was given. On day seven after the injection, lymphocytes from Peyer patches (PP), intraepithelial (IE) spaces, and the lamina propria (LP) were counted and analyzed by flow cytometry (CD4(+), CD8(+), αβTCR(+), γδTCR(+), B220(+)). Immunoglobulin A (IgA) concentrations were measured in small intestinal and respiratory tract washings. Total, CD4(+) and γδTCR(+) lymphocyte numbers in PPs were significantly lower in the high PTX than in the control group. The CD4(+) lymphocyte numbers in the IE spaces were significantly lower in both PTX groups than in the control group. Respiratory tract IgA concentrations were lower in the high PTX than in the control group. The present data suggest high-dose PTX impairs mucosal immunity, possibly rendering patients more vulnerable to infection. Careful dose selection and new therapies may be important for maintaining mucosal immunity during PTX chemotherapy.

Maternal Methadone Dose, Placental Methadone Concentrations, and Neonatal Outcomes

Science.gov (United States)

de Castro, Ana; Jones, Hendreé E.; Johnson, Rolley E.; Gray, Teresa R.; Shakleya, Diaa M.; Huestis, Marilyn A.

2015-01-01

BACKGROUND Few investigations have used placenta as an alternative matrix to detect in utero drug exposure, despite its availability at the time of birth and the large amount of sample. Methadone-maintained opioid-dependent pregnant women provide a unique opportunity to examine the placental disposition of methadone and metabolite [2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)], to explore their correlations with maternal methadone dose and neonatal outcomes, and to test the ability to detect in utero exposure to illicit drugs. METHODS We calculated the correlations of placental methadone and EDDP concentrations and their correlations with maternal methadone doses and neonatal outcomes. Cocaine- and opiate-positive placenta results were compared with the results for meconium samples and for urine samples collected throughout gestation. RESULTS Positive correlations were found between placental methadone and EDDP concentrations (r = 0.685), and between methadone concentration and methadone dose at delivery (r = 0.542), mean daily dose (r = 0.554), mean third-trimester dose (r = 0.591), and cumulative daily dose (r = 0.639). The EDDP/methadone concentration ratio was negatively correlated with cumulative daily dose (r = 0.541) and positively correlated with peak neonatal abstinence syndrome (NAS) score (r = 0.513). Placental EDDP concentration was negatively correlated with newborn head circumference (r = 0.579). Cocaine and opiate use was detected in far fewer placenta samples than in thrice-weekly urine and meconium samples, a result suggesting a short detection window for placenta. CONCLUSIONS Quantitative methadone and EDDP measurement may predict NAS severity. The placenta reflects in utero drug exposure for a shorter time than meconium but may be useful when meconium is unavailable or if documentation of recent exposure is needed. PMID:21245372

Effect of low dose ionizing radiation upon concentration of

International Nuclear Information System (INIS)

Viliae, M.; Kraljeviae, P.; Simpraga, M.; Miljaniae, S.

2004-01-01

It is known that low dose ionizing radiation might have stimulating effects (Luckey, 1982, Kraljeviae, 1988). This fact has also been confirmed in the previous papers of Kraljeviae et al. (2000-2000a; 2001). Namely, those authors showed that irradiation of chicken eggs before incubation by a low dose of 0.15 Gy gamma radiation increases the activity aspartateaminotrasferases (AST) and alanine-aminotransferases (ALT) in blood plasma of chickens hatched from irradiated eggs, as well as growth of chickens during the fattening period. Low doses might also cause changes in the concentration of some biochemical parameters in blood plasma of the same chickens such as changes in the concentration of total proteins, glucose and cholesterol. In this paper, an attempt was made to investigate the effects of low dose gamma radiation upon the concentration of sodium and potassium in the blood plasma of chickens which were hatched from eggs irradiated on the 19th day of incubation by dose of 0.15 Gy. Obtained results were compared with the results from the control group (chickens hatched from nonirradiated eggs). After hatching, all other conditions were the same for both groups. Blood samples were drawn from heart, and later from the wing vein on days 1, 3, 5, 7, 10, 20, 30 and 42. The concentration of sodium and potassium was determined spectrophotometrically by atomic absorbing spectrophotometer Perkin-Elmer 1100B. The concentration of sodium and potassium in blood plasma of chickens hatched from eggs irradiated on the 19th day of incubation by dose of 0.15 Gy indicated a statistically significant increase (P>0.01) only on the first day of the experiment. Obtained results showed that irradiation of eggs on the 19th day of incubation by dose of 0.15 Gy gamma radiation could have effects upon the metabolism of electrolytes in chickens. (Author)

Intravenous infusion of docosahexaenoic acid increases serum concentrations in a dose-dependent manner and increases seizure latency in the maximal PTZ model.

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Trépanier, Marc-Olivier; Kwong, Kei-Man; Domenichiello, Anthony F; Chen, Chuck T; Bazinet, Richard P; Burnham, W M

2015-09-01

Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) that has been shown to raise seizure thresholds in the maximal pentylenetetrazole model following acute subcutaneous (s.c.) administration in rats. Following s.c. administration, however, the dose-response relationship for DHA has shown an inverted U-pattern. The purposes of the present experiment were as follows: (1) to determine the pattern of serum unesterified concentrations resulting from the intravenous (i.v.) infusions of various doses of DHA, (2) to determine the time course of these concentrations following the discontinuation of the infusions, and (3) to determine whether seizure protection in the maximal PTZ model would correlate with serum unesterified DHA levels. Animals received 5-minute i.v. infusions of saline or 25, 50, 100, or 200mg/kg of DHA via a cannula inserted into one of the tail veins. Blood was collected during and after the infusions by means of a second cannula inserted into the other tail vein (Experiment 1). A separate group of animals received saline or 12.5-, 25-, 50-, 100-, or 200 mg/kg DHA i.v. via a cannula inserted into one of the tail veins and were then seizure-tested in the maximal PTZ model either during infusion or after the discontinuation of the infusions. Slow infusions of DHA increased serum unesterified DHA concentrations in a dose-dependent manner, with the 200-mg/kg dose increasing the concentration approximately 260-fold compared with saline-infused animals. Following discontinuation of the infusions, serum concentrations rapidly dropped toward baseline, with half-lives of approximately 40 and 11s for the 25-mg/kg dose and 100-mg/kg dose, respectively. In the seizure-tested animals, DHA significantly increased latency to seizure onset in a dose-dependent manner. Following the discontinuation of infusion, seizure latency rapidly decreased toward baseline. Overall, our study suggests that i.v. infusion of unesterified DHA results in

The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.

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Schlienz, Nicolas J; Lee, Dustin C; Stitzer, Maxine L; Vandrey, Ryan

2018-06-01

There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. Non-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180-240 mg/day; 60-80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. Participants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Amphetamine concentrations in human urine following single-dose administration of the calcium antagonist prenylamine-studies using fluorescence polarization immunoassay (FPIA) and GC-MS.

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Kraemer, Thomas; Roditis, Susanne K; Peters, Frank T; Maurer, Hans H

2003-03-01

Prenylamine (R,S-N-(3,3-diphenylpropyl-methyl-2-phenethylamine), a World Health Organization class V calcium antagonist, is known to be metabolized to amphetamine. In this study, amphetamine concentrations after a single-dose administration of prenylamine were determined to check if they reached values that could be of analytical and/or pharmacological importance in clinical and forensic toxicology. Enantiomeric composition of amphetamine was also studied. Five volunteers received a single 120-mg oral dose of prenylamine. Urine samples were analyzed using the Abbott TDx immunoassay Amphetamine/Methamphetamine II and using our routine systematic toxicological analysis (STA) gas chromatography-mass spectrometry (GC-MS) procedure. For quantitation purposes, GC-MS was used in the selected-ion monitoring (SIM) mode (ions m/z 118, 122, 240, 244) after solid-phase extraction (Isolute Confirm HCX) and derivatization (heptafluorobutyric anhydride). Amphetamine-d5 was used as internal standard (IS). Chiral separation of the heptafluorobutyrated amphetamine enantiomers was achieved using an Astec Chiraldex G-PN column. The TDx results showed a great variability for the different volunteers. A urine sample of one volunteer showed results as high as 3200 ng/mL, whereas the urine samples of another volunteer never gave results greater than the TDx detection limit (100 ng/mL). Using the STA procedure, the presence of amphetamine could be confirmed in all urine samples with TDx results greater than the cutoff value (300 ng/mL). Using the GC-MS SIM method, amphetamine concentrations up to 1280 ng/mL were determined. Chiral analysis revealed that both enantiomers of amphetamine were present in the samples with a surplus of the S(+)-enantiomer in the early phase of excretion. Forensic implications are discussed.

Biokinetic study of 131I following ablation dose administration

International Nuclear Information System (INIS)

Nascimento, A.C.H.; Lipsztein, J.L.; Lucena, E.A.; Dantas, B.M.; Rebelo, A.M.O.; Mello, R.C.

2002-01-01

Aim: The aim of this investigation is to study biokinetics from internally 131 I deposited for thyroid cancer patients during radioiodine therapy (2 to 3 days), after ablation dose administration (3.7 GBq). These data will help in the elaboration of a metabolic model, which will permit absorbed dose assessment for this specific case, since the biokinetic models for iodine available in scientific literature can not be applied to thyroidectomized patient's studies. Material and Methods: Four females patients, between 22 and 50 years old, without metastases, between 1.9 to 6% of remnant thyroid tissue uptake, agreed to contribute to this study. For the in vivo bioassay, periodical measurements were performed along internment time (2 to 3 days), just after Na 131 I dose administration (3.7 GBq). For this, we used the counting system for Nuclear Medicine model 13S002, IEN/CNEN- Brazil, which was adapted with lead filters, in order to allow the work with high rate counting. The measurements were performed in two geometries: thyroid region and thigh. Results: For each patient, we have done approximately 26 measurements for both geometries, starting at the first hour following dose administration until the release from hospital of patient. The results of counting rate (cps) were plotted against time (h). The measurements suggest a relation between remnant thyroid tissue uptake values and the time where counting rates start decreasing. In addition, it was observed a correlation between remnant thyroid tissue radioactive burdens and the circulating iodine through time. Conclusion: It is necessary to follow-up a greater number of patients aiming to confirm the observed correlations and with a greater number of measurements during the first 24 hours, in other to delimit the time range of increasing and decreasing counting rate

High thiamine diphosphate concentrations in erythrocytes can be achieved in dialysis patients by oral administration of benfontiamine.

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Frank, T; Bitsch, R; Maiwald, J; Stein, G

2000-06-01

The influence of either orally administered S-benzoylthiamine-O-monophosphate (benfotiamine) or thiamine nitrate on the thiamine status was tested in a randomised, two-group comparison study in 20 end-stage renal disease (ESRD) patients. Main outcome measures were the pharmacokinetics of thiamine diphosphate (TDP) in blood, the in vitro erythrocyte transketolase activity, its activation coefficient (alpha-ETK) and the TDP concentration in erythrocytes. After ingestion of a single dose of either 100 mg thiamine nitrate (corresponding to 305 micromol thiamine) or 100 mg benfotiamine (corresponding to 214 micromol thiamine), the blood levels of thiamine phosphate esters were analysed by means of high-performance liquid chromatography for a 24-h period. The TDP concentration in erythrocytes was calculated using the haematocrit and TDP concentration in blood. Erythrocyte transketolase activity and alpha-ETK were measured before and 10 h after administration. The pharmacokinetics of TDP in blood were compared with healthy subjects of other studies retrieved from database query. Regarding the blood concentrations of TDP, the patients with ESRD had a 4.3 times higher area under the concentration time curve after benfotiamine administration than after thiamine nitrate. After benfotiamine administration, the peak plasma concentration of TDP exceeded that in healthy subjects by 51%. In the ESRD patients, after 24 h, the mean TDP concentration in erythrocytes increased from 158.7+/-30.9 ng/ml initially to 325.8+/-50.9 ng/ml after administration of benfotiamine and from 166.2+/-51.9 ng/ml to 200.5+/-50.0 ng/ml after thiamine nitrate administration. The ratio between the maximum erythrocyte TDP concentration and basal concentration was 2.66+/-0.6 in the benfotiamine group and 1.44+/-0.2 in the group receiving thiamine nitrate (P benfotiamine intake (P = 0.02) and from 3.71+/-0.8 microkat/l to 4.02+/-0.7 microkat/l after thiamine nitrate intake (P = 0.08). Likewise, alpha

GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects.

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Spreen, William; Ford, Susan L; Chen, Shuguang; Wilfret, David; Margolis, David; Gould, Elizabeth; Piscitelli, Stephen

2014-12-15

GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous injections. This was a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744 was administered as a 200 mg/mL nanosuspension at doses of 100-800 mg IM and 100-400 mg subcutaneous. Eight (6 active and 2 placebo) male and female subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and 4 females, received active 744 LA in cohorts 8 and 9 and underwent rectal and cervicovaginal tissue sampling, respectively. Plasma pharmacokinetic sampling was performed for a minimum of 12 weeks or until 744 concentrations were ≤0.1 μg/mL. Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8 (cohort 8) and weeks 4 and 12 (cohort 9). 744 LA was generally safe and well tolerated after single injections. A majority of subjects reported injection site reactions, all graded as mild in intensity. Plasma concentration-time profiles were prolonged with measureable concentrations up to 52 weeks after dosing. 744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16 weeks. Rectal and cervicovaginal tissue concentrations ranged from injection has potential application as a monthly or less frequent HIV treatment or prevention agent.

Effects of co-administration of fluoxetine or tianeptine with metyrapone on immobility time and plasma corticosterone concentration in rats subjected to the forced swim test.

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Rogóz, Zofia; Skuza, Grazyna; Leśkiewicz, Monika; Budziszewska, Bogusława

2008-01-01

Major depression is frequently associated with hyperactivity of the hypothalamic-pituitary-adrenocortical axis, and glucocorticoid synthesis inhibitors have been shown to exert antidepressant action. The aim of the present study was to examine the effect of co-administration of fluoxetine or tianeptine with metyrapone on immobility time and plasma corticosterone concentration in male Wistar rats subjected to the forced swim test. Metyrapone alone (50 mg/kg, but not 25 mg/kg) reduced the immobility time of rats in the forced swim test; moreover, both doses tested (25 and 50 mg/kg), dose-dependently decreased the stress-induced plasma corticosterone concentration. Joint administration of fluoxetine or tianeptine (10 mg/kg) and metyrapone (25 mg/kg - a dose inactive per se) exhibited antidepressant-like activity in the forced swim test in rats. WAY 100636 (a 5-HT(1A) antagonist), but not prazosin (an alpha(1)-adrenergic antagonist), used in doses ineffective in the forced swim test, inhibited the antidepressant-like effect induced by co-administration of fluoxetine or tianeptine with metyrapone (25 mg/kg). Combined treatment of fluoxetine or tianeptine and metyrapone inhibited stress-induced corticosterone secretion to a similar extent as metyrapone alone. The obtained results indicate that metyrapone potentiates the antidepressant-like activity of fluoxetine or tianeptine and that, among other mechanisms, 5-HT(1A) receptors may play some role in this effect. Moreover, metyrapone exerts a beneficial effect on the stress-induced increase in plasma corticosterone concentration. These findings suggest that the co-administration of metyrapone and an antidepressant drug may be useful for the treatment of drug-resistant depression and/or depression associated with a high cortisol level.

Concentration-related metabolic rate and behavioral thermoregulatory adaptations to serial administrations of nitrous oxide in rats

Science.gov (United States)

2018-01-01

Background Initial administration of ≥60% nitrous oxide (N2O) to rats evokes hypothermia, but after repeated administrations the gas instead evokes hyperthermia. This sign reversal is driven mainly by increased heat production. To determine whether rats will behaviorally oppose or assist the development of hyperthermia, we previously performed thermal gradient testing. Inhalation of N2O at ≥60% causes rats to select cooler ambient temperatures both during initial administrations and during subsequent administrations in which the hyperthermic state exists. Thus, an available behavioral response opposes (but does not completely prevent) the acquired hyperthermia that develops over repeated high-concentration N2O administrations. However, recreational and clinical uses of N2O span a wide range of concentrations. Therefore, we sought to determine the thermoregulatory adaptations to chronic N2O administration over a wide range of concentrations. Methods This study had two phases. In the first phase we adapted rats to twelve 3-h N2O administrations at either 0%, 15%, 30%, 45%, 60% or 75% N2O (n = 12 per group); outcomes were core temperature (via telemetry) and heat production (via respirometry). In the second phase, we used a thermal gradient (range 8°C—38°C) to assess each adapted group’s thermal preference, core temperature and locomotion on a single occasion during N2O inhalation at the assigned concentration. Results In phase 1, repeated N2O administrations led to dose related hyperthermic and hypermetabolic states during inhalation of ≥45% N2O compared to controls (≥ 30% N2O compared to baseline). In phase 2, rats in these groups selected cooler ambient temperatures during N2O inhalation but still developed some hyperthermia. However, a concentration-related increase of locomotion was evident in the gradient, and theoretical calculations and regression analyses both suggest that locomotion contributed to the residual hyperthermia. Conclusions Acquired

Effect of low-dose atropine administration on dobutamine dose requirement in horses anesthetized with detomidine and halothane.

Science.gov (United States)

Weil, A B; Keegan, R D; Greene, S A

1997-12-01

To determine whether a low dose of atropine is associated with decreased requirement for cardiovascular supportive treatment in horses given detomidine prior to maintenance of general anesthesia with halothane. 3 groups of 10 healthy horses. Detomidine (20 micrograms/kg of body weight, i.m.) was administered to all 30 horses. Then, 10 horses received atropine (0.006 mg/kg, i.v.) 1 hour after detomidine administration, 10 horses received atropine (0.012 mg/kg, i.m.) at the time of detomidine administration, and 10 horses served as a control group. Heart rate was measured prior to detomidine administration and at fixed intervals throughout anesthesia. The dobutamine infusion rate necessary to maintain mean arterial blood pressure between 70 and 80 mm of Hg was recorded. Systemic blood pressures, end-tidal halothane, end-tidal CO2, and arterial blood gas tensions were measured at fixed intervals. Mean heart rate was higher among horses receiving atropine i.v. or i.m., compared with that in control horses. Horses that received atropine i.v. had higher systemic arterial blood pressure and required a lower dobutamine infusion rate than did horses of the other groups. Detomidine-treated, halothane-anesthetized horses given atropine i.v. required less dobutamine, compared with horses receiving or not receiving atropine i.m. Complications, such as colic and dysrhythmias, from use of higher doses of atropine, were not observed at this lower dose of atropine. i.v. administration of a low dose of atropine prior to induction of general anesthesia may result in improved blood pressure in horses that have received detomidine before anesthesia with halothane.

Estimation of chloroform inhalation dose by other routes based on the relationship of area under the blood concentration-time curve (AUC)-inhalation dose to chloroform distribution in the blood of rats.

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Take, Makoto; Takeuchi, Tetsuya; Haresaku, Mitsuru; Matsumoto, Michiharu; Nagano, Kasuke; Yamamoto, Seigo; Takamura-Enya, Takeji; Fukushima, Shoji

2014-01-01

The present study investigated the time-course changes of concentration of chloroform (CHCl3) in the blood during and after exposure of male rats to CHCl3 by inhalation. Increasing the dose of CHCl3 in the inhalation exposed groups caused a commensurate increase in the concentration of CHCl3 in the blood and the area under the blood concentration-time curve (AUC). There was good correlation (r = 0.988) between the inhalation dose and the AUC/kg body weight. Based on the AUC/kg body weight-inhalation dose curve and the AUC/kg body weight after oral administration, inhalation equivalent doses of orally administered CHCl3 were calculated. Calculation of inhalation equivalent doses allows the body burden due to CHCl3 by inhalation exposure and oral exposure to be directly compared. This type of comparison facilitates risk assessment in humans exposed to CHCl3 by different routes. Our results indicate that when calculating inhalation equivalent doses of CHCl3, it is critical to include the AUC from the exposure period in addition to the AUC after the end of the exposure period. Thus, studies which measure the concentration of volatile organic compounds in the blood during the inhalation exposure period are crucial. The data reported here makes an important contribution to the physiologically based pharmacokinetic (PBPK) database of CHCl3 in rodents.

Experimental study, in rat wistar, of cadmium distribution and elimination as a function of administration route. Cadmium 109 maximum permissible concentration

International Nuclear Information System (INIS)

Valero, Marc.

1979-01-01

The absorption and the elimination of cadmium have been investigated in rats wistar after oral administration or after inhalation. Before studying gastro-intestinal absorption, it appeared necessary to precise acute toxicity of orally administred cadmium. The distribution of cadmium within organes was determined following a single or multiple oral doses, and we specially studied retention of a Cd dose ingested after several weeks of treatment with Cd-Acetate. Pulmonary and gastro-intestinal absorption of cadmium after ihalation of Cd-microparticles were studied. Data obtained from these studies on rats and extrapolated to man were used to calculate mximum permissible concentration (M.P.C.) of Cd-109 in water and in air [fr

Caffeine Citrate Dosing Adjustments to Assure Stable Caffeine Concentrations in Preterm Neonates.

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Koch, Gilbert; Datta, Alexandre N; Jost, Kerstin; Schulzke, Sven M; van den Anker, John; Pfister, Marc

2017-12-01

To identify dosing strategies that will assure stable caffeine concentrations in preterm neonates despite changing caffeine clearance during the first 8 weeks of life. A 3-step simulation approach was used to compute caffeine doses that would achieve stable caffeine concentrations in the first 8 weeks after birth: (1) a mathematical weight change model was developed based on published weight distribution data; (2) a pharmacokinetic model was developed based on published models that accounts for individual body weight, postnatal, and gestational age on caffeine clearance and volume of distribution; and (3) caffeine concentrations were simulated for different dosing regimens. A standard dosing regimen of caffeine citrate (using a 20 mg/kg loading dose and 5 mg/kg/day maintenance dose) is associated with a maximal trough caffeine concentration of 15 mg/L after 1 week of treatment. However, trough concentrations subsequently exhibit a clinically relevant decrease because of increasing clearance. Model-based simulations indicate that an adjusted maintenance dose of 6 mg/kg/day in the second week, 7 mg/kg/day in the third to fourth week and 8 mg/kg/day in the fifth to eighth week assures stable caffeine concentrations with a target trough concentration of 15 mg/L. To assure stable caffeine concentrations during the first 8 weeks of life, the caffeine citrate maintenance dose needs to be increased by 1 mg/kg every 1-2 weeks. These simple adjustments are expected to maintain exposure to stable caffeine concentrations throughout this important developmental period and might enhance both the short- and long-term beneficial effects of caffeine treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacokinetic/pharmacodynamic modeling of benazepril and benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses.

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Serrano-Rodríguez, Juan Manuel; Gómez-Díez, Manuel; Esgueva, María; Castejón-Riber, Cristina; Mena-Bravo, Antonio; Priego-Capote, Feliciano; Ayala, Nahúm; Caballero, Juan Manuel Serrano; Muñoz, Ana

2017-10-01

Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin-converting enzyme inhibitor (ACEI) benazeprilat have not been evaluated in horses. This study was designed to establish PK profiles for benazepril and benazeprilat after intravenous (IV) and oral (PO) administration of benazepril using a PK/PD model. This study also aims to determine the effects of benazeprilat on serum angiotensin converting enzyme (ACE), selecting the most appropriate dose that suppresses ACE activity. Six healthy horses in a crossover design received IV benazepril at 0.50mg/kg and PO at doses 0 (placebo), 0.25, 0.50 and 1.00mg/kg. Blood pressures (BP) were measured and blood samples were obtained at different times in order to measure serum drug concentrations and serum ACE activity, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and spectrophotometry, respectively. Systemic bioavailability of benazeprilat after PO benazepril was 3-4%. Maximum ACE inhibitions from baseline were 99.63% (IV benazepril), 6.77% (placebo) and 78.91%, 85.74% and 89.51% (for the three PO benazepril doses). Significant differences in BP were not found. Although oral availability was low, benazeprilat 1.00mg/kg, reached sufficient serum concentrations to induce long lasting serum ACE inhibitions (between 88 and 50%) for the first 48h. Additional research on benazepril administration in equine patients is indicated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prediction of Optimal Reversal Dose of Sugammadex after Rocuronium Administration in Adult Surgical Patients

Directory of Open Access Journals (Sweden)

Shigeaki Otomo

2014-01-01

Full Text Available The objective of this study was to determine the point after sugammadex administration at which sufficient or insufficient dose could be determined, using first twitch height of train-of-four (T1 height or train-of-four ratio (TOFR as indicators. Groups A and B received 1 mg/kg and 0.5 mg/kg of sugammadex, respectively, as a first dose when the second twitch reappeared in train-of-four stimulation, and Groups C and D received 1 mg/kg and 0.5 mg/kg of sugammadex, respectively, as the first dose at posttetanic counts 1–3. Five minutes after the first dose, an additional 1 mg/kg of sugammadex was administered and changes in T1 height and TOFR were observed. Patients were divided into a recovered group and a partly recovered group, based on percentage changes in T1 height after additional dosing. T1 height and TOFR during the 5 min after first dose were then compared. In the recovered group, TOFR exceeded 90% in all patients at 3 min after sugammadex administration. In the partly recovered group, none of the patients had a TOFR above 90% at 3 min after sugammadex administration. An additional dose of sugammadex can be considered unnecessary if the train-of-four ratio is ≥90% at 3 min after sugammadex administration. This trial is registered with UMIN000007245.

Absence of hydrocortisone from cytoplasmic hormone-protein complexes formed in vivo after administration of biologically active doses of [3H] hydrocortisone

International Nuclear Information System (INIS)

Voigt, J.; Grote, H.; Sekeris, C.E.

1981-01-01

After administration of [ 3 H] hydrocortisone to adrenalectomized rats, hormone-protein complexes were isolated from liver cytosol by DEAE-cellulose chromatography. After application of biologically active and inactive doses of hydrocortisone five binding components were detected eluting at the same salt concentrations as the hormone-protein complexes observed after incubation of cytosol with [ 3 H] hydrocortisone in vitro. The isolated hormone-protein fractions were acidified and extracted with ethylacetate and the steroids were analyzed by thin-layer chromatography. No significant amount of hydrocortisone could be detected in any of the complexes formed in vivo 5-60 min after administration of biologically active doses of hydrocortisone. 3xi,11β,17α,20xi, 21-Pentahydroxypregnane, steroidal carboxy acids, glucuronides and a very polar conjugate of hydrocortisone were found in the different fractions. After an in vivo dose of hydrocortisone of about 1/5000th of the minimal dose required for enzyme induction, hydrocortisone could be found in all the cytoplasmic hormone-protein complexes formed. In contrast to the cytoplasmic hormone-protein complexes, hydrocortisone could be readily demonstrated in nuclei isolated after the administration of biologically active doses of hormone, although acid metabolites were found to represent the main part of the radioactive compounds present in the nuclei. These acid metabolites were located in the nuclear envelope. (orig.)

Estimation of the total effective dose from low-dose CT scans and radiopharmaceutical administrations delivered to patients undergoing SPECT/CT explorations

International Nuclear Information System (INIS)

Montes, C.; Hernandez, J.; Gomez-Caminero, F.; Garcia, S.; Martin, C.; Rosero, A.; Tamayo, P.

2013-01-01

Hybrid imaging, such as single photon emission computed tomography (SPECT)/CT, is used in routine clinical practice, allowing coregistered images of the functional and structural information provided by the two imaging modalities. However, this multimodality imaging may mean that patients are exposed to a higher radiation dose than those receiving SPECT alone. The study aimed to determine the radiation exposure of patients who had undergone SPECT/CT examinations and to relate this to the Background Equivalent Radiation Time (BERT). 145 SPECT/CT studies were used to estimate the total effective dose to patients due to both radiopharmaceutical administrations and low-dose CT scans. The CT contribution was estimated by the Dose-Length Product method. Specific conversion coefficients were calculated for SPECT explorations. The radiation dose from low-dose CTs ranged between 0.6 mSv for head and neck CT and 2.6 mSv for whole body CT scan, representing a maximum of 1 year of background radiation exposure. These values represent a decrease of 80-85% with respect to the radiation dose from diagnostic CT. The radiation exposure from radiopharmaceutical administration varied from 2.1 mSv for stress myocardial perfusion SPECT to 26 mSv for gallium SPECT in patients with lymphoma. The BERT ranged from 1 to 11 years. The contribution of low-dose CT scans to the total radiation dose to patients undergoing SPECT/CT examinations is relatively low compared with the effective dose from radiopharmaceutical administration. When a CT scan is only acquired for anatomical localization and attenuation correction, low-dose CT scan is justified on the basis of its lower dose. (author)

Endogenous concentrations, pharmacokinetics, and selected pharmacodynamic effects of a single dose of exogenous GABA in horses.

Science.gov (United States)

Knych, H K; Steinmetz, S J; McKemie, D S

2015-04-01

The anti-anxiety and calming effects following activation of the GABA receptor have been exploited in performance horses by administering products containing GABA. The primary goal of the study reported here was to describe endogenous concentrations of GABA in horses and the pharmacokinetics, selected pharmacodynamic effects, and CSF concentrations following administration of a GABA-containing product. The mean (±SD) endogenous GABA level was 36.4 ± 12.5 ng/mL (n = 147). Sixteen of these horses received a single intravenous and oral dose of GABA (1650 mg). Blood, urine, and cerebrospinal fluid (n = 2) samples were collected at time 0 and at various times for up to 48 h and analyzed using LC-MS. Plasma clearance and volume of distribution was 155.6 and 147.6 L/h and 0.154 and 7.39 L for the central and peripheral compartments, respectively. Terminal elimination half-life was 22.1 (intravenous) and 25.1 (oral) min. Oral bioavailability was 9.81%. Urine GABA concentrations peaked rapidly returning to baseline levels by 3 h. Horses appeared behaviorally unaffected following oral administration, while sedative-like changes following intravenous administration were transient. Heart rate was increased for 1 h postintravenous administration, and gastrointestinal sounds decreased for approximately 30 min following both intravenous and oral administration. Based on a limited number of horses and time points, exogenously administered GABA does not appear to enter the CSF to an appreciable extent. © 2014 John Wiley & Sons Ltd.

Relationship between human tooth enamel free radical concentration and radiation dose

International Nuclear Information System (INIS)

Zhou Yongzeng; Wang Jiadong; Jia Xiaomei; Wu Ke; Cong Jianbo; Sun Cunpu

1999-01-01

Free radical concentrations of 25 adult tooth enamel samples were measured by electron spin resonance (ESR) technique in this paper, and the relationship between free radical concentration of tooth enamel and radiation dose was also investigated. In the 25 adult enamel samples they are 16 male samples and 9 female samples, Ages of tooth donors range from 18-41 years. Difference in background ESR signal intensity between male and female samples was no observed; free radical concentration (or increment of radiation-induced free radical concentration) in tooth enamel increases linearly with increasing of radiation dose. In the case of radiation accident, the study results of this paper could be applied to dose estimation when conditions of ESR measurement of exposed individual tooth enamel are similar to measurement conditions of dose-effect calibration curve in this paper

Estimate of the absorbed dose in the mouse organs and tissues after tritium administration

International Nuclear Information System (INIS)

Saito, Masahiro

2000-01-01

Chronic and accidental release of tritium from future fusion facilities may cause some extent of hazardous effect to the public health. Various experiments using small animals such as mice have been performed to mimic the dose accumulation due to tritium intake by the human body. An difficulty in such animal experiments using small animals is that it is rather difficult to administer tritium orally and estimate the dose to small organs or tissues. In the course of our study, a simple method to administer THO and T-labeled amino acids orally to the mouse was dictated and dose accumulation in various organs and tissues was determined. The tritium retention in the bone marrow was also determined using the micro-centrifuge method. Throughout our experiment, colony-bred DDY mice were used. The 8-10 week old male mice were orally and intraperitoneally administered THO water or T-amino acids mixture solution. For the purpose of oral administration, a 10 μl aliquot of T-containing saline solution was placed on the tongue of the mice using an automatic micropipette. At various times after tritium administration, the animals were sacrificed and the amount of tritium in various tissues and organs including bone marrow was examined. Dose accumulation pattern after THO intake and T-amino acids was compared between intraperitoneal injection and oral administration. The accumulated dose after oral administration of THO exhibited a tendency to be 10-20% higher than after intraperitoneal injection. The bone marrow dose after oral intake of THO was found to be lower than the doses to urine, blood, liver and testis. In contrast, the blood dose gave a conservative estimate for the dose to the other tissues and organs. (author)

Assessment of fetal activity concentration and fetal dose for selected radionuclides based on animal and human data

International Nuclear Information System (INIS)

Roedler, H.D.

1987-01-01

Biokinetic data of selected radionuclide compounds from investigations in man and animal were taken from literature references with the purpose to provide a basis for a comparative assessment of fetal and adult radiation doses after intake or administration of radionuclides. The following ratios of fetal to adult doses were derived from human data: 0.5 for caesium 137 and total body, 2.3 for iron 59 and liver, 0.06 - 0.3 - 1.1 for iodine 131 and thyroid, and 0.1 - 0.3 for strontium 90 and bone. The ratios of activity concentrations in fetal and adult tissues are of considerable variability - up to three orders of magnitude. Further studies on fetal and adult biokinetics specifically designed for comparative dose assessment are indispensable. 106 refs.; 6 tabs

Nicotine dose-concentration relationship and pregnancy outcomes in rat: Biologic plausibility and implications for future research

International Nuclear Information System (INIS)

Hussein, Jabeen; Farkas, Svetlana; MacKinnon, Yolanda; Ariano, Robert E.; Sitar, Daniel S.; Hasan, Shabih U.

2007-01-01

Cigarette smoke (CS) exposure during pregnancy can lead to profound adverse effects on fetal development. Although CS contains several thousand chemicals, nicotine has been widely used as its surrogate as well as in its own right as a neuroteratogen. The justification for the route and dose of nicotine administration is largely based on inferential data suggesting that nicotine 6 mg/kg/day infused continuously via osmotic mini pumps (OMP) would mimic maternal CS exposure. We provide evidence that 6 mg/kg/day nicotine dose as commonly administered to pregnant rats leads to plasma nicotine concentrations that are 3-10-fold higher than those observed in moderate to heavy smokers and pregnant mothers, respectively. Furthermore, the cumulative daily nicotine dose exceeds by several hundred fold the amount consumed by human heavy smokers. Our study does not support the widely accepted notion that regardless of the nicotine dose, a linear nicotine dose-concentration relationship exists in a steady-state OMP model. We also show that total nicotine clearance increases with advancing pregnancy but no significant change is observed between the 2nd and 3rd trimester. Furthermore, nicotine infusion even at this extremely high dose has little effect on a number of maternal and fetal biologic variables and pregnancy outcome suggesting that CS constituents other than nicotine mediate the fetal growth restriction in infants born to smoking mothers. Our current study has major implications for translational research in developmental toxicology and pharmacotherapy using nicotine replacement treatment as an aid to cessation of cigarette smoking in pregnant mothers

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. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

Pharmacokinetics after intravenous, subcutaneous, and oral administration of enrofloxacin to alpacas.

Science.gov (United States)

Gandolf, A Rae; Papich, Mark G; Bringardner, Amy B; Atkinson, Mark W

2005-05-01

To determine plasma concentrations of enrofloxacin and the active metabolite ciprofloxacin after p.o, s.c., and i.v. administration of enrofloxacin to alpacas. 6 adult female alpacas. A crossover design was used for administration of 3 single-dose treatments of enrofloxacin to alpacas, which was followed by an observational 14-day multiple-dose regimen. Single-dose treatments consisted of i.v. and s.c. administration of injectable enrofloxacin (5 mg/kg) and p.o administration of enrofloxacin tablets (10 mg/kg) dissolved in grain to form a slurry. Plasma enrofloxacin concentrations were measured by use of high-performance liquid chromatography. The multiple-dose regimen consisted of feeding a mixture of crushed and moistened enrofloxacin tablets mixed with grain. Behavior, appetite, and fecal quality were monitored throughout the 14-day treatment regimen and for 71 additional days following treatment. Mean half-life following i.v., s.c., and p.o. administration was 11.2, 8.7, and 16.1 hours, respectively. For s.c. and p.o administration, mean total systemic availability was 90.18% and 29.31%, respectively; mean maximum plasma concentration was 3.79 and 1.81 microg/mL, respectively; and area under the curve (AUC) was 50.05 and 33.97 (microg x h)/mL, respectively. The s.c. or p.o administration of a single dose of enrofloxacin yielded a ratio for AUC to minimum inhibitory concentration > 100 for many grampositive and gram-negative bacterial pathogens common to camelids. Conclusions and Clinical Relevance-The administration of enrofloxacin (5 mg/kg, s.c., or 10 mg/kg, p.o) may be appropriate for antimicrobial treatment of alpacas.

Pharmacokinetics of a concentrated buprenorphine formulation in red-tailed hawks (Buteo jamaicensis).

Science.gov (United States)

Gleeson, Molly D; Guzman, David Sanchez-Migallon; Knych, Heather K; Kass, Philip H; Drazenovich, Tracy L; Hawkins, Michelle G

2018-01-01

OBJECTIVE To determine the pharmacokinetics and sedative effects of 2 doses of a concentrated buprenorphine formulation after SC administration to red-tailed hawks (Buteo jamaicensis). ANIMALS 6 adult red-tailed hawks. PROCEDURES Concentrated buprenorphine (0.3 mg/kg, SC) was administered to all birds. Blood samples were collected at 10 time points over 24 hours after drug administration to determine plasma buprenorphine concentrations. After a 4-week washout period, the same birds received the same formulation at a higher dose (1.8 mg/kg, SC), and blood samples were collected at 13 time points over 96 hours. Hawks were monitored for adverse effects and assigned agitation-sedation scores at each sample collection time. Plasma buprenorphine concentrations were quantified by liquid chromatography-tandem mass spectrometry. RESULTS Mean time to maximum plasma buprenorphine concentration was 7.2 minutes and 26.1 minutes after administration of the 0.3-mg/kg and 1.8-mg/kg doses, respectively. Plasma buprenorphine concentrations were > 1 ng/mL for mean durations of 24 and 48 hours after low- and high-dose administration, respectively. Mean elimination half-life was 6.23 hours for the low dose and 7.84 hours for the high dose. Mean agitation-sedation scores were higher (indicating some degree of sedation) than the baseline values for 24 hours at both doses. No clinically important adverse effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE Concentrated buprenorphine was rapidly absorbed, and plasma drug concentrations considered to have analgesic effects in other raptor species were maintained for extended periods. Most birds had mild to moderate sedation. Additional studies are needed to evaluate the pharmacodynamics of these doses of concentrated buprenorphine in red-tailed hawks.

Plasma concentrations of fenbendazole (FBZ and oxfendazole in alpacas (Lama pacos after single intravenous and oral dosing of FBZ

Directory of Open Access Journals (Sweden)

Lakritz J

2015-02-01

Full Text Available Jeffrey Lakritz,1 Daniel Linden,2 David E Anderson,3 Terri A Specht4 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA; 2Department of Agriculture and Engineering Technologies, College of Food, Agriculture and Environmental Sciences, The Ohio State University, Wooster, OH, USA; 3Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA; 4Four Star Veterinary Service, Chickasaw, OH, USA Abstract: The objective of this study was to determine plasma pharmacokinetics and bioavailability of fenbendazole (FBZ and oxfendazole (OFZ after intravenous (iv and oral administrations of FBZ (5 mg/kg to alpacas. Plasma concentrations of FBZ and OFZ after administration of FBZ iv and orally (5 mg/kg were determined by high-performance liquid chromatography with ultraviolet detection. Total clearance (CL of FBZ was 16.5±4 mL/kg/min (range: 4–31 mL/kg/min, and steady-state volume of distribution (Vdss was 3.3±1 L/kg (range: 1.7–7.4 L/kg. The terminal phase half-life of FBZ after iv administration was 5.9±3.8 hours (range: 0.8–20 hours. After oral administration, the FBZ terminal phase half-life was 23±5 hours (range: 9–37 hours and the systemic bioavailability of FBZ was 16%±6% (range: 1%–41%. Peak FBZ concentrations after oral administration were 0.13±0.05 µg/mL (range: 0.05–0.28 µg/mL at 10 hours (range: 8–12 hours. Peak plasma OFZ concentrations after oral dosing with FBZ (5 mg/kg were 0.14±0.05 µg/mL (0.05–0.3 µg/mL at 24±7 hours (range: 12–48 hours. FBZ clearance is lower in comparison to that of other species. Systemic availability of FBZ after oral administration is low after oral dosing. Metabolites of FBZ produced by alpacas are similar to those observed in other species. Keywords: bioavailability, benzimidazoles, camelid, pharmacokinetics

Effect of weekly high-dose vitamin D3 supplementation on serum cholecalciferol concentrations in pregnant women.

Science.gov (United States)

Dimitris, Michelle C; Perumal, Nandita; Craig-Barnes, Hayley A; Leadley, Michael; Mahmud, Abdullah A; Baqui, Abdullah H; Roth, Daniel E

2016-04-01

Vitamin D status is conventionally defined by the serum concentration of 25-hydroxyvitamin D. However, it has been proposed that the serum cholecalciferol concentration (D3) also determines functional vitamin D sufficiency. The objective of this study was to describe the effect of weekly high-dose vitamin D3 supplementation on inter-dose serum D3 in pregnant women. We conducted a sub-study of a completed randomized double-blind placebo-controlled trial of vitamin D3 (35,000 IU/week) supplementation in late pregnancy (AViDD trial) in Dhaka, Bangladesh. This study included pregnant women enrolled at 26-29 weeks gestation who fully adhered to the prenatal supplement intervention for ≥8 consecutive weeks and for whom serum samples were available for D3 analysis (n=65). Serum D3 was uniformly low at enrolment. Mean D3 increased and was maximal at 1 day after vitamin D dose administration (152.09nmol/L, SD 25.11nmol/L) and remained significantly higher in VitD vs. Pl at 7 days (29.59nmol/L vs. 1.92nmol/L, p=0.007). Daily average of the group mean D3 during the week following dosing was 66.97nmol/L in VitD versus 2.13nmol/L in Pl. In conclusion, serum D3 remained significantly elevated throughout the week following ≥8 consecutive weekly doses of 35,000 IU D3 in pregnant women. However, the clinically significant minimum threshold of serum D3 remains to be established. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of intravenous administration of tramadol hydrochloride on the minimum alveolar concentration of isoflurane in rabbits.

Science.gov (United States)

Egger, Christine M; Souza, Marcy J; Greenacre, Cheryl B; Cox, Sherry K; Rohrbach, Barton W

2009-08-01

To evaluate the effect of IV administration of tramadol hydrochloride on the minimum alveolar concentration of isoflurane (ISOMAC) that prevented purposeful movement of rabbits in response to a noxious stimulus. Six 6- to 12-month-old female New Zealand White rabbits. Anesthesia was induced and maintained with isoflurane in oxygen. A baseline ISOMAC was determined by clamping a pedal digit with sponge forceps until gross purposeful movement was detected or a period of 60 seconds elapsed. Subsequently, tramadol (4.4 mg/kg) was administered IV and the posttreatment ISOMAC (ISOMAC(T)) was measured. Mean +/- SD ISOMAC and ISOMAC(T) values were 2.33 +/- 0.13% and 2.12 +/- 0.17%, respectively. The ISOMAC value decreased by 9 +/- 4% after tramadol was administered. Plasma tramadol and its major metabolite (M1) concentrations at the time of ISOMAC(T) determination varied widely (ranges, 181 to 636 ng/mL and 32 to 61 ng/mL, respectively). Intervals to determination of ISOMAC(T) and plasma tramadol and M1 concentrations were not correlated with percentage change in the ISOMAC. Heart rate decreased significantly immediately after tramadol administration but by 10 minutes afterward was not different from the pretreatment value. Systolic arterial blood pressure decreased to approximately 60 mm Hg for approximately 5 minutes in 3 rabbits after tramadol administration. No adverse effects were detected. As administered, tramadol had a significant but clinically unimportant effect on the ISOMAC in rabbits. Higher doses of tramadol may provide clinically important reductions but may result in a greater degree of cardiovascular depression.

Single-dose and multiple-dose pharmacokinetics and dose proportionality of intravenous and intramuscular HPβCD-diclofenac (Dyloject) compared with other diclofenac formulations.

Science.gov (United States)

Mermelstein, Fred; Hamilton, Douglas A; Wright, Curtis; Lacouture, Peter G; Ramaiya, Atulkumar; Carr, Daniel B

2013-10-01

To evaluate single- and repeated-dose pharmacokinetics (PK) and dose proportionality of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac compared with Voltarol after intravenous (IV) and intramuscular (IM) administration. Study 1: Single-dose randomized four-way crossover study. Study 2: Multiple-dose randomized three-way crossover study. Clinical research center. Healthy adult volunteers. Study 1: Subjects received HPβCD-diclofenac and Voltarol, IV and IM, with a 5-day washout between treatment periods. Study 2: Subjects received two doses of IV HPβCD-diclofenac and oral Cataflam once every 6 hours for four doses with a 48-hour washout period between treatment periods. Study 1: IV HPβCD-diclofenac had a higher peak plasma concentration (Cmax ) and earlier time to reach maximum plasma concentration (Tmax ), but equivalent plasma exposure (area under the curve from time zero to t [AUC0-t ]) to IV Voltarol. The geometric mean ratio of HPβCD-diclofenac (IV) to Voltarol (IV) for AUC0-t was 106.27%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IM) for AUC0-t was 110.91%. The geometric mean ratio of HPβCD-diclofenac (IV) to HPβCD-diclofenac (IM) for AUC0-t was 101.25%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IV) for AUC0-t was 104.96%. Study 2: Cmax for diclofenac was 2904 and 6031 ng/ml after the first IV dose of 18.75 and 37.5 mg HPβCD-diclofenac, respectively, and was 3090 and 5617 ng/ml after the fourth dose, indicating no accumulation. Plasma exposures to 18.75 mg (866 ng·hour/ml) and 37.5 mg (1843 ng·hour/ml) IV HPβCD-diclofenac bracketed that of oral Cataflam 50 mg (1473 ng·hour/ml). Study 1: Bioavailability in terms of AUC after IV administration was equivalent for HPβCD-diclofenac compared with Voltarol and after IM administration of HPβCD-diclofenac and Voltarol. Bioavailability in terms of AUC after IM administration of HPβCD-diclofenac was equivalent to IV administration of HP�

Effect of low dose Lead (Pb) administration on tail immersion test ...

African Journals Online (AJOL)

Effect of low dose Lead (Pb) administration on tail immersion test and ... subtle decline in cognitive function, and adverse reproductive outcome at low blood Pb level. ... Twenty adult Wistar rats of both sexes (weight 150g to 200g) were used.

Effect of Low Dose Lead (Pb) Administration on Tail Immersion Test ...

African Journals Online (AJOL)

olayemitoyin

Effect of Low Dose Lead (Pb) Administration on Tail ... Acute and sub-acute effects of lead are caused by relatively large ... As such, the brain is the organ most studied in lead toxicity. ..... inflammatory Properties of Hydro-alcohol Extract of.

Effect of dose increase or cimetidine co-administration on albendazole bioavailability

NARCIS (Netherlands)

Schipper, H. G.; Koopmans, R. P.; Nagy, J.; Butter, J. J.; Kager, P. A.; van Boxtel, C. J.

2000-01-01

The low bioavailability of albendazole affects the therapeutic response in patients with echinococcosis. Cimetidine co-administration is reported to improve bioavailability. To analyze the assumed dose-dependent bioavailability of albendazole, we administered 5 to 30 mg/kg albendazole to 6 male

Short and long term modulation of tissue minerals concentrations following oral administration of black cumin (Nigella sativa L.) seed oil to laboratory rats.

Science.gov (United States)

Basheer, Irum; Qureshi, Irfan Zia

2018-01-15

Nigella sativa, or commonly called black cumin is a small herb of family Ranunculaceae is a well-known medicinal plant but its effects on tissue mineral concentrations of animal bodies is unknown. To study the effect of oral administration of fixed oil of black cumin seeds on tissues mineral content using laboratory rats as experimental model. Experimental animals were exposed to two oral doses of seed oil (60 and 120 ml kg -1 body weight). Short- and long term experiments lasted 24 h and 60 days respectively, with three replicates each. Oil extracted from black cumin seeds was subjected to GC-MS to identify chemical components. Following the wet digestion in nitric acid, samples of whole blood and organs of rats were subjected to atomic absorption spectrophotometry for determination of elements concentrations. Data were compared statistically at p < .05. Compared to control, Cr, Mn, Ni, Cu, Zn showed decrease, whereas Co, Na, Mg and K demonstrated increase, but Ca showed both increase and decrease in most of the tissues upon short term exposure to low and high doses of black cumin oil. During long term exposure, Cr, Fe, Mn, Cu exhibited decrease; Co, Na, Mg and Ca concentrations demonstrated an upregulation, whereas Ni and Zn showed increase and decrease in most of the tissues. Comparison of short term with long term experiments at low dose revealed increases in Fe, Zn, Cu, Mg, K and Ca, a decrease in Cr, Mn, Ni and Cu in most tissues, but both increase and decrease in Na. At high dose, an increase occurred in Fe, Ni, Zn, K, Ca, Mg, a decrease in Cr, while both increase and decrease in Cu, Co and Na concentrations. Our study demonstrates that oral administration of black cumin seeds oil to laboratory rats significantly alters tissue trace elements and electrolytes concentrations. The study appears beneficial but indicates modulatory role of black cumin oil as regards mineral metabolism with far reaching implications in health and disease. Copyright © 2017

Concentration - dose - risk computer code

International Nuclear Information System (INIS)

Frujinoiu, C.; Preda, M.

1997-01-01

Generally, the society is less willing in promoting remedial actions in case of low level chronic exposure situations. Radon in dwellings and workplaces is a case connected to chronic exposure. Apart from radon, the solely source on which the international community agreed for setting action levels, there are other numerous sources technically modified by man that can generate chronic exposure. Even if the nuclear installations are the most relevant, we are surrounded by 'man-made radioactivity' such as: mining industry, coal-fired power plants and fertilizer industry. The operating of an installation even within 'normal limits' could generate chronic exposure due to accumulation of the pollutants after a definite time. This asymptotic proclivity to a constant level define a steady-state concentration that represents a characteristic of the source's presence in the environment. The paper presents a methodology and a code package that derives sequentially the steady-state concentration, doses, detriments, as well as the costs of the effects of installation operation in a given environment. (authors)

MLSOIL and DFSOIL - computer codes to estimate effective ground surface concentrations for dose computations

International Nuclear Information System (INIS)

Sjoreen, A.L.; Kocher, D.C.; Killough, G.G.; Miller, C.W.

1984-11-01

This report is a user's manual for MLSOIL (Multiple Layer SOIL model) and DFSOIL (Dose Factors for MLSOIL) and a documentation of the computational methods used in those two computer codes. MLSOIL calculates an effective ground surface concentration to be used in computations of external doses. This effective ground surface concentration is equal to (the computed dose in air from the concentration in the soil layers)/(the dose factor for computing dose in air from a plane). MLSOIL implements a five compartment linear-transfer model to calculate the concentrations of radionuclides in the soil following deposition on the ground surface from the atmosphere. The model considers leaching through the soil as well as radioactive decay and buildup. The element-specific transfer coefficients used in this model are a function of the k/sub d/ and environmental parameters. DFSOIL calculates the dose in air per unit concentration at 1 m above the ground from each of the five soil layers used in MLSOIL and the dose per unit concentration from an infinite plane source. MLSOIL and DFSOIL have been written to be part of the Computerized Radiological Risk Investigation System (CRRIS) which is designed for assessments of the health effects of airborne releases of radionuclides. 31 references, 3 figures, 4 tables

Effect of experimental quinine administration on plasma levels of ...

African Journals Online (AJOL)

Six hours after the last dose administration, blood samples were withdrawn for the determination of plasma levels of hemoglobin and methemoglobin. Plasma hemoglobin concentration increased from 11.55 +0.32 g/100ml to a critical value of 14.30 g/100ml from the control to 0.08 g/kg dose administration. A further increase ...

Disposition of the anti-ulcer medications ranitidine, cimetidine, and omeprazole following administration of multiple doses to exercised Thoroughbred horses.

Science.gov (United States)

Knych, H K; Stanley, S D; Arthur, R M; McKemie, D S

2017-01-01

The use of anti-ulcer medications, such as cimetidine, ranitidine, and omeprazole, is common in performance horses. The use of these drugs is regulated in performance horses, and as such a withdrawal time is necessary prior to competition to avoid a medication violation. To the authors' knowledge, there are no reports in the literature describing repeated oral administrations of these drugs in the horse to determine a regulatory threshold and related withdrawal time recommendations. Therefore, the objective of the current study was to describe the disposition and elimination pharmacokinetics of these anti-ulcer medications following oral administration to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 20 mg/kg BID of cimetidine or 8 mg/kg BID of ranitidine, both for seven doses or 2.28 g of omeprazole SID for four doses. Blood samples were collected, serum drug concentrations were determined, and elimination pharmacokinetic parameters were calculated. The serum elimination half-life was 7.05 ± 1.02, 7.43 ± 0.851 and 3.94 ± 1.04 h for cimetidine, ranitidine, and omeprazole, respectively. Serum cimetidine and ranitidine concentrations were above the LOQ and omeprazole and omeprazole sulfide below the LOQ in all horses studied upon termination of sample collection. © 2016 John Wiley & Sons Ltd.

Dose- and time-dependent changes in tissue levels of tetrabromobisphenol A (TBBPA and its sulfate and glucuronide conjugates following repeated administration to female Wistar Han Rats

Directory of Open Access Journals (Sweden)

S.J. Borghoff

Full Text Available Tetrabromobisphenol A (TBBPA, a nongenotoxic flame retardant, causes uterine tumors in female rats. A proposed mode of action (MoA for these tumors involves an increase in the bioavailability of estradiol as a result of TBBPA inhibiting estrogen sulfotransferases (ES, the enzymes responsible for inactivating and enhancing the elimination of estradiol. The objective of this study was to evaluate the effect of dose and repeated administration of TBBPA on the level of TBBPA, TBBPA-glucuronide (GA and TBBPA-sulfate (S conjugates in plasma, liver and uterus of female Wistar Han rats administered TBBPA (50, 100, 250, 500 or 1000 mg/kg for 28 consecutive days. In accordance with this objective, TBBPA sulfation was used as a surrogate for evaluating the potential for estradiol sulfation to be limited at high dose levels of TBBPA. Blood samples were collected at 4 and 8 h post-dosing on study day 7, 14, and 28, while liver and uterus were collected at the same time points following 28 days of dosing. Tissue samples were analyzed for TBBPA, TBBPA-GA and TBBPA-S by LC–MS/MS. A dose-related increase in the concentration of all three analytes occurred in plasma (day 7, 14, and 28 as well as liver and uterus tissue (day 28 at both 4 and 8 h post dose. The plasma concentration of TBBPA-GA and TBBPA-S was higher in animals dosed for 28 days compared to those dosed for 7 or 14 days showing an increase in systemic circulation of these conjugates with repeated administration. The balance of these conjugates was also different in tissues with TBBPA-S > TBBPA-GA at high doses in the liver and TBBPA-GA > TBBPA-S in both plasma and uterus. In all three tissues the ratio of TBBPA-S/TBBPA-GA showed a decreasing trend with dose, suggesting that at high TBBPA dose levels sulfation of TBBPA becomes limited. This effect was most apparent in the liver and plasma at 28 days of administration. Together these data show that administration of high doses of TBBPA

The concentrations of clinafloxacin in alveolar macrophages, epithelial lining fluid, bronchial mucosa and serum after administration of single 200 mg oral doses to patients undergoing fibre-optic bronchoscopy.

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Honeybourne, D; Andrews, J M; Cunningham, B; Jevons, G; Wise, R

1999-01-01

The concentrations of clinafloxacin were measured in serum, bronchial mucosa, alveolar macrophages and epithelial lining fluid after single 200 mg oral doses of clinafloxacin had been administered to 15 subjects who were undergoing bronchoscopy. Concentrations were measured using a microbiological assay method. Mean concentrations in serum, bronchial mucosa, alveolar macrophages and epithelial lining fluid at a mean of 1.27 h post-dose were 1.54, 2.65, 15.60 and 2.71 mg/L respectively. These site concentrations exceeded the MIC90 for common respiratory pathogens and indicate that clinafloxacin is likely to be effective in the treatment of a wide range of respiratory tract infections.

Pharmacokinetic properties of methadone hydrochloride after single intramuscular administration in adult dairy goats.

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Kock, M; Thompson, E; Vulliet, P R; Brooks, D L

1994-10-01

Pharmacokinetic parameters of methadone were studied in adult dairy goats. Five goats were each given methadone hydrochloride as a single 0.2 mg/kg of body weight dosage by intramuscular (IM) administration. Plasma methadone concentrations were determined for 96 h after dosing. Plasma methadone concentrations after IM administration were best described by an open one-compartment model. Overall elimination half-life (t1/2) was 1.38 h. Peak plasma concentrations were reached 0.25 h after dosing, and the actual plasma concentration averaged 37.8 ng/ml (SD = 12.76) at that time. The data obtained from this study suggest that plasma concentrations, similar to those that are analgesic in humans, can be achieved after IM administration of methadone at a dose rate of 0.2 mg/kg of body weight. In addition, these plasma concentrations can be maintained for up to 3 h after a single injection and, therefore, may provide satisfactory analgesia for such period.

Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain

International Nuclear Information System (INIS)

Ali, S.F.; Newport, G.D.; Scallet, A.C.; Gee, K.W.; Paule, M.G.; Brown, R.M.; Slikker, W. Jr.

1989-01-01

THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the rat brain. In Experiment 1, male Sprague-Dawley rats were gavaged with vehicle, 10 or 20 mg THC/kg body weight daily, 5 days/week for 90 days. Animals were killed either 24 hours or two months after the last dose. Brains were dissected into different regions for neurochemical analyses. Two months after the cessation of chronic administration, there was a significant decrease in GABA receptor binding in the hippocampus of animals in the high dose group. However, no other significant changes were found in neurotransmitter receptor binding characteristics in the hippocampus or in neurotransmitter concentrations in the caudate nucleus, hypothalamus or septum after chronic THC administration. In an attempt to replicate the GABA receptor binding changes and also to determine the [35S]TBPS binding in hippocampus, we designed Experiment 2. In this experiment, we dosed the animals by gavage with 0, 5, 10 or 20 mg THC/kg daily, 5 days/week or with 20 mg THC/kg Monday through Thursday and 60 mg/kg on Friday for 90 days. Results from this experiment failed to replicate the dose-dependent effect of THC on GABA receptor binding in hippocampus. Modulation of [35S]TBPS binding by GABA or 3 alpha-OH-DHP or inhibition by cold TBPS in frontal cortex did not show any significant dose-related effects

Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs.

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Larson, Jeanne C; Allstadt, Sara D; Fan, Timothy M; Khanna, Chand; Lunghofer, Paul J; Hansen, Ryan J; Gustafson, Daniel L; Legendre, Alfred M; Galyon, Gina D; LeBlanc, Amy K; Martin-Jimenez, Tomas

2016-01-01

To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. 5 healthy purpose-bred hounds. The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received rapamycin (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and noncompartmental analyses. Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in nanograms per milliliter. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, need to be determined.

Comparative pharmacokinetics of oxytetracycline in blunt-snout bream (Megalobrama amblycephala) with single and multiple-dose oral administration.

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Li, Ru-Qin; Ren, Yu-Wei; Li, Jing; Huang, Can; Shao, Jun-Hui; Chen, Xiao-Xuan; Wu, Zhi-Xin

2015-06-01

Research into the pharmacokinetics and residue elimination of oxytetracycline (OTC) is important both to determine the optimal dosage regimens and to establish a safe withdrawal time in fish. A depletion study is presented here for OTC in Megalobrama amblycephala with a single-dose (100 mg/kg) and multiple-dose (100 mg/kg for five consecutive days) oral administration. The study was conducted at 25 °C. As a result, a one-compartment model was developed. For the single dose, the absorption half-life was 5.79, 9.40, 6.96, and 8.06 h in the plasma, liver, kidney, and muscle, respectively. However, the absorption half-life was 3.62, 7.33, 4.59, and 6.02 h with multiple-dose oral administration. The elimination half-time in the plasma, liver, kidney, and muscle was 58.63, 126.43, 65.1, and 58.85 h when M. amblycephala was treated with a single dose. However, the elimination half-time changed to 91.75, 214.87, 126.22, and 135.84 h with multiple-dose oral administration.

Sequential gadolinium-enhanced magnetic resonance angiography of the aortoiliac and the femoropopliteal arteries with repetitive administration of low-dose contrast agent

International Nuclear Information System (INIS)

Ito, Koichiro; Kumazaki, Tatsuo

2000-01-01

To obtain a wide-range contrast MR angiography in a single examination, we performed two sequential administrations of low-dose (0.08 mmol/kg) gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) with three dimensional inversion recovery prepared fast spoiled gradient recalled acquisition in the steady-state (3D IR-fast SPGR) sequence. Signal characteristics of the sequence were estimated by computed simulations and an in vitro study. A clinical study of 19 examinations was done with sequential MR angiography of the aortoiliac and femoropopliteal arteries. Great signal differences were observed between the high and low Gd concentrations. Higher Gd concentrations generated significantly stronger signals. Greater signals were produced at TIs of longer than 150 msec than at shorter than 100 msec. In the clinical study, the arteries were visualized with sufficient signals even with a small amount of contrast agent. Contrast-to-noise ratios between the arteries and surrounding skeletal muscles or fat tissues ranged from 10.5±9.6 to 4.7±2.2 and 6.6±2.8 to -3.1±11.2, respectively. No venous enhancement was found with diluted contrast agent on the second MR angiography. Two consecutive contrast MR angiographies can be obtained with repetitive administration of low-dose contrast agent. (author)

Sequential gadolinium-enhanced magnetic resonance angiography of the aortoiliac and the femoropopliteal arteries with repetitive administration of low-dose contrast agent

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Ito, Koichiro [Nippon Medical School, Inba, Chiba (Japan). Chiba Hokusoh Hospital; Kumazaki, Tatsuo

2000-12-01

To obtain a wide-range contrast MR angiography in a single examination, we performed two sequential administrations of low-dose (0.08 mmol/kg) gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) with three dimensional inversion recovery prepared fast spoiled gradient recalled acquisition in the steady-state (3D IR-fast SPGR) sequence. Signal characteristics of the sequence were estimated by computed simulations and an in vitro study. A clinical study of 19 examinations was done with sequential MR angiography of the aortoiliac and femoropopliteal arteries. Great signal differences were observed between the high and low Gd concentrations. Higher Gd concentrations generated significantly stronger signals. Greater signals were produced at TIs of longer than 150 msec than at shorter than 100 msec. In the clinical study, the arteries were visualized with sufficient signals even with a small amount of contrast agent. Contrast-to-noise ratios between the arteries and surrounding skeletal muscles or fat tissues ranged from 10.5{+-}9.6 to 4.7{+-}2.2 and 6.6{+-}2.8 to -3.1{+-}11.2, respectively. No venous enhancement was found with diluted contrast agent on the second MR angiography. Two consecutive contrast MR angiographies can be obtained with repetitive administration of low-dose contrast agent. (author)

Stability and Concentration Verification of Ammonium Perchlorate Dosing Solutions

National Research Council Canada - National Science Library

Tsui, David

1998-01-01

Stability and concentration verification was performed for the ammonium perchlorate dosing solutions used in the on-going 90-Day Oral Toxicity Study conducted by Springborn Laboratories, Inc. (SLI Study No. 3433.1...

Intradermal Administration of Fractional Doses of Inactivated Poliovirus Vaccine: A Dose-Sparing Option for Polio Immunization.

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Okayasu, Hiromasa; Sein, Carolyn; Chang Blanc, Diana; Gonzalez, Alejandro Ramirez; Zehrung, Darin; Jarrahian, Courtney; Macklin, Grace; Sutter, Roland W

2017-07-01

A fractional dose of inactivated poliovirus vaccine (fIPV) administered by the intradermal route delivers one fifth of the full vaccine dose administered by the intramuscular route and offers a potential dose-sparing strategy to stretch the limited global IPV supply while further improving population immunity. Multiple studies have assessed immunogenicity of intradermal fIPV compared with the full intramuscular dose and demonstrated encouraging results. Novel intradermal devices, including intradermal adapters and disposable-syringe jet injectors, have also been developed and evaluated as alternatives to traditional Bacillus Calmette-Guérin needles and syringes for the administration of fIPV. Initial experience in India, Pakistan, and Sri Lanka suggests that it is operationally feasible to implement fIPV vaccination on a large scale. Given the available scientific data and operational feasibility shown in early-adopter countries, countries are encouraged to consider introducing a fIPV strategy into their routine immunization and supplementary immunization activities. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

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...... of pamidronate ranged from 0.01% to 0.35% of dose, with mean values of 0.11, 0.16, and 0.18% for 75, 150, and 300 mg, respectively. After i.v. infusion, the renal excretion of pamidronate was 26-53% of the dose, lower than for other bisphosphonates. The absolute bioavailability was 0.31% (range 0.08-0.7%) after...

Practical considerations in medical cannabis administration and dosing.

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MacCallum, Caroline A; Russo, Ethan B

2018-03-01

Cannabis has been employed medicinally throughout history, but its recent legal prohibition, biochemical complexity and variability, quality control issues, previous dearth of appropriately powered randomised controlled trials, and lack of pertinent education have conspired to leave clinicians in the dark as to how to advise patients pursuing such treatment. With the advent of pharmaceutical cannabis-based medicines (Sativex/nabiximols and Epidiolex), and liberalisation of access in certain nations, this ignorance of cannabis pharmacology and therapeutics has become untenable. In this article, the authors endeavour to present concise data on cannabis pharmacology related to tetrahydrocannabinol (THC), cannabidiol (CBD) et al., methods of administration (smoking, vaporisation, oral), and dosing recommendations. Adverse events of cannabis medicine pertain primarily to THC, whose total daily dose-equivalent should generally be limited to 30mg/day or less, preferably in conjunction with CBD, to avoid psychoactive sequelae and development of tolerance. CBD, in contrast to THC, is less potent, and may require much higher doses for its adjunctive benefits on pain, inflammation, and attenuation of THC-associated anxiety and tachycardia. Dose initiation should commence at modest levels, and titration of any cannabis preparation should be undertaken slowly over a period of as much as two weeks. Suggestions are offered on cannabis-drug interactions, patient monitoring, and standards of care, while special cases for cannabis therapeutics are addressed: epilepsy, cancer palliation and primary treatment, chronic pain, use in the elderly, Parkinson disease, paediatrics, with concomitant opioids, and in relation to driving and hazardous activities. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Protective Effect of Low Dose Gamma Irradiation against Oxidative Damage in Rats Administrated with Ferric- Nitrilotriacetate

International Nuclear Information System (INIS)

Mansonr, S.Z.

2009-01-01

Many studies have demonstrated the beneficial adaptive response of low dose gamma-irradiation. Low dose gamma-irradiation (LDR) might be effective for the prevention of various reactive oxygen species-related diseases. Ferric nitrilotriacetate (Fe-NTA) is a strong oxidant, which generates highly reactive hydroxyl radical and causes injuries of various organs including the kidney and liver. This study was designed to investigate the ability of low dose gamma-irradiation to restrain Fe-NT A induced oxidative stress. Sprague Dawley male albino rats were subjected to low dose gamma-irradiation (50 cGy). Animals were challenged with Fe-NT A (9 mg Fe/kg body weight, intraperitoneally). Results showed that Fe-NTA enhances lipid peroxidation (LPx) accompanied with reduction in glutathione (GSH) content, antioxidant enzymes, viz., glutathione peroxidase (GPX), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT) and phase-U metabolizing enzyme glutathione-S-transferase (GST). Fe-NTA also enhances the concentration of blood urea nitrogen (BUN) and serum creatinine as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) activities. Exposure to low dose gamma- irradiation (3 h after Fe-NTA administration) resulted in a significant decrease in LPx, BUN, serum creatinine contents as well as ALT, AST and GGT enzyme activities. GSH content; GST and antioxidant enzymes were also recovered to significant level. Thus, our data suggest that exposure to LDR might be a useful antioxidant mediator to suppress the Fe-NTA induced-oxidative damage in rats

Protective Effect of Low Dose Gamma Irradiation against Oxidative Damage in Rats Administrated with Ferric- Nitrilotriacetate

International Nuclear Information System (INIS)

Mansonr, S.Z.

2008-01-01

Many studies have demonstrated the beneficial adaptive response of low dose gamma-irradiation. Low dose gamma-irradiation (LDR) might be effective for the prevention of various reactive oxygen species-related diseases. Ferric nitrilotriacetate (Fe-NTA) is a strong oxidant, which generates highly reactive hydroxyl radical and causes injuries of various organs including the kidney and liver. This study was designed to investigate the ability of low dose gamma-irradiation to restrain Fe-NT A induced oxidative stress. Sprague Dawley male albino rats were subjected to low dose gamma-irradiation (50 cGy). Animals were challenged with Fe-NT A (9 mg Fe/kg body weight, intraperitoneally). Results showed that Fe-NTA enhances lipid peroxidation (LPx) accompanied with reduction in glutathione (GSH) content, antioxidant enzymes, viz., glutathione peroxidase (GPX), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT) and phase-U metabolizing enzyme glutathione-S-transferase (GST). Fe-NTA also enhances the concentration of blood urea nitrogen (BUN) and serum creatinine as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) activities. Exposure to low dose gamma- irradiation (3 h after Fe-NTA administration) resulted in a significant decrease in LPx, BUN, serum creatinine contents as well as ALT, AST and GGT enzyme activities. GSH content; GST and antioxidant enzymes were also recovered to significant level. Thus, our data suggest that exposure to LDR might be a useful antioxidant mediator to suppress the Fe-NTA induced-oxidative damage in rats

Calibrating passive sampling and passive dosing techniques to lipid based concentrations

DEFF Research Database (Denmark)

Mayer, Philipp; Schmidt, Stine Nørgaard; Annika, A.

2011-01-01

Equilibrium sampling into various formats of the silicone polydimethylsiloxane (PDMS) is increasingly used to measure the exposure of hydrophobic organic chemicals in environmental matrices, and passive dosing from silicone is increasingly used to control and maintain their exposure in laboratory...... coated vials and with Head Space Solid Phase Microextraction (HS-SPME) yielded lipid based concentrations that were in good agreement with each other, but about a factor of two higher than measured lipid-normalized concentrations in the organisms. Passive dosing was applied to bioconcentration...

Population pharmacokinetics of piperacillin in the early phase of septic shock: does standard dosing result in therapeutic plasma concentrations?

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Öbrink-Hansen, Kristina; Juul, Rasmus Vestergaard; Storgaard, Merete; Thomsen, Marianne Kragh; Hardlei, Tore Forsingdal; Brock, Birgitte; Kreilgaard, Mads; Gjedsted, Jakob

2015-11-01

Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic (PK) variability seen in this patient population. Piperacillin-tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. Accordingly, we determined the pharmacokinetic profile of piperacillin (4 g) every 8 h, during the third consecutive dosing interval, in 15 patients treated empirically for septic shock. We developed a population pharmacokinetic model to assess empirical dosing and to simulate alternative dosing regimens and modes of administration. Time above the MIC (T>MIC) predicted for each patient was evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter). Pharmacokinetic-pharmacodynamic (PK/PD) targets evaluated were 50% fT>4×MIC and 100% fT>MIC. A population PK model was developed using NONMEM, and data were best described by a two-compartment model. Central and intercompartmental clearances were 3.6 liters/h (relative standard error [RSE], 15.7%) and 6.58 liters/h (RSE, 16.4%), respectively, and central and peripheral volumes were 7.3 liters (RSE, 11.8%) and 3.9 liters (RSE, 9.7%), respectively. Piperacillin plasma concentrations varied considerably between patients and were associated with levels of plasma creatinine. Patients with impaired renal function were more likely to achieve predefined PK/PD targets than were patients with preserved or augmented renal function. Simulations of alternative dosing regimens showed that frequent intermittent bolus dosing as well as dosing by extended and continuous infusion increases the probability of attaining therapeutic plasma concentrations. For septic shock patients with preserved or augmented renal function, dose increment or prolonged infusion of the drug needs to be considered. (This study has been registered at ClinicalTrials.gov under registration no. NCT02306928.). Copyright © 2015, American Society for Microbiology

Inhibition of alloxan diabetes by low dose γ-irradiation before alloxan administration

International Nuclear Information System (INIS)

Yamaoka, Kiyonori; Takehara, Yoshiki; Yoshioka, Tamotsu; Utsumi, Kozo.

1994-01-01

We evaluated the inhibitory effects of whole body 60 Co-γ irradiation at a single low dose on alloxan-induced hyperglycemia in rats. (1) In rats that received alloxan, SOD activity in pancreas significantly decreased, but the decrease was inhibited by irradiation at a dose of 0.5 Gy. (2) Similarly, plasma peroxide, pancreatic peroxide, and blood glucose increased. However, the increase in pancreatic peroxide was inhibited by irradiation at a dose of 0.5 or 1.0 Gy and the increase in blood glucose by irradiation at 0.5 Gy. (3) After alloxan administration, degranulation was observed in cells, but this was inhibited by irradiation at 0.5 Gy. These results suggest that alloxan diabetes was inhibited by the increase of SOD activity in pancreas after low dose irradiation at 0.5 Gy. (author)

Pharmacokinetics of meloxicam following intravenous and oral administration in green iguanas (Iguana iguana).

Science.gov (United States)

Divers, Stephen J; Papich, Mark; McBride, Michael; Stedman, Nancy L; Perpinan, David; Koch, Thomas F; Hernandez, Sonia M; Barron, G Heather; Pethel, Melinda; Budsberg, Steven C

2010-11-01

To determine pharmacokinetics of meloxicam in healthy green iguanas following PO and IV administration and assess potential toxicity. 21 healthy green iguanas (Iguana iguana). To assess pharmacokinetics, 13 iguanas were administered a single dose (0.2 mg/kg) of meloxicam PO and, 14 days later, the same dose IV. To assess potential toxicity, 4 iguanas were given meloxicam at a dosage of 1 or 5 mg/kg, PO, every 24 hours for 12 days, and results of histologic examination were compared with results for another 4 iguanas given a single dose of meloxicam (0.2 mg/kg). There were no significant differences between PO and IV administration with regard to terminal half-life (mean ± SD, 12.96 ± 8.05 hours and 9.93 ± 4.92 hours, respectively), mean area under the curve to the last measured concentration (5.08 ± 1.62 μg•h/mL and 5.83 ± 2.49 μg•h/mL), volume of distribution (745 ± 475 mL/kg and 487 ± 266 mL/kg), or clearance (40.17 ± 10.35 mL/kg/h and 37.17 ± 16.08 mL/kg/h). Maximum plasma concentration was significantly greater following IV (0.63 ± 0.17 μg/mL) versus PO (0.19 ± 0.07 μg/mL) administration. Time from administration to maximum plasma concentration and mean residence time were significantly longer following PO versus IV administration. Daily administration of high doses (1 or 5 mg/kg) for 12 days did not induce any histologic changes in gastric, hepatic, or renal tissues. Results suggested that administration of meloxicam at a dose of 0.2 mg/kg IV or PO in green iguanas would result in plasma concentrations > 0.1 μg/mL for approximately 24 hours.

Absorbed dose estimates from a single measurement one to three days after the administration of 177Lu-DOTATATE/-TOC.

Science.gov (United States)

Hänscheid, Heribert; Lapa, Constantin; Buck, Andreas K; Lassmann, Michael; Werner, Rudolf A

2017-01-01

To retrospectively analyze the accuracy of absorbed dose estimates from a single measurement of the activity concentrations in tumors and relevant organs one to three days after the administration of 177 Lu-DOTA-TATE/TOC assuming tissue specific effective half-lives. Activity kinetics in 54 kidneys, 30 neuroendocrine tumor lesions, 25 livers, and 27 spleens were deduced from series of planar images in 29 patients. After adaptation of mono- or bi-exponential fit functions to the measured data, it was analyzed for each fit function how precise the time integral can be estimated from fixed tissue-specific half-lives and a single measurement at 24, 48, or 72 h after the administration. For the kidneys, assuming a fixed tissue-specific half-life of 50 h, the deviations of the estimate from the actual integral were median (5 % percentile, 95 % percentile): -3 °% (-15 %>; +16 °%) for measurements after 24 h, +2 %> (-9 %>; +12 %>) for measurements after 48 h, and 0 % (-2 %; +12 %) for measurements after 72 h. The corresponding values for the other tissues, assuming fixed tissue-specific half-lives of 67 h for liver and spleen and 77 h for tumors, were +2 % (-25 %; +20 %) for measurements after 24 h, +2 °% (-16 %>; +17 %>) for measurements after 48 h, and +2 %> (-11 %>; +10 %>) for measurements after 72 h. Especially for the kidneys, which often represent the dose limiting organ, but also for liver, spleen, and neuroendocrine tumors, a meaningful absorbed dose estimate is possible from a single measurement after 2, more preferably 3 days after the administration of 177 Lu-DOTA-TATE/-TOC assuming fixed tissue specific effective half-lives. Schattauer GmbH.

Neuroprotection of lamotrigine on hypoxic-ischemic brain damage in neonatal rats: Relations to administration time and doses

Directory of Open Access Journals (Sweden)

Yong-Hong Yi

2008-06-01

Full Text Available Yong-Hong Yi1, Wen-Chao Guo1, Wei-Wen Sun1, Tao Su1, Han Lin1, Sheng-Qiang Chen1, Wen-Yi Deng1, Wei Zhou2, Wei-Ping Liao11Department of Neurology, Institute of Neurosciences and the Second Affiliated Hospital, 2Department of Neonatology, Affiliated Guangzhou Children’s Hospital, Guangzhou Medical College, Guangzhou, Guangdong Province, P.R. ChinaAbstract: Lamotrigine (LTG, an antiepileptic drug, has been shown to be able to improve cerebral ischemic damage by limiting the presynaptic release of glutamate. The present study investigated further the neuroprotective effect of LTG on hypoxic-ischemic brain damage (HIBD in neonatal rats and its relations to administration time and doses. The HIBD model was produced in 7-days old SD rats by left common carotid artery ligation followed by 2 h hypoxic exposure (8% oxygen. LTG was administered intraperitoneally with the doses of 5, 10, 20, and 40 mg/kg 3 h after operation and the dose of 20 mg/kg 1 h before and 3 h, 6 h after operation. Blood and brain were sampled 24 h after operation. Nissl staining, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL, and neuron-specific enolase (NSE immunohistochemical staining were used for morphological studies. Water content in left cortex and NSE concentration in serum were determined. LTG significantly reduced water content in the cerebral cortex, as well as the number of TUNEL staining neurons in the dentate gyrus and cortex in hypoxic-ischemia (HI model. Furthermore, LTG significantly decreased the NSE level in serum and increased the number of NSE staining neurons in the cortex. These effects, except that on water content, were dose-dependent and were more remarkable in the pre-treated group than in the post-treated groups. These results demonstrate that LTG may have a neuroprotective effect on acute HIBD in neonates. The effect is more prominent when administrated with higher doses and before HI.Keywords: hypoxic-ischemic brain

Distribution of enrofloxacin in intestinal tissue and contents of healthy pigs after oral and intramuscular administrations

DEFF Research Database (Denmark)

Wiuff, C.; Lykkesfeldt, J.; Aarestrup, Frank Møller

2002-01-01

The concentration of enrofloxacin in plasma, intestinal tissue, lymph nodes and intestinal contents was investigated in healthy pigs after oral (p.o.) and intramuscular (i.m.) administration of a single dose of 2.5 mg/kg bw. Tissue and content samples were collected from jejunum, ileum, caecum...... administration, and maximum concentrations in tissue and plasma were determined later than after i.m. administration. No difference between route of administration was observed in the intestinal content. Enrofloxacin concentrations in faeces during a 5-day dosing regimen with i.m. and p.o. administration were....... On the basis of these results it was concluded that in order to ensure an immediate high concentration of enrofloxacin, and thereby avoid an initial selection for resistant mutants, the intramuscular route seems to be preferable to the oral route....

Effectiveness of increasing the frequency of posaconazole syrup administration to achieve optimal plasma concentrations in patients with haematological malignancy.

Science.gov (United States)

Park, Wan Beom; Cho, Joo-Youn; Park, Sang-In; Kim, Eun Jung; Yoon, Seonghae; Yoon, Seo Hyun; Lee, Jeong-Ok; Koh, Youngil; Song, Kyoung-Ho; Choe, Pyoeng Gyun; Yu, Kyung-Sang; Kim, Eu Suk; Bang, Su Mi; Kim, Nam Joong; Kim, Inho; Oh, Myoung-Don; Kim, Hong Bin; Song, Sang Hoon

2016-07-01

Few data are available on whether adjusting the dose of posaconazole syrup is effective in patients receiving anti-cancer chemotherapy. The aim of this prospective study was to analyse the impact of increasing the frequency of posaconazole administration on optimal plasma concentrations in adult patients with haematological malignancy. A total of 133 adult patients receiving chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome who received posaconazole syrup 200 mg three times daily for fungal prophylaxis were enrolled in this study. Drug trough levels were measured by liquid chromatography-tandem mass spectrometry. In 20.2% of patients (23/114) the steady-state concentration of posaconazole was suboptimal (increased to 200 mg four times daily. On Day 15, the median posaconazole concentration was significantly increased from 368 ng/mL [interquartile range (IQR), 247-403 ng/mL] to 548 ng/mL (IQR, 424-887 ng/mL) (P = 0.0003). The median increase in posaconazole concentration was 251 ng/mL (IQR, 93-517 ng/mL). Among the patients with initially suboptimal levels, 79% achieved the optimal level unless the steady-state level was increasing the administration frequency of posaconazole syrup is effective for achieving optimal levels in patients with haematological malignancy undergoing chemotherapy. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Inhibition of alloxan diabetes by low dose {gamma}-irradiation before alloxan administration

Energy Technology Data Exchange (ETDEWEB)

Yamaoka, Kiyonori [Central Research Inst. of Electric Power Industry, Komae, Tokyo (Japan). Komae Research Lab.; Takehara, Yoshiki; Yoshioka, Tamotsu; Utsumi, Kozo

1994-10-01

We evaluated the inhibitory effects of whole body {sup 60}Co-{gamma} irradiation at a single low dose on alloxan-induced hyperglycemia in rats. (1) In rats that received alloxan, SOD activity in pancreas significantly decreased, but the decrease was inhibited by irradiation at a dose of 0.5 Gy. (2) Similarly, plasma peroxide, pancreatic peroxide, and blood glucose increased. However, the increase in pancreatic peroxide was inhibited by irradiation at a dose of 0.5 or 1.0 Gy and the increase in blood glucose by irradiation at 0.5 Gy. (3) After alloxan administration, degranulation was observed in cells, but this was inhibited by irradiation at 0.5 Gy. These results suggest that alloxan diabetes was inhibited by the increase of SOD activity in pancreas after low dose irradiation at 0.5 Gy. (author).

Comparative pharmacokinetics of a fixed-dose combination vs concomitant administration of telmisartan and S-amlodipine in healthy adult volunteers.

Science.gov (United States)

Oh, Minkyung; Park, Sung-Eun; Ghim, Jong-Lyul; Choi, Young-Kyung; Shim, Eon-Jeong; Shin, Jae-Gook; Kim, Eun-Young

2017-01-01

This study compared the pharmacokinetic (PK) and safety profiles of a fixed-dose combination (FDC) formulation of telmisartan and S-amlodipine with those of concomitant administration of the two drugs. This was an open-label, randomized, crossover study in healthy male Koreans. All subjects were administered an FDC tablet containing 40 mg telmisartan and 5 mg S-amlodipine and were also coadministered the same dose of both drugs given separately. The crossover study design included a 14-day washout period between the two treatments. Blood samples were collected up to 168 h following drug administration. The plasma concentrations of telmisartan and S-amlodipine were determined by liquid chromatography tandem mass spectrometry. PK parameters and plasma concentration-time curves were compared. Safety was assessed by measuring vital signs, clinical laboratory tests, physical examinations, and patient interviews. The geometric mean ratios and 90% CIs for the maximum plasma concentration (C max ) and area under the curve from time zero to the last sampling time (AUC t ) were 0.8782 (0.8167-0.9444) and 0.9662 (0.9210-1.0136) for telmisartan and 1.0069 (0.9723-1.0427) and 1.0324 (0.9969-1.0690) for S-amlodipine, respectively. A total of 36 adverse events (AEs) were reported by 23 subjects, but no statistical differences were observed between the two treatments. The most frequently reported AE was a mild-to-moderate headache that was generally self-limiting. For both telmisartan and S-amlodipine, the C max and AUC t 90% CIs were between ln (0.8) and ln (1.25). These results suggest that the FDC formulation is pharmacokinetically bioequivalent and has a similar safety profile to the coadministration of these drugs.

Women Administered Standard Dose Imatinib for Chronic Myeloid Leukemia Have Higher Dose-Adjusted Plasma Imatinib and Norimatinib Concentrations Than Men.

Science.gov (United States)

Belsey, Sarah L; Ireland, Robin; Lang, Kathryn; Kizilors, Aytug; Ho, Aloysius; Mufti, Ghulam J; Bisquera, Alessandra; De Lavallade, Hugues; Flanagan, Robert J

2017-10-01

The standard dose of imatinib for the treatment of chronic-phase chronic myeloid leukemia (CML) is 400 mg·d. A predose plasma imatinib concentration of >1 mg·L is associated with improved clinical response. This study aimed to assess the plasma imatinib and norimatinib concentrations attained in patients with chronic myeloid leukemia administered standard doses of imatinib adjusted for dose, age, sex, body weight, and response. We evaluated data from a cohort of patients treated between 2008 and 2014 with respect to dose, age, sex, body weight, and response. The study comprised 438 samples from 93 patients (54 male, 39 female). The median imatinib dose was 400 mg·d in men and in women. The plasma imatinib concentration ranged 0.1-5.0 mg·L and was below 1 mg·L in 20% and 16% of samples from men and women, respectively. The mean dose normalized plasma imatinib and norimatinib concentrations were significantly higher in women in comparison with men. This was partially related to body weight. Mixed effects ordinal logistic regression showed no evidence of an association between sex and plasma imatinib (P = 0.13). However, there was evidence of an association between sex and plasma norimatinib, with higher norimatinib concentrations more likely in women than in men (P = 0.02). Imatinib therapeutic drug monitoring only provides information on dosage adequacy and on short-term adherence; longer-term adherence cannot be assessed. However, this analysis revealed that approximately 1 in 5 samples had a plasma imatinib concentration <1 mg·L, which was suggestive of inadequate dosage and/or poor adherence and posed a risk of treatment failure. Higher imatinib exposure in women may be a factor in the increased rate of long-term, stable, deep molecular response (undetectable breakpoint cluster-Abelson (BCR-ABL) transcript levels with a PCR sensitivity of 4.5 log, MR4.5) reported in women.

Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 4 h apart Human pharmacology of MDMA after repeated doses taken 4 h apart.

Science.gov (United States)

Farré, Magí; Tomillero, Angels; Pérez-Mañá, Clara; Yubero, Samanta; Papaseit, Esther; Roset, Pere-Nolasc; Pujadas, Mitona; Torrens, Marta; Camí, Jordi; de la Torre, Rafael

2015-10-01

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

The effects of variations in dose and method of administration on glucagon like peptide-2 activity in the rat

DEFF Research Database (Denmark)

Kaji, Tatsuru; Tanaka, Hiroaki; Holst, Jens Juul

2008-01-01

Glucagon-like peptide-2 (GLP-2) is a potent, intestinal-specific trophic hormone. However, the relationship between the dose and timing of GLP-2 administration and these trophic effects is not clear. We investigated the effects of variations in the dose and timing of GLP-2 administration on its...

Intrapulmonary concentration of enrofloxacin in healthy calves

Science.gov (United States)

OTOMARU, Konosuke; HIRATA, Masaya; IKEDO, Tomonobu; HORINOUCHI, Chie; NOGUCHI, Michiko; ISHIKAWA, Shingo; NAGATA, Shun-ichi; HOBO, Seiji

2015-01-01

To determine the intrapulmonary concentration of enrofloxacin (ERFX) in calves, plasma, bronchoalveolar lavage fluid (BALF) and alveolar cells samples were obtained from clinically healthy calves. Four clinically healthy calves were administered a single dose of ERFX (5 mg/kg) by subcutaneous injection. Samples of plasma were obtained for each subjects at 0 (before administration), 1 and 2 hr after administration of ERFX. Samples of BALF were obtained from each subject at 0, 1 and 2 hr after administration of ERFX. This examination was conducted two times, one week apart. The mean EFRX concentrations in plasma at 1 and 2 hr after administration were l.23 and 1.29 µg/ml, respectively. The mean EFRX concentrations in pulmonary epithelial lining fluid (ELF) at 1 and 2 hr after administration 8.53 µg/ml and 9.42 µg/ml, respectively. The mean ERFX concentrations of alveolar cells in BALF at 1 and 2 hr after administration were 4.04 µg/ml and 5.19 µg/ml, respectively. These results suggest that the ERFX concentrations in ELF and alveolar cells concentrations in BALF at 1 and 2 hr after administration were higher than the plasma concentrations. PMID:26668174

A sensitivity study on neutron flux variation due to 10B concentration in dose calculation for BNCT

International Nuclear Information System (INIS)

Jung, Sang Hoon

2006-02-01

The effects of inclusion of 10 B concentration on neutron flux and dose in dose calculation were studied. In order to provide the quantitative effects of inclusion of 10 B concentrations on depressions of neutron and photon flux and dose, the fluxes and doses with voxel head phantoms for various 10 B concentrations homogeneously distributed were calculated by using MCNPX simulations. A lithium target system and beam shaping assembly, which have been developed at the Hanyang University, were used as epithermal neutron beam. The calculation results show that the neutron flux at the center of the head phantom decreases by approximately 5.4% per 10 ppm of 10 B concentration in comparison with the neutron flux in the case of boron-free. It was also observed that the tissue dose at the center of the head phantom is depressed by approximately 4.7% per 10 ppm of the 10 B concentration and the tumor dose by approximately 5.3% per 10 ppm. According to depth of tumors, it was observed that the depressions of the doses in the tumors are ranged in 3.7 ∼ 9.2%. The dose calculations in the case of boron-free show that it is overestimated in comparison with the dose calculations in the cases of the inclusion of 10 B concentrations for the normal tissue and the tumors. Therefore, in dose calculation for BNCT, the depressions of neutron flux and dose should be considered. The results in this study are available to setting up the depression ratios which can be used for converting neutron and gamma fluxes and doses in phantom with boron free into the fluxes and doses in phantom with inclusion of 10 B concentrations in treatment. It is expected that the depression ratios is practicable to dose evaluation for BNCT

Evaluation of occupational radiation dose in nuclear medicine: radiopharmaceutical administration to scintiscanning exams of myocardial perfusion

International Nuclear Information System (INIS)

Komatsu, Cassio V.; Michelin, Charlie A.; Jakubiak, Rosangela R.; Lemes, Alyne O.; Silva, Juliana L.M.

2013-01-01

In nuclear medicine, workers directly involved in exams are constantly exposed to ionizing radiation. The procedure for administration of the radiopharmaceutical to the patient is one of the most critical times of exposure. In tests of myocardial perfusion scintigraphy (MPS) administration of radiopharmaceutical repeats the steps of rest and cardiac stress. In this study, we used a Geiger -Mueller detector for measuring occupational radiation doses for during the administration of technetium- 99m - sestamibi in MPS tests. In the evaluation, discriminated the stages of examination and related professional experience time to doses measures at home. It were followed 110 procedures at home (55 conducted by professionals with over 5 years experience and 55 conducted by professionals with less than 1 year of experience) and 55 effort procedures. The results showed that the rest of the procedure time and dose are related to the experience of the worker. More experienced workers were faster (mean: 43 ± 16 vs 67 ± 25 seconds / procedure), and therefore received lower doses (mean 0.57 ± 0.16 versus 0.80 ± 0.24 μSv / procedure), both with statistical significance (p <0.001). In step effort, there were procedures lasting longer (mean: 19 ± 2 minutes / procedure), which resulted in higher doses (mean 3.0 ± 0.6 μSv / procedure)

Final report of evaluation of dose and measurement of radon concentration

International Nuclear Information System (INIS)

1998-03-01

A mean annual exposure to radon daughters in indoor air was estimated on the basis of measurement of radon concentration in indoor air in Japan from fiscal 1992 to 1996. Doses were estimated by UNSCEAR method. The representative values in this report show the mean values in whole Japan. Each dose in the local area was different reflecting the different concentration of radon daughters. However, the same parameters were used in each area. When mean annual dose of radon daughters was estimated, we used 15.5 Bq m -3 mean annual exposure to radon daughters in indoor air, 5 Bq m -3 that in outdoor air, 0.4 the equilibrium factor indoor, 0.6 the equilibrium factor outdoor and 0.9 of P. The model of UNSCEAR based on these above values gave 0.46 mSv y -1 mean annual dose of radon daughters which were consisted of from 0.38 mSv y -1 in Kanto district to 0.52 mSv y -1 Kyushu, Okinawa district. (S.Y.)

Final report of evaluation of dose and measurement of radon concentration

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-03-01

A mean annual exposure to radon daughters in indoor air was estimated on the basis of measurement of radon concentration in indoor air in Japan from fiscal 1992 to 1996. Doses were estimated by UNSCEAR method. The representative values in this report show the mean values in whole Japan. Each dose in the local area was different reflecting the different concentration of radon daughters. However, the same parameters were used in each area. When mean annual dose of radon daughters was estimated, we used 15.5 Bq m{sup -3} mean annual exposure to radon daughters in indoor air, 5 Bq m{sup -3} that in outdoor air, 0.4 the equilibrium factor indoor, 0.6 the equilibrium factor outdoor and 0.9 of P. The model of UNSCEAR based on these above values gave 0.46 mSv y{sup -1} mean annual dose of radon daughters which were consisted of from 0.38 mSv y{sup -1} in Kanto district to 0.52 mSv y{sup -1} Kyushu, Okinawa district. (S.Y.)

Effect of dose on lead retention and distribution in suckling and adult female mice

International Nuclear Information System (INIS)

Keller, C.A.; Doherty, R.A.

1980-01-01

Single doses of lead (trace to 445 mg/kg) were administered per os to suckling and adult mice. Both groups exhibited dose-independent lead retention when doses of 4 to 445 mg/kg were administered. However, developmental differences in the fraction of initial dose (FID) retained were evident for all doses administered. A much larger FID was retained in both age groups following administration of carrier-free 203 Pb. The results are consistent with a mechanism of gastrointestinal lead absorption comprising two or more processes. Developmental differences were also observed in organ lead concentration relative to whole body concentration for kidneys, skull and brain 6 days following lead administration. Lead retentions (relative to whole body retention) in brain and in bone were linearly related to dose of lead administered in both suckling and adult age groups. Though uptake of lead into brain and into femur was observed to be directly related to dose over a wide range, relative blood lead concentrations were not linearly correlated with dose administered. The relationships between lead concentrations of blood and organ(s) were also shown to be nonlinear relative to dose. However, blood lead concentration was found to be a reliable indicator of kidney and liver lead concentrations following an acute lead exposure

Lung concentrations of telithromycin after oral dosing.

Science.gov (United States)

Khair, O A; Andrews, J M; Honeybourne, D; Jevons, G; Vacheron, F; Wise, R

2001-06-01

Concentrations of telithromycin were measured in plasma, bronchial mucosa (BM), epithelial lining fluid (ELF) and alveolar macrophages (AM) following multiple oral doses. Concentrations were determined using a microbiological assay. There were 20 subjects in the study, allocated to three nominal time periods: 2, 12 and 24 h. Mean concentrations in plasma, BM, ELF and AM for 2, 12 and 24 h were as follows: 2 h, 1.86 mg/L, 3.88 mg/kg, 14.89 mg/L and 69.32 mg/L; 12 h, 0.23 mg/L, 1.41 mg/kg, 3.27 mg/L and 318.1 mg/L; and 24 h, 0.08 mg/L, 0.78 mg/kg, 0.97 mg/L and 161.57 mg/L. These concentrations of telithromycin in BM and ELF exceeded for 24 h the mean MIC90s of the common respiratory pathogens Streptococcus pneumoniae (0.12 mg/L) and Moraxella catarrhalis (0.03 mg/L), as well as the atypical microorganism Mycoplasma pneumoniae (0.001 mg/L), and suggest that telithromycin may be effective for the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.

Andrographis paniculata: Dissolution investigation and pharmacokinetic studies of four major active diterpenoids after multiple oral dose administration in healthy Thai volunteers.

Science.gov (United States)

Pholphana, Nanthanit; Panomvana, Duangchit; Rangkadilok, Nuchanart; Suriyo, Tawit; Puranajoti, Porranee; Ungtrakul, Teerapat; Pongpun, Wanwisa; Thaeopattha, Saichit; Songvut, Phanit; Satayavivad, Jutamaad

2016-12-24

Andrographis paniculata is included in 'The National List of Essential Herbal Drugs A.D. 1999' of Thailand as an herbal drug for the treatment of common cold symptoms and non-infectious diarrhea. The therapeutic activities of A. paniculata are attributed to four major active diterpenoids: andrographolide (1), 14-deoxy-11, 12-didehydroandrographolide (2), neoandrographolide (3), and 14-deoxyandrographolide (4). However, the pharmacokinetic studies in humans of this plant were performed after a single oral dose administration and reported the parameters related to be of only 1. This study aims to determine the pharmacokinetic parameters of four major active diterpenoids after multiple oral dose administration of A. paniculata capsules in healthy volunteers. The dissolution testing of these four diterpenoids was also performed. The dissolution testing of four major active diterpenoids was conducted in pH 1.2, pH 4.5, and pH 6.8 for 10-100min. The pharmacokinetic study of these active diterpenoids was designed as an open-label, multiple oral dose administration of A. paniculata capsules in 20 healthy Thai volunteers at 1:1 ratio of female and male. Each volunteer was given four A. paniculata capsules each time which contained 1, 2, 3, and 4 in the quantities of 32.64, 5.40, 3.60, and 3.84mg, respectively, three times a day for three consecutive days. On the fourth day, after the first dose of the day was administered, blood samples were collected at the predefined time points. The validated LC-MS/MS method was used to simultaneously determine the concentrations of these diterpenoids in the human plasma samples. The pharmacokinetic parameters of each active diterpenoid were determined. All four major active diterpenoids have been completely dissolved in the simulated pH of gastrointestinal tract within 60min of dissolution. The dissolution profiles were found to be highest in pH 6.8 and lowest in pH 1.2, especially for 3. In the pharmacokinetic study, although 1 was

Problems in radiation absorbed dose estimation from positron emitters

International Nuclear Information System (INIS)

Powell, G.F.; Harper, P.V.; Reft, C.S.; Chen, C.T.; Lathrop, K.A.

1986-01-01

The positron emitters commonly used in clinical imaging studies for the most part are short-lived, so that when they are distributed in the body the radiation absorbed dose is low even though most of the energy absorbed is from the positrons themselves rather than the annihilation radiation. These considerations do not apply to the administration pathway for a radiopharmaceutical where the activity may be highly concentrated for a brief period rather than distributed in the body. Thus, high local radiation absorbed doses to the vein for an intravenous administration and to the upper airways during administration by inhalation can be expected. For these geometries, beta point source functions (FPS's) have been employed to estimate the radiation absorbed dose in the present study. Physiologic measurements were done to determine other exposure parameters for intravenous administration of O-15 and Rb-82 and for administration of O-15-CO 2 by continuous breathing. Using FPS's to calculate dose rates to the vein wall from O-15 and Rb-82 injected into a vein having an internal radius of 1.5 mm yielded dose rates of 0.51 and 0.46 (rad x g/μCi x h), respectively. The dose gradient in the vein wall and surrounding tissues was also determined using FPS's. Administration of O-15-CO 2 by continuous breathing was also investigated. Using ultra-thin thermoluninescent dosimeters (TLD's) having the effective thickness of normal tracheal mucosa, experiments were performed in which 6 dosimeters were exposed to known concentrations of O-15 positrons in a hemicylindrical tracheal phantom having an internal radius of 0.96 cm and an effective length of 14 cm. The dose rate for these conditions was 3.4 (rads/h)/(μCi/cm 3 ). 15 references, 7 figures, 6 tables

Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs: A pilot study

Science.gov (United States)

Larson, Jeanne C.; Allstadt, Sara D.; Fan, Timothy M.; Khanna, Chand; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Legendre, Alfred M.; Galyon, Gina D.; LeBlanc, Amy K.; Martin-Jimenez, Tomas

2017-01-01

Objective To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. Animals 5 healthy purpose-bred hounds. Procedures The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and non-compartmental analyses. Results Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Conclusions and Clinical Relevance Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in ng/mL. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, needs to be determined. PMID:26709938

The effects of low and moderate doses of caffeine supplementation on upper and lower body maximal voluntary concentric and eccentric muscle force.

Science.gov (United States)

Tallis, Jason; Yavuz, Harley C M

2018-03-01

Despite the growing quantity of literature exploring the effect of caffeine on muscular strength, there is a dearth of data that directly explores differences in erogenicity between upper and lower body musculature and the dose-response effect. The present study sought to investigate the effects of low and moderate doses of caffeine on the maximal voluntary strength of the elbow flexors and knee extensors. Ten nonspecifically strength-trained, recreationally active participants (aged 21 ± 0.3 years) completed the study. Using a randomised, counterbalanced, and double-blind approach, isokinetic concentric and eccentric strength was measured at 60 and 180°/s following administration of a placebo, 3 mg·kg -1 body mass caffeine, and 6 mg·kg -1 body mass caffeine. There was no effect of caffeine on the maximal voluntary concentric and eccentric strength of the elbow flexors, or the eccentric strength of the knee extensors. Both 3 and 6 mg·kg -1 body mass caffeine caused a significant increase in peak concentric force of the knee extensors at 180°/s. No difference was apparent between the 2 concentrations. Only 6 mg·kg -1 body mass caused an increase in peak concentric force during repeated contractions. The results infer that the effective caffeine concentration to evoke improved muscle performance may be related to muscle mass and contraction type. The present work indicates that a relatively low dose of caffeine treatment may be effective for improving lower body muscular strength, but may have little benefit for the strength of major muscular groups of the upper body.

Age and body composition influence TSH concentrations after administration of rhTSH.

Science.gov (United States)

Holthausen, F F; von Müller, F; Happel, C; Kranert, W T; Grünwald, F

2015-01-01

Previous studies listed body surface area (BSA), lean body mass (LBM), and age as modifying factors on the TSH concentrations after administration of recombinant human thyrotropin (rhTSH). The purpose of this study was to identify the main modifying factors on serum TSH levels and to compare the stimulation via single rhTSH injection after a short thyroid hormone withdrawal (THW) with that of the standard stimulating protocol. 106 patients with differentiated thyroid cancer (DTC) undergoing radioiodine therapy (RIT) after rhTSH administration were obtained through chart review. Two groups were evaluated: Group I was treated with a single rhTSH administration after two weeks of T3 therapy followed by one week of THW. Group II was stimulated according to the international standard protocol via rhTSH injections for two consecutive days. Serum TSH concentrations were documented prior to rhTSH administration (day 1 TSH), one day after (day 3 TSH) and 3-6 days after (mean 4.2 days, day 6 TSH) the last rhTSH injection. The following data was collected: age, gender, weight, height, BMI, LBM, BSA, residual thyroid tissue, CRP, creatinine, GFR, liver enzymes, alkaline phosphatase, cholesterol, and triglycerides. Group I: Age combined with anthropometric factors like BMI (TSH increase and day 6 TSH), BSA (TSH decrease), and gender (day 6 TSH) are the main modifying factors on serum TSH concentrations after rhTSH administration. Group II: Age and lean body mass (LBM) showed a significant impact on day 3 TSH, TSH increase (day 3-day 1), and TSH decrease (day 6-day 3). Day 6 TSH was found to be influenced by GFR (group II). Age and anthropometric parameters have significant independent influence on TSH concentrations after rhTSH injection in both groups. Anthropometric parameters (BSA, LBM) and demographic parameters (female gender) show strong influence on TSH concentrations. Further research should be conducted to examine the influence of body compartments on TSH levels

Calcium alpha-ketoglutarate administration to malnourished hemodialysis patients improves plasma arginine concentrations.

Science.gov (United States)

Riedel, E; Hampl, H; Steudle, V; Nündel, M

1996-01-01

Calcium alpha-ketoglutarate administration to 24 malnourished hemodialysis patients for 1 year leads to a significant increase in plasma concentrations of L-arginine from 53.6 +/- 18.3 (compared to a healthy control group: 87.5 +/- 27.3) to 71.1 +/- 15.9 mumol/l (p calcium alpha-ketoglutarate administration.

Preparation of 0.05% FK506 suspension eyedrops and its pharmacokinetics after topical ocular administration.

Science.gov (United States)

Yuan, Jin; Zhai, Jia-jie; Chen, Jia-qi; Ye, Cheng-tian; Zhou, Shi-you

2009-08-01

To investigate the stability of FK506 eye suspension and its pharmacokinetics in rabbit aqueous humor, as well as its distribution in eye tissues. Sedimentation rate, flocculation value, redispersion time, rheological study, and accelerated experiment were determined for evaluating the stability of FK506 suspension. In a single-dose pharmacokinetic study, six rabbits were instilled a 25-microL drop of 0.05% FK506 suspension and aqueous humor samples were collected at different intervals after administration. In a multiple-dose pharmacokinetic study, a 25-microL drop of FK506 suspension was instilled into the right eye of six rabbits four times a day for 7 days. On the eighth day, aqueous humor samples were collected before the administration of the first, second, third dose, and at different checkpoints after the third dose. For tissue distribution study, six eyes per time points (18 rabbits in total) were treated with single dose of FK506 suspension, and the eyes were enucleated at 60, 100, and 240 min after treatment, then eye tissues were collected. The concentrations of FK506 in all samples were determined by LC-MS/MS. The preliminary results indicated that the stability of FK506 suspension was in accord with the standards of Chinese pharmacopoeia. The maximum concentrations of aqueous humor after single dose and multiple dose administrations were 31.40 +/- 9.32 ng/mL and 37.73 +/- 11.25 ng/mL, respectively. The concentration of FK506 in cornea at 60, 100, and 240 min after a single dose were 402.0 +/- 96.8 ng/g, 363.8 +/- 84.5 ng/g, and 220 +/- 62.3 ng/g, respectively. Determination of pharmacokinetic parameters of single-dose and multiple-dose administration, as well as the FK506 concentrations in eye tissues, showed that the FK506 formulation and the dosing regimen ensured the therapeutic concentration of FK506 for treating corneal allograft rejection. Based on the stability, single-dose and multiple-dose pharmacokinetics, and tissue distribution, FK506

Pharmacokinetics of subcutaneous versus intramuscular administration of ceftiofur crystalline-free acid to bearded dragons (Pogona vitticeps).

Science.gov (United States)

Churgin, Sarah M; Musgrave, Kari E; Cox, Sherry K; Sladky, Kurt K

2014-05-01

To compare pharmacokinetics after a single IM or SC injection of ceftiofur crystalline-free acid (CCFA) to bearded dragons (Pogona vitticeps). 8 adult male bearded dragons. In a preliminary experiment, doses of 15 and 30 mg/kg, SC, were compared in 2 animals, and 30 mg/kg resulted in a more desirable pharmacokinetic profile. Then, in a randomized, complete crossover experimental design, each bearded dragon (n = 6) received a single dose of 30 mg of CCFA/kg IM or SC; the experiment was repeated after a 28-day washout period with the other route of administration. Blood samples were collected at 10 time points for 288 hours after injection. Plasma concentrations of ceftiofur and desfuroylceftiofur metabolites were measured via reverse-phase high-performance liquid chromatography. Data were analyzed with a noncompartmental model. No adverse effects were observed. Plasma concentrations greater than a target minimum inhibitory concentration of 1 μg/mL were achieved by 4 hours after administration by both routes. Mean plasma concentrations remained > 1 μg/mL for > 288 hours for both routes of administration. A single dose of CCFA (30 mg/kg) administered IM or SC to bearded dragons yielded plasma concentrations of ceftiofur and its metabolites > 1 μg/mL for > 288 hours. The SC route would be preferred because of less variability in plasma concentrations and greater ease of administration than the IM route. Future studies should include efficacy data as well as evaluation of the administration of multiple doses.

Oral dosing by voluntary  administration of jellybeans. Refinement and reduction of variability

DEFF Research Database (Denmark)

Pakula, Malgorzata Maria; Dagnæs-Hansen, Frederik

2016-01-01

Administration of substances by oral gavage is a common procedure in biomedical research involving laboratory animals, however although highly efficient, the procedure includes fixation of the animals and is technically challenging. Oral gavage is a precise way to dose animals, however it may ind...

Radon and radium concentrations in bottled waters: An estimate of ingestion doses

International Nuclear Information System (INIS)

Duenas, C.; Fernandez, M.C.; Carretero, J.; Liger, E.

1997-01-01

Concentration levels of Ra-226 and Rn-222 have been analysed in most of the bottled waters commercially available in Spain. Concentrations up to about 600 Bq/m 3 with a geometric mean of 12 Bq/m 3 were observed for Ra-226. For Rn-222 a geometric mean of 1200 Bq/m 3 with values ranging from 52000 to 1400 Bq/m 3 were measured. Doses resulting from the consumption of these waters were calculated. The effective dose equivalents due to the intake of Ra-226 present in these waters are expected to range from about 102 to 2 μSv·y -1 . Dose equivalents to the stomach due to Rn-222 intake through water consumption are estimated to reach values around 30 μSv·y -1 . (author)

Histology and Gadolinium Distribution in the Rodent Brain After the Administration of Cumulative High Doses of Linear and Macrocyclic Gadolinium-Based Contrast Agents.

Science.gov (United States)

Lohrke, Jessica; Frisk, Anna-Lena; Frenzel, Thomas; Schöckel, Laura; Rosenbruch, Martin; Jost, Gregor; Lenhard, Diana Constanze; Sieber, Martin A; Nischwitz, Volker; Küppers, Astrid; Pietsch, Hubertus

2017-06-01

Retrospective studies in patients with primary brain tumors or other central nervous system pathologies as well as postmortem studies have suggested that gadolinium (Gd) deposition occurs in the dentate nucleus (DN) and globus pallidus (GP) after multiple administrations of primarily linear Gd-based contrast agents (GBCAs). However, this deposition has not been associated with any adverse effects or histopathological alterations. The aim of this preclinical study was to systematically examine differences between linear and macrocyclic GBCAs in their potential to induce changes in brain and skin histology including Gd distribution in high spatial resolution. Fifty male Wistar-Han rats were randomly allocated into control (saline, n = 10 rats) and 4 GBCA groups (linear GBCAs: gadodiamide and gadopentetate dimeglumine, macrocyclic GBCAs: gadobutrol and gadoteridol; n = 10 rats per group). The animals received 20 daily intravenous injections at a dose of 2.5 mmol Gd/kg body weight. Eight weeks after the last GBCA administration, the animals were killed, and the brain and skin samples were histopathologically assessed (hematoxylin and eosin; cresyl violet [Nissl]) and by immunohistochemistry. The Gd concentration in the skin, bone, brain, and skeletal muscle samples were analyzed using inductively coupled plasma mass spectroscopy (ICP-MS, n = 4). The spatial Gd distribution in the brain and skin samples was analyzed in cryosections using laser ablation coupled with ICP-MS (LA-ICP-MS, n = 3). For the ultra-high resolution of Gd distribution, brain sections of rats injected with gadodiamide or saline (n = 1) were assessed by scanning electron microscopy coupled to energy dispersive x-ray spectroscopy and transmission electron microscopy, respectively. No histological changes were observed in the brain. In contrast, 4 of 10 animals in the gadodiamide group but none of the animals in other groups showed macroscopic and histological nephrogenic systemic fibrosis-like skin

Enhanced bioavailability of opiates after intratracheal administration

International Nuclear Information System (INIS)

Findlay, J.W.A.; Jones, E.C.; McNulty, M.J.

1986-01-01

Several opiate analgesics have low oral bioavailabilities in the dog because of presystemic metabolism. Intratracheal administration may circumvent this first-pass effect. Three anesthetized beagles received 5-mg/kg doses of codeine phosphate intratracheally (i.t.), orally (p.o.) and intravenously (i.v.) in a crossover study. The following drugs were also studied in similar experiments: ethylmorphine hydrochloride (5 mg/kg), pholcodine bitartrate (10 mg/kg, hydrocodone bitartrate (4 mg/kg) and morphine sulfate (2.5 mg/kg). Plasma drug concentrations over the 24- to 48-hr periods after drug administrations were determined by radioimmunoassays. I.t. bioavailabilities [codeine (84%), ethylmorphine (100%), and morphine (87%)] of drugs with poor oral availabilities were all markedly higher than the corresponding oral values (14, 26, and 23%, respectively). I.t. bioavailabilities of pholcodine (93%) and hydrocodone (92%), which have good oral availabilities (74 and 79%, respectively), were also enhanced. In all cases, peak plasma concentrations occurred more rapidly after i.t. (0.08-0.17 hr) than after oral (0.5-2 hr) dosing and i.t. disposition often resembled i.v. kinetics. I.t. administration may be a valuable alternative dosing route, providing rapid onset of pharmacological activity for potent drugs with poor oral bioavailability

Minimising activity and dose with enhanced image quality by radiopharmaceutical administrations

International Nuclear Information System (INIS)

Hoeschen, C.; Mattsson, S.; Cantone, M. C.; Mikuz, M.; Lacasta, C.; Ebel, G.; Clinthorne, N.; Giussani, A.

2010-01-01

Owing to the introduction of new diagnostic procedures, such as computed tomography (CT), positron emission tomography (PET) and single photon emission computed tomography (SPECT), the individual dose caused by medical exposures has grown rapidly in the last years. This is especially a subject to radiation protection for nuclear medical diagnosis, since in this case radiopharmaceuticals are administered to the patient, meaning not only a radiation exposure to the diseased tissue but also to the healthy tissues of large parts of the body. 'Minimizing Activity and Dose with Enhanced Image quality by Radiopharmaceutical Administrations' (MADEIRA) is a project co-funded by the European Commission within the Seventh Euratom Framework Programme that aims to improve three-dimensional (3D) nuclear medical imaging technologies significantly. MADEIRA is aiming to improve the efficacy and safety of 3D PET and SPECT functional imaging by optimising the spatial resolution and the signal-to-noise ratio, improving the knowledge of the temporal variation of the radiopharmaceuticals' uptake in and clearance from tumorous and healthy tissues, and evaluation of the corresponding patient dose. Using an optimised imaging procedure that improves the information gained per unit administered dose, MADEIRA aims especially to reduce the dose to healthy tissues of the patient. In this paper, an overall summary of the current achievements will be presented. (authors)

Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration.

Science.gov (United States)

Berkó, Szilvia; Szűcs, Kálmán F; Balázs, Boglárka; Csányi, Erzsébet; Varju, Gábor; Sztojkov-Ivanov, Anita; Budai-Szűcs, Mária; Bóta, Judit; Gáspár, Róbert

2016-01-01

Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats. The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. Both intravenously and EP-administered neostigmine (0.2-66.7 μg/kg) increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 μg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes. The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice.

Efficacy of Single-dose and 2-dose Intravenous Administration of Ramosetron in Preventing Postoperative Nausea and Vomiting After Laparoscopic Gynecologic Operation: A Randomized, Double-blind, Placebo-controlled, Phase 2 Trial.

Science.gov (United States)

Lee, Banghyun; Kim, Kidong; Suh, Dong Hoon; Shin, Hyun-Jung; No, Jae Hong; Lee, Jung Ryeol; Jee, Byung Chul; Hwang, Jung Won; Do, Sang Hwan; Kim, Yong Beom

2017-06-01

This randomized trial investigated whether a 2-dose administration of intravenous ramosetron (5-hydroxytryptamine type 3 receptor antagonist) is more effective than a single-dose administration in preventing postoperative nausea and vomiting (PONV) in 89 patients who were scheduled to undergo laparoscopic operation for benign gynecologic diseases and to receive intravenous patient-controlled analgesia for relief of postoperative pain. After assignment at a ratio of 1:1, intravenous ramosetron (0.3 mg) was initially administered at the end of skin closure in all patients. Thereafter, ramosetron (0.3 mg) and placebo were administered to the study and control groups, respectively, at 4 hours after the operation. The baseline and operative characteristics were similar between the groups. The incidence of PONV during the 24-hour period after operation which was assessed as the primary endpoint did not differ between the groups. No serious adverse events occurred in either group. A 2-dose administration of intravenous ramosetron may not be superior to a single-dose administration in preventing PONV in patients undergoing laparoscopic operation for benign gynecologic diseases.

Povidone-Iodine Concentration and Dosing in Cataract Surgery.

Science.gov (United States)

Koerner, Jagger C; George, Mary J; Meyer, Dale R; Rosco, Michael G; Habib, Matthew M

2018-05-17

Iodine has been recognized as an effective bactericide since the 1800's, and povidone-iodine (PI) solution has been applied to the ocular surface and periocular skin since the 1980's to prevent endophthalmitis in cataract surgery. In vitro, PI solution kills bacteria very quickly at dilute concentrations (0.05-1.0%). In many instances, PI kills bacteria more quickly at these dilute concentrations than more conventional (5%-10%) concentrations. This is due to greater availability of diatomic free iodine in dilute solution, the bactericidal component of PI. The toxicity of PI, both in vitro and clinically has been shown to be related to concentration. Current American Academy of Ophthalmology (AAO) and the European Society of Cataract and Refractive Surgeons (ESCRS) recommendations regarding PI use suggest using 5% PI prior to surgery. An alternative dosing strategy uses dilute PI repetitively throughout cataract surgery (0.25% every thirty seconds). We review the povidone-iodine literature with attention to basic science and use of dilute PI. Copyright © 2018 Elsevier Inc. All rights reserved.

High concentrations of thiosulfate in scala tympani perilymph after systemic administration in the guinea pig.

Science.gov (United States)

Pierre, Pernilla Videhult; Engmér, Cecilia; Wallin, Inger; Laurell, Göran; Ehrsson, Hans

2009-02-01

High concentrations of the antioxidant thiosulfate reach scala tympani perilymph after i.v. administration in the guinea pig. Thiosulfate concentrations in perilymph remain elevated longer than in blood. This warrants further studies on the possibility of obtaining otoprotection by thiosulfate administration several hours before that of cisplatin without compromising the anticancer effect caused by cisplatin inactivation in the blood compartment. Thiosulfate may reduce cisplatin-induced ototoxicity, presumably by oxidative stress relief and formation of inactivate platinum complexes. This study aimed to explore to what extent thiosulfate reaches scala tympani perilymph after systemic administration in the guinea pig. Scala tympani perilymph (1 microl) was aspirated from the basal turn of each cochlea up to 3 h after thiosulfate administration (103 mg/kg b.w., i.v.). Blood samples were also taken. Thiosulfate was quantified by HPLC and fluorescence detection. Substantial thiosulfate concentrations were found in perilymph. The area under the concentration-time curve for thiosulfate in perilymph and blood was 3100 microMxmin and 6300 microMxmin, respectively. The highest thiosulfate concentrations in perilymph were found at the first sampling at about 10 min. Due to a more rapid elimination from blood, perilymph concentrations exceeded those of blood towards the end of the experiment.

Comparison of the deviation distribution in the doses administrated with and without mask in radiotherapeutic procedures

International Nuclear Information System (INIS)

Santos Junior, S. dos; Ghilardi N, T.

1998-01-01

In order to guarantee that the error limit in the dose administration is inside of the recommended limit by the ICRU (the ICRU recommends that the doses administrated in radiotherapy must be inside of a total deviation ± 5 %), the radiotherapy services are maintaining quality control programs and dosimetry which guarantee that the equipment yield or source should be known with precision. The Quality Control Programs foresee moreover the radiation beam calibration dosimetry, the In vivo dosimetry for obtaining a greater control of the administered doses. At present it counts on greater devices for maintaining the deviations inside this margin, and one of them is the u se of masks. The present work was carried out on a Siemens equipment model Gammatron S-80 (Co-60) in the Radiotherapy Service of the Sao Paulo University Hospital where teletherapy procedures are realized. (Author)

Single Oral Dose Toxicity Test of Blue Honeysuckle Concentrate in Mice

Science.gov (United States)

Park, Sang-In; Choi, Seung-Hoon; Song, Chang-Hyun; Park, Soo-Jin; Shin, Yong-Kook; Han, Chang-Hyun; Lee, Young Joon; Ku, Sae-Kwang

2015-01-01

The objective of this study was to obtain single oral dose toxicity information for concentrated and lyophilized powder of blue honeysuckle (Lonicera caerulea L., Caprifoliaceae; BHcL) in female and male ICR mice to aid in the process of developing natural origin medicinal ingredients or foods following proximate analysis and phytochemical profile measurement. The proximate analysis revealed that BHcL had an energy value of 3.80 kcal/g and contained 0.93 g/g of carbohydrate, 0.41 g/g of sugar, 0.02 g/g of protein, and 0.20 mg/g of sodium. BHcL did not contain lipids, including saturated lipids, trans fats, or cholesterols. Further, BHcL contained 4.54% of betaine, 210.63 mg/g of total phenols, 159.30 mg/g of total flavonoids, and 133.57 mg/g of total anthocyanins. Following administration of a single oral BHcL treatment, there were no treatment-related mortalities, changes in body weight (bw) or organ weight, clinical signs, necropsy or histopathological findings up to 2,000 mg/kg bw, the limited dosage for rodents of both sexes. We concluded that BHcL is a practically non-toxic material in toxicity potency. PMID:25874034

Dose-dependent effect of 8-day cisplatin administration upon the morphology of the albino guinea pig cochlea

NARCIS (Netherlands)

Cardinaal, RM; de Groot, JCMJ; Huizing, EH; Veldman, JE; Smoorenburg, GF

Numerous studies investigating cisplatin ototoxicity in animals have been performed, but it is difficult to derive a clear dose-effect relation from these studies. The degree of cisplatin-induced ototoxicity depends on a multitude of,factors. Many parameters, such as dose, mode of administration,

Concentrations of amoxicillin and clindamycin in teeth following a single dose of oral medication.

Science.gov (United States)

Schüssl, Yvonne; Pelz, Klaus; Kempf, Jürgen; Otten, Jörg-Elard

2014-01-01

The main purpose of this study is the detection of amoxicillin and clindamycin concentrations in teeth. Eleven patients received 2 g of amoxicillin, and 11 patients received 600 mg of clindamycin in a single dose of oral medication at least 60 min prior to tooth extraction due to systemic diseases. The concentrations were determined in crowns and roots separately using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Amoxicillin (13 samples) and clindamycin (12 samples) were detected in the samples of the root and crown preparations of the extracted teeth. The mean concentration of amoxicillin was 0.502 μg/g in the roots and 0.171 μg/g in the crowns. The mean concentration of clindamycin was 0.270 μg/g in the roots and 0.064 μg/g in the crowns. A single dose of oral amoxicillin and clindamycin leads to concentrations of both antibiotics in teeth which exceed the minimal inhibition concentration of some oral bacteria. The proof of antibacterial activity in dental hard tissue after oral single-dose application is new. The antimicrobial effect of amoxicillin and clindamycin concentrations in roots of teeth may be of clinical relevance to bacterial reinfection from dentinal tubules.

Serum thyroxine concentrations after radioactive iodine therapy in cats with hyperthyroidism

International Nuclear Information System (INIS)

Meric, S.M.; Hawkins, E.C.; Washabau, R.J.; Turrel, J.M.; Feldman, E.C.

1986-01-01

Thirty-one cats with hyperthyroidism were given one dose of radioactive iodine (131I) IV. Serum thyroxine (T4) concentrations were measured before treatment in all cats, at 12-hour intervals after treatment in 10 cats, and at 48-hour intervals after treatment in 21 cats. Serum T4 concentrations also were measured one month after 131 I therapy in 29 cats. Activity of 131I administered was 1.5 to 6.13 mCi, resulting in a dose of 20,000 rads to the thyroid. Serum T4 concentrations before 131 I administration were 5.3 to 51.0 micrograms/dl, with a median T4 concentration of 11.0 micrograms/dl. Serum T4 decreased most rapidly during the first 3 to 6 days after treatment. Sixteen cats (55%) had normal serum thyroxine concentrations by day 4 after 131I administration, and 23 cats (74%) were euthyroxinemic by day 8 after treatment. One month after administration of 131I, the 29 cats evaluated were clinically improved, and 24 (83%) of the 29 cats evaluated had normal serum T4 concentrations, 3 cats (10%) remained hyperthyroxinemic, and 2 cats (7%) were hypothyroxinemic. Therefore, administration of 131I was a safe and effective method to quickly decrease serum T4 concentrations in hyperthyroid cats

Prediction of response to continuous irradiation at low dose rate for repeated administrations in radiotherapy with beta emitters

International Nuclear Information System (INIS)

Calderon, Carlos; Gonzalez, Joaquin; Quesada, Waldo

2009-01-01

The absorbed dose to tumors after systemic administration of radiopharmaceuticals is not sufficient to achieve acceptable levels of probability of tumor control without compromising on critical tissue toxicity (kidney and / or bone marrow (BM)). There are reports of trials with multiple administrations, about tolerance level inter-administration intervals to allow recovery of the BM, with good results. The biokinetic behavior of some radiopharmaceuticals known makes possible the application of several administrations with short intervals of time.It is the present work combines two kinetic models of tumor growth and cell kinetics in the BM for predicting the response to continuous irradiation at low dose rate. The estimation of the effects of irradiation on tumor and kidneys was done using a formulation of the linear-quadratic model functions suitable for dose rate and multi-exponential repair. The estimation of the response in WB performed using a compartmental model previously reported. The absorbed dose to organs were calculated using the MIRD formulation taking into account the effect of irradiation cross. Biokinetic data were used for therapeutic radiopharmaceuticals 90Y, 131I and 177Lu, as well as radiobiological parameters reported for experimental animals. The effect on the response by the variation of inter-administration interval in slow-growing tumors and fast, so as the radiosensitive and radioresistant tumors. You can set conditions irradiation to an acceptable level of thrombocytopenia (onset and duration of the minimum in the curve) and renal irradiation below the limit of tolerance. It is possible to design experiments evaluation of therapeutic radiopharmaceuticals with a greater degree of refinement. (author)

Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration

OpenAIRE

McFadden, Lisa M; Hoonakker, Amanda J; Vieira-Brock, Paula L; Stout, Kristen A; Sawada, Nicole M; Ellis, Jonathan D; Allen, Scott C; Walters, Elliot T; Nielsen, Shannon M; Gibb, James W; Alburges, Mario E; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

2011-01-01

Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent (i.e., postnatal day (PND) 40) rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a “challenge” high-dose METH regimen when administered ...

Plasma concentrations of misonidazole

Energy Technology Data Exchange (ETDEWEB)

Notter, G; Rylander, U; Turesson, I

1980-10-01

The plasma concentrations of misonidazole doses between 0.6 and 2.0 g/m/sup 2/ were analyzed in respect to the variation within the same patient and between different patients. Peak plasma levels were observed after 2 hours. The mean plasma levels of misonidazole only at 3 hours were 23.8, 47.0 and 76.5 ..mu..g/ml after misonidazole doses of 0.6, 1.2 g/m/sup 2/, respectively. The half-life of misonidazole only was found to be 8.2 hours for women and 10.5 for men. Good linearity between plasma levels and drug doses was observed after administration of different single doses to the same patient within the dose range 0.6 to 2.0 g/m/sup 2/.

Variability of linezolid concentrations after standard dosing in critically ill patients: a prospective observational study

Science.gov (United States)

2014-01-01

Introduction Severe infections in intensive care patients show high morbidity and mortality rates. Linezolid is an antimicrobial drug frequently used in critically ill patients. Recent data indicates that there might be high variability of linezolid serum concentrations in intensive care patients receiving standard doses. This study was aimed to evaluate whether standard dosing of linezolid leads to therapeutic serum concentrations in critically ill patients. Methods In this prospective observational study, 30 critically ill adult patients with suspected infections received standard dosing of 600 mg linezolid intravenously twice a day. Over 4 days, multiple serum samples were obtained from each patient, in order to determine the linezolid concentrations by liquid chromatography tandem mass spectrometry. Results A high variability of serum linezolid concentrations was observed (range of area under the linezolid concentration time curve over 24 hours (AUC24) 50.1 to 453.9 mg/L, median 143.3 mg*h/L; range of trough concentrations (Cmin) linezolid concentrations over 24 hours and at single time points (defined according to the literature as AUC24  400 mg*h/L and Cmin > 10 mg/L) were observed for 7 of the patients. Conclusions A high variability of linezolid serum concentrations with a substantial percentage of potentially subtherapeutic levels was observed in intensive care patients. The findings suggest that therapeutic drug monitoring of linezolid might be helpful for adequate dosing of linezolid in critically ill patients. Trial registration Clinicaltrials.gov NCT01793012. Registered 24 January 2013. PMID:25011656

Blood volume measurement with indocyanine green pulse spectrophotometry: dose and site of dye administration

NARCIS (Netherlands)

Germans, Menno R.; de Witt Hamer, Philip C.; van Boven, Leonard J.; Zwinderman, Koos A. H.; Bouma, Gerrit J.

2010-01-01

(1) To determine the optimal administration site and dose of indocyanine green (ICG) for blood volume measurement using pulse spectrophotometry, (2) to assess the variation in repeated blood volume measurements for patients after subarachnoid hemorrhage and (3) to evaluate the safety and efficacy of

Neuroprotection and mechanisms of atractylenolide III in preventing learning and memory impairment induced by chronic high-dose homocysteine administration in rats.

Science.gov (United States)

Zhao, H; Ji, Z-H; Liu, C; Yu, X-Y

2015-04-02

Studies demonstrated that chronic high-dose homocysteine administration induced learning and memory impairment in animals. Atractylenolide III (Aen-III), a neuroprotective constituent of Atractylodis macrocephalae Koidz, was isolated in our previous study. In this study, we investigated potential benefits of Aen-III in preventing learning and memory impairment following chronic high-dose homocysteine administration in rats. Results showed that administration of Aen-III significantly ameliorated learning and memory impairment induced by chronic high-dose homocysteine administration in rats, decreased homocysteine-induced reactive oxygen species (ROS) formation and restored homocysteine-induced decrease of phosphorylated protein kinase C expression level. Moreover, Aen-III protected primary cultured neurons from apoptotic death induced by homocysteine treatment. This study provides the first evidence for the neuroprotective effect of Aen-III in preventing learning and impairment induced by chronic administration of homocysteine. Aen-III may have therapeutic potential in treating homocysteine-mediated cognitive impairment and neuronal injury. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Variability in dose-equivalent assessments for inhaled U3O8 concentrations

International Nuclear Information System (INIS)

Hewson, G.; Blyth, D.I.

1985-01-01

A potentially significant radiological hazard exists in the packaging area of uranium mills through the inhalation of airborne uranium octoxide (U 3 O 8 ). The Radiation Protection (Mining and Milling Code (1980) requires the measurement and assessment of quarterly, annual and cumulative dose equivalents for employees working in these areas. Arising through differences which exist between the abovementioned Code and ICRP 30, and assumptions of particle size and dust concentration distributions, confusion exists within Australia regarding the methods which can be used to make the required assessments. Exposure data were collected during routine monitoring at an operating mill facility and were interpreted using different methods and a range of assumptions. Results indicated the dust at this facility is characterised by an AMAD greater than 10 μ, and dust concentrations were distributed lognormally. Assumptions of a normal distribution may result in an overestimate of the dose equivalent. The importance of particle size in dose assessments using ICRP 30 techniques was highlighted. Information was masked when employee data was grouped to provide work category dose assessments. The use of ICRP 30 methods were recommended to provide uniformity throughout Australia

Pb-210 concentrations in cigarettes tobaccos and radiation doses to the smokers

International Nuclear Information System (INIS)

Tahir, S.N.A.; Alaamer, A.S.

2008-01-01

Cigarette smoking is a source of radiation exposure due to the concentrations of natural radionuclides in the tobacco leaves. From the health point of view, measurement of 210 Pb and 210 Po contents in cigarette tobacco is important to assess the radiological effects associated with the tobacco smoking for the smokers. In the present study, activity concentrations of 210 Pb, which is a 210 Po precursor in the 238 U-decay series, were measured in cigarette tobaccos. Samples of nine different commonly sold brands of cigarette tobaccos were analysed by employing a planar high purity germanium (HPGe) low background detector. Activity concentrations of 210 Pb were measured from its gamma peak at 47 keV. Mean activity concentration of 210 Pb was measured to be 13 ± 4 Bq kg -1 from all samples analysed. The annual committed effective dose for a smoker and the collective committed effective dose corresponding to annual cigarettes production were estimated to be 64 ± 20 μSv and 0.6 x 10 2 man-Sv, respectively. (authors)

Disposition kinetics of long acting moxifloxacin following intravenous administration in Sheep

Directory of Open Access Journals (Sweden)

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

Internal dose assessment in nuclear medicine: fetal doses due to radiopharmaceutical administration to the mother

International Nuclear Information System (INIS)

Rojo, Ana M.; Michelin, Severino C.

2004-01-01

The objective of this publication is to present a guideline for the dose assessment through a comprehensive introduction of knowledge on ionizing radiation, radiation protection during pregnancy and fetal dosimetry for physician and other professionals involved in nuclear medicine practices. It contains tables with recommended dose estimates at all stages of pregnancy for many radiopharmaceuticals. Compounds for which some information was available regarding placental crossover are shown in shaded rows. It includes the most common diagnostic and therapy practices in nuclear medicine considering the four radioactive isotopes selected: 99m Tc, 131 I, 201 Tl and 67 Ga. There is a special case included, it is when conception occurs after the iodine has been administered. In almost every case, the diagnostic benefit to the mother outweighs the risk of any irradiation of the fetus. However, there is one situation in which severe fetal injury can be incurred from administering a radiopharmaceutical to the mother, and that is use of iodine-131 therapy for ablation of the thyroid in cases of hyperthyroidism or carcinoma. Radioactive iodine readily crosses the placenta and concentrates in the fetal thyroid, where, because of its small organ mass, high radiation doses are received. (author)

Retrospective evaluation of the effects of administration of tetrastarch (hydroxyethyl starch 130/0.4) on plasma creatinine concentration in dogs (2010-2013): 201 dogs.

Science.gov (United States)

Yozova, Ivayla D; Howard, Judith; Adamik, Katja-Nicole

2016-07-01

To determine changes in creatinine concentrations following the administration of 6% tetrastarch (hydroxyethyl starch [HES] 130/0.4) compared to crystalloids (CRYSs) in critically ill dogs. Retrospective case series (2010-2013). University teaching hospital. Two hundred and one dogs admitted to the intensive care unit with initial plasma creatinine concentrations not exceeding laboratory reference intervals (52-117 μmol/L [0.6-1.3 mg/dL]) and receiving either CRYSs alone (CRYS group, n = 115) or HES with or without CRYSs (HES group, n = 86) for at least 24 hours. None. Creatinine concentrations at admission to the intensive care unit (T0), and 2-13 days (T1) and 2-12 weeks (T2) after initiation of fluid therapy were analyzed. Creatinine concentrations were analyzed as absolute values and as the maximum percentage change from T0 to T1 (T1max%) and from T0 to T2 (T2max%), respectively. Creatinine concentrations were available for 192 dogs during T1 and 37 dogs during T2. The median cumulative dose of HES was 86 mL/kg (range, 12-336 mL/kg). No difference was detected between the groups for age, gender, body weight, and length of hospitalization. Outcome was significantly different between the HES (66% survived) and the CRYS (87% survived) groups (P = 0.014). No significant difference was detected between groups for creatinine concentrations at T0, T1, T2, T1max%, or T2max%. No significant difference was detected between the groups for T1max% creatinine in dogs subclassified as having systemic inflammatory response syndrome or sepsis. HES administration in this canine population did not result in increased creatinine concentrations compared to administration of CRYSs. Further studies are needed to establish the safety of HES in critically ill dogs. © Veterinary Emergency and Critical Care Society 2016.

A method for calculation of dose per unit concentration values for aquatic biota

International Nuclear Information System (INIS)

Batlle, J Vives i; Jones, S R; Gomez-Ros, J M

2004-01-01

A dose per unit concentration database has been generated for application to ecosystem assessments within the FASSET framework. Organisms are represented by ellipsoids of appropriate dimensions, and the proportion of radiation absorbed within the organisms is calculated using a numerical method implemented in a series of spreadsheet-based programs. Energy-dependent absorbed fraction functions have been derived for calculating the total dose per unit concentration of radionuclides present in biota or in the media they inhabit. All radionuclides and reference organism dimensions defined within FASSET for marine and freshwater ecosystems are included. The methodology has been validated against more complex dosimetric models and compared with human dosimetry based on ICRP 72. Ecosystem assessments for aquatic biota within the FASSET framework can now be performed simply, once radionuclide concentrations in target organisms are known, either directly or indirectly by deduction from radionuclide concentrations in the surrounding medium

Increased Serum and Urinary Oxytocin Concentrations after Nasal Administration in Beagle Dogs

Directory of Open Access Journals (Sweden)

Andrea Temesi

2017-09-01

Full Text Available In recent years more and more studies have revealed the effect of extraneous oxytocin on the social behavior of dogs. The distribution of administered oxytocin in different physiologically relevant compartments is important because this knowledge forms the basis for the timing of behavior tests after the administration. Most behavioral studies rely on the non-invasive intranasal application of oxytocin. The aim of this study was to determine the time course of intranasal administered oxytocin secretion into blood and urine and also establish a connection between intranasal received oxytocin and urinary cortisol in dogs. In our experiment, four dogs received three puffs, 12 IU intranasal oxytocin treatment, two dogs received three puffs intranasal placebo treatment. Blood and urine samples were collected immediately prior to the administration then regularly during 4 h. After nasal oxytocin application, the serum oxytocin concentration increased, reached a maximum 15 min after the treatment and then rapidly returned to baseline levels 45 min later. The peak urinary oxytocin concentration occurred between 45 and 60 min after administration and returned to baseline levels slowly. We found considerable differences among individuals in the secretion of oxytocin in both the serum and the urinary oxytocin concentration measurements. Our results confirm that intranasally administered oxytocin passes into the blood stream. The time course of intranasally administered oxytocin secretion is similar to the time course of intravenously administered oxytocin secretion, and the peak values are also similar in both the serum and the urinary oxytocin concentration measurements, although there are large individual differences.

Comparative pharmacokinetics of a fixed-dose combination vs concomitant administration of telmisartan and S-amlodipine in healthy adult volunteers

Directory of Open Access Journals (Sweden)

Oh M

2017-12-01

Full Text Available Minkyung Oh,1,2,* Sung-Eun Park,3,* Jong-Lyul Ghim,1–3 Young-Kyung Choi,1 Eon-Jeong Shim,1–3 Jae-Gook Shin,1–3 Eun-Young Kim1–3 1Department of Pharmacology, 2PharmacoGenomics Research Center, Inje University College of Medicine, Busan, 3Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea *These authors contributed equally to this work Objective: This study compared the pharmacokinetic (PK and safety profiles of a fixed-dose combination (FDC formulation of telmisartan and S-amlodipine with those of concomitant administration of the two drugs.Materials and methods: This was an open-label, randomized, crossover study in healthy male Koreans. All subjects were administered an FDC tablet containing 40 mg telmisartan and 5 mg S-amlodipine and were also coadministered the same dose of both drugs given separately. The crossover study design included a 14-day washout period between the two treatments. Blood samples were collected up to 168 h following drug administration. The plasma concentrations of telmisartan and S-amlodipine were determined by liquid chromatography tandem mass spectrometry. PK parameters and plasma concentration–time curves were compared. Safety was assessed by measuring vital signs, clinical laboratory tests, physical examinations, and patient interviews.Results: The geometric mean ratios and 90% CIs for the maximum plasma concentration (Cmax and area under the curve from time zero to the last sampling time (AUCt were 0.8782 (0.8167–0.9444 and 0.9662 (0.9210–1.0136 for telmisartan and 1.0069 (0.9723–1.0427 and 1.0324 (0.9969–1.0690 for S-amlodipine, respectively. A total of 36 adverse events (AEs were reported by 23 subjects, but no statistical differences were observed between the two treatments. The most frequently reported AE was a mild-to-moderate headache that was generally self-limiting.Conclusion: For both telmisartan and S-amlodipine, the Cmax and AUCt 90% CIs

Pharmacokinetics of [14C]teicoplanin in male rats after single intravenous dose

International Nuclear Information System (INIS)

Bernareggi, A.; Cavenaghi, L.; Assandri, A.

1986-01-01

The pharmacokinetic profile of [ 14 C]teicoplanin was studied in male Sprague-Dawley rats given a single 10,000-U/kg intravenous dose. The disposition of the antimicrobial activity in the body was estimated by a three-compartment open model. Plasma concentration data were fitted to a three-exponent equation. The profile of total 14 C in plasma was similar to that of the microbiological activity. The cumulative recovery of total 14 C 5 days after drug administration averaged 76.3% of the administered dose in the urine and 8.7% in the feces. The residual dose remaining in the animal carcasses was 11.1%. Teicoplanin was widely distributed in the body. In almost all organs, the maximum concentration of [ 14 C]teicoplanin was already reached at the first time of killing, which was 0.25 h after the administration of drug. The liver, kidneys, skin, and fat contained most of the residual dose found in the animal carcasses 120 h after administration and behaved as a deep compartment with the adrenal glands and spleen

The route of administration (oral vs intravenous) does not influence dose or outcome in Graves' disease and unifocal autonomy

International Nuclear Information System (INIS)

Schneider, Peter; Biko, Johannes; Haenscheid, Heribert; Hilliger, Stephan; Koutsampelas, Christos; Kranzfelder, Michael; Ladner, Stephan; Reiners, Christoph

2005-01-01

In a prospective randomised study, we investigated the influence of the route of administration of radioiodide on dosimetry and therapy outcome. Fifty-four patients suffering from Graves' disease (GD) and 60 patients with unifocal autonomy (UA) participated in the study and were randomly treated with either orally or intravenously administered radioiodide. Pretherapeutic dosimetry was based on single uptake measurements with a calibrated uptake probe system. The radioiodine kinetics during hospitalisation was assessed by daily bedside uptake measurements. Therapeutic dose was determined by half-life and thyroid uptake at the time of discharge using the same uptake probe as for the radioiodine test. No improvement in accuracy of dosimetry was achieved when radioiodide was administered intravenously. Mean therapeutic doses were identical following intravenous or oral administration. Variation in the achieved dose was slightly higher in the patients receiving oral administration, this being attributable to larger deviations in discrete activities of the capsules administered as compared with the values determined by dosimetry. No differences according to treatment modality were found with regard to therapeutic outcome. Eighty-seven patients attended 6-month follow-up after therapy. In the UA group, successful treatment, defined as a normal or elevated TSH level, was observed in 94% of patients after oral administration and in 80% after intravenous administration; corresponding figures in the GD group were 68% and 65%. The causes of individual differences between targeted and therapeutically achieved doses remain undetermined. Variations in the bioavailability of radioiodide or other parameters affecting thyroid status may be involved, and further investigations are needed to clarify this. (orig.)

Radon Concentration in Caves of Croatia - Assesing Effective Radon Doses for Occupational Workers and Visitors

International Nuclear Information System (INIS)

Radolic, V.; Miklavcic, I.; Poje, M.; Stanic, D.; Vukovic, B.; Paar, D.

2011-01-01

Radon monitoring at potentially highly radioactive location such as caves is important to assess the radiological hazards to occupational workers and occasional visitors. In its Publication 65 the ICRP has produced recommendations dealing with exposure to elevated background radiation, in particular, the risk associated with the inhalation of radon and radon progeny. Recommended annual effective dose from radon 222Rn and its short-lived progeny for workers should not exceed 20 mSv and for occasional users (visitors) the same recommendation is 1 mSv. Measurements were performed with series of track etched detectors (LR115 - type II) in several caves in Croatia. The obtained values for the radon concentration ranged from ambient values up to several thousand Bq m -3 . Radon concentration was measured in about 20 caves of Velebit and Zumberak mountains and the highest radon concentration was in Lubuska jama (3.8 kBq m -3 ) and cave Dolaca (21.8 kBq m -3 ), respectively. Djurovica cave is especially interesting because of its huge tourist potential due to its location bellow Dubrovnik airport. Its mean annual radon concentration of 17.6 kBq m -3 classifies Djurovica cave among caves with high radon concentration. A visitor during half an hour visit at summer time would receive an effective dose of 30.6 μSv. Calculated mean dose rate of 44 μSv/h means that workers (mainly tourist guides) should limit their time inside cave to 454 hours per year. Manita pec is the only cave open for tourists on the territory of Paklenica National Park. The preliminary radon measurements performed during summer 2010, gave an average radon concentration of 1.1 kBq m -3 . An exposure to average dose rate of 3.7 μSv/h means that the tourist guides would receive an effective dose of 0.42 mSv during summer period according to their working schedule. A visitor during half an hour visits would receive an effective dose of 1.86 μSv. (author)

Plasma concentrations of midazolam during continuous subcutaneous administration in palliative care.

Science.gov (United States)

Bleasel, M D; Peterson, G M; Dunne, P F

1994-01-01

We have investigated the steady-state plasma concentrations of midazolam during continuous subcutaneous administration in palliative care. Using a sensitive gas chromatography with electron capture detector assay, plasma concentrations of midazolam were measured in 11 patients (median age 68 years; range 47-82 years; six females) receiving the drug by continuous subcutaneous infusion (median rate 20 mg/day; range 10-60 mg/day). While not significant, the infusion rate tended to decrease with increasing age of the patient (Spearman's p = -0.51; p = 0.11). The steady-state plasma concentration range was 10-147 ng/ml, with a median of 30 ng/ml. Infusion rates and plasma concentrations of midazolam were correlated (Spearman's p = 0.71; p < 0.05). No other significant relationships were found between plasma concentrations and the variables of age, sex and liver function.

Variation of indoor radon concentration and ambient dose equivalent rate in different outdoor and indoor environments

Energy Technology Data Exchange (ETDEWEB)

Stojanovska, Zdenka; Janevik, Emilija; Taleski, Vaso [Goce Delcev University, Faculty of Medical Sciences, Stip (Macedonia, The Former Yugoslav Republic of); Boev, Blazo [Goce Delcev University, Faculty of Natural and Technical Sciences, Stip (Macedonia, The Former Yugoslav Republic of); Zunic, Zora S. [University of Belgrade, Institute of Nuclear Sciences ' ' Vinca' ' , Belgrade (Serbia); Ivanova, Kremena; Tsenova, Martina [National Center of Radiobiology and Radiation Protection, Sofia (Bulgaria); Ristova, Mimoza [University in Ss. Cyril and Methodius, Faculty of Natural Sciences and Mathematic, Institute of Physics, Skopje (Macedonia, The Former Yugoslav Republic of); Ajka, Sorsa [Croatian Geological Survey, Zagreb (Croatia); Bossew, Peter [German Federal Office for Radiation Protection, Berlin (Germany)

2016-05-15

Subject of this study is an investigation of the variations of indoor radon concentration and ambient dose equivalent rate in outdoor and indoor environments of 40 dwellings, 31 elementary schools and five kindergartens. The buildings are located in three municipalities of two, geologically different, areas of the Republic of Macedonia. Indoor radon concentrations were measured by nuclear track detectors, deployed in the most occupied room of the building, between June 2013 and May 2014. During the deploying campaign, indoor and outdoor ambient dose equivalent rates were measured simultaneously at the same location. It appeared that the measured values varied from 22 to 990 Bq/m{sup 3} for indoor radon concentrations, from 50 to 195 nSv/h for outdoor ambient dose equivalent rates, and from 38 to 184 nSv/h for indoor ambient dose equivalent rates. The geometric mean value of indoor to outdoor ambient dose equivalent rates was found to be 0.88, i.e. the outdoor ambient dose equivalent rates were on average higher than the indoor ambient dose equivalent rates. All measured can reasonably well be described by log-normal distributions. A detailed statistical analysis of factors which influence the measured quantities is reported. (orig.)

Topical administration of regorafenib eye drops: phase I dose-escalation study in healthy volunteers.

Science.gov (United States)

Zimmermann, Torsten; Höchel, Joachim; Becka, Michael; Boettger, Michael K; Rohde, Beate; Schug, Barbara; Kunert, Kathleen S; Donath, Frank

2018-05-01

Regorafenib is a multikinase inhibitor under investigation for use in neovascular age-related macular degeneration. In this phase I study, regorafenib eye drops were administered to healthy volunteers to provide information on safety, tolerability and systemic exposure. This was a single-centre, randomized, double-masked, parallel-group, dose-escalation, placebo-controlled study. Subjects received regorafenib eye drops (30 mg ml -1 , 25 μl) as a 0.75 mg single dose (Cohort 1), 0.75 mg twice daily (bid) or thrice daily (tid) over 14 days (Cohorts 2 and 3, respectively), 1.5 mg tid unilaterally for 3 days, then bilaterally for up to 14 days (Cohort 4), or placebo. Plasma samples were taken to estimate systemic exposure. Safety and functional assessments were performed throughout the study. Thirty-six subjects received regorafenib and 12 received placebo. Regorafenib was safe and well tolerated over the dose range. No pathological changes occurred in the anterior, vitreous or posterior eye compartments. Mild eyelid redness, oedema and conjunctival hyperaemia were observed across all regorafenib cohorts; these were comparable with the effects seen with placebo. Predominant symptoms were blurred vision in the active and placebo groups. Systemic safety evaluations showed no clinically relevant findings. Absolute systemic exposure after multiple administrations of regorafenib eye drops at a dose of 0.75 mg was 600-700-fold lower than after multiple oral administration of 160 mg day -1 , the dose approved in cancer indications. These results indicate a favourable safety and tolerability profile of regorafenib eye drops up to 30 mg ml -1 tid for use in clinical studies. © 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Histology and Gadolinium Distribution in the Rodent Brain After the Administration of Cumulative High Doses of Linear and Macrocyclic Gadolinium-Based Contrast Agents

Science.gov (United States)

Lohrke, Jessica; Frisk, Anna-Lena; Frenzel, Thomas; Schöckel, Laura; Rosenbruch, Martin; Jost, Gregor; Lenhard, Diana Constanze; Sieber, Martin A.; Nischwitz, Volker; Küppers, Astrid; Pietsch, Hubertus

2017-01-01

Objectives Retrospective studies in patients with primary brain tumors or other central nervous system pathologies as well as postmortem studies have suggested that gadolinium (Gd) deposition occurs in the dentate nucleus (DN) and globus pallidus (GP) after multiple administrations of primarily linear Gd-based contrast agents (GBCAs). However, this deposition has not been associated with any adverse effects or histopathological alterations. The aim of this preclinical study was to systematically examine differences between linear and macrocyclic GBCAs in their potential to induce changes in brain and skin histology including Gd distribution in high spatial resolution. Materials and Methods Fifty male Wistar-Han rats were randomly allocated into control (saline, n = 10 rats) and 4 GBCA groups (linear GBCAs: gadodiamide and gadopentetate dimeglumine, macrocyclic GBCAs: gadobutrol and gadoteridol; n = 10 rats per group). The animals received 20 daily intravenous injections at a dose of 2.5 mmol Gd/kg body weight. Eight weeks after the last GBCA administration, the animals were killed, and the brain and skin samples were histopathologically assessed (hematoxylin and eosin; cresyl violet [Nissl]) and by immunohistochemistry. The Gd concentration in the skin, bone, brain, and skeletal muscle samples were analyzed using inductively coupled plasma mass spectroscopy (ICP-MS, n = 4). The spatial Gd distribution in the brain and skin samples was analyzed in cryosections using laser ablation coupled with ICP-MS (LA-ICP-MS, n = 3). For the ultra-high resolution of Gd distribution, brain sections of rats injected with gadodiamide or saline (n = 1) were assessed by scanning electron microscopy coupled to energy dispersive x-ray spectroscopy and transmission electron microscopy, respectively. Results No histological changes were observed in the brain. In contrast, 4 of 10 animals in the gadodiamide group but none of the animals in other groups showed macroscopic and histological

Northern Marshall Islands radiological survey: radionuclide concentrations in fish and clams and estimated doses via the marine pathway

International Nuclear Information System (INIS)

Robison, W.L.; Noshkin, V.E.; Phillips, W.A.; Eagle, R.J.

1981-01-01

The survey consisted, in part, of an aerial radiological reconnaissance to map the external gamma-ray exposure rates. As a secondary phase, terrestrial and marine samples were collected to assess the radiological dose from pertinent food chains to atoll inhabitants. The marine sample collection, processing, and dose assessment methodology are presented as well as the concentration data for 90 Sr, 137 Cs, 238 Pu, 239+240 Pu, 241 Am, and any of the other gamma emitters in fish and clam muscle tissue from the different species collected. Doses are calculated from the average radionuclide concentrations in fish and clam muscle tissue assuming an average daily intake of 200 and 10 g, respectivelty. The 90 Sr concentration in muscle tissue is very low and there is little difference in the average concentrations from the different fish from different atolls or islands. The 239+240 Pu concentration in the muscle tissue of all reef species, however, is higher than that in pelagic lagoon fish. In contrast, 137 Cs concentrations are lowest in the muscle tissue of the bottom-feeding reef species and highest in pelagic logoon fish. Recent measurements of radionuclide concentrations in fish muscle tissue and other marine dietary items from international sources show that the average concentrations in species from the Marshall Islands are comparable to those in fish typically consumed as food in the United States and are generally lower than those in most international marine dietary items. The whole-body dose rates based on continuous consumption of 200 g/d of fish range from 0.028 to 0.1 mrem/y; the bone-marrow dose rates range from 0.029 to 0.12 mrem/y. The dose commitment, or 30-y integral doses, range from 0.00063 to 0.0022 rem for the whole body and from 0.00065 to 0.0032 rem for the bone marrow

Micro-dose hCG as luteal phase support without exogenous progesterone administration

DEFF Research Database (Denmark)

Andersen, C Yding; Fischer, R; Giorgione, V

2016-01-01

RHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple......For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the Gn...... corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential...

Individual doses control in the units of ministry of defence and ministry of interior and administration in the years 1986 - 2000

International Nuclear Information System (INIS)

Jazwinski, J.; Nowosielska, E.M.; Janiak, M.K.

2003-01-01

The aim of presented work was the assessment of occupational radiation exposure and its distribution among the workers of Ministry of Defence and Ministry of Interior and Administration in the years 1986 - 2000. the research was conducted on the basis of data collected by Laboratory of Radiological Inspection and Individual Doses Control, Department of Radiation Protection and Radiobiology Military Institute of Hygiene and Epidemiology, Warsaw, Poland. The workers occupationally exposed to radiation were divided into following groups: government department (Ministry of Defence or Ministry of Interior and Administration), according to the age (below 25, 26-35, 36-45, 46-55 and above 56 years old), sex, education, (elementary, secondary, university) or job (doctors, nurses, rtg technicians, etc.). The number of workers covered with individual doses control changed in Ministry of Defence from 689 (in 1986) to 1030 (in 2000), and in Ministry of Interior and Administration from 261 to 924 in the same period. The percent of workers, who received doses below 2 mSv per year varied in Ministry of Defence from 91,6% (in 1997) to 99,4% (in 1990), and in Ministry of Interior and Administration from 96,8% (in 1993) to 99,4 (in 2000). Almost 99% of workers occupationally exposed to radiation and covered with individual doses control received doses below 15 mSv, irrespective of year or department. The analysis of collected data revealed, that for a large majority of occupationally exposed workers the risk arising from contact with ionizing radiation is minimal (over 99% of workers covered with individual doses control received doses below 2 mSv per year), however there are critical groups of workers, for which the received equivalent doses were about 30 - 50 mSv. Increased doses of radiation, however not exceeding obligatory limits, are noticed for workers taking part in surgical operations in X radiation field, urologic operations and diagnostic and or working on several

Impact of benzodiazepines on brain FDG-PET quantification after single-dose and chronic administration in rats

International Nuclear Information System (INIS)

Silva-Rodríguez, Jesús; García-Varela, Lara; López-Arias, Esteban; Domínguez-Prado, Inés; Cortés, Julia; Pardo-Montero, Juan; Fernández-Ferreiro, Anxo

2016-01-01

Introduction: Current guidelines for brain PET imaging advice against the injection of diazepam prior to brain FDG-PET examination in order to avoid possible interactions of benzodiazepines with the radiotracer uptake. Nevertheless, many patients undergoing PET studies are likely to be under chronic treatment with benzodiazepines, for example due to the use of different medications such as sleeping pills. Animal studies may provide an extensive and accurate estimation of the effect of benzodiazepines on brain metabolism in a well-defined and controlled framework. Aim: This study aims at evaluating the impact of benzodiazepines on brain FDG uptake after single-dose administration and chronic treatment in rats. Methods: Twelve Sprague–Dawley healthy rats were randomly divided into two groups, one treated with diazepam and the other used as control group. Both groups underwent PET/CT examinations after single-dose and chronic administration of diazepam (treated) or saline (controls) during twenty-eight days. Different atlas-based quantification methods were used to explore differences on the total uptake and uptake patterns of FDG between both groups. Results: Our analysis revealed a significant reduction of global FDG uptake after acute (−16.2%) and chronic (−23.2%) administration of diazepam. Moreover, a strong trend pointing to differences between acute and chronic administrations (p < 0.08) was also observed. Uptake levels returned to normal after interrupting the administration of diazepam. On the other hand, patterns of FDG uptake were not affected by the administration of diazepam. Conclusions: The administration of diazepam causes a progressive decrease of the FDG global uptake in the rat brain, but it does not change local patterns within the brain. Under these conditions, visual assessment and quantification methods based on regional differences such as asymmetry indexes or SPM statistical analysis would still be valid when administrating this

Correlations of Maternal Buprenorphine Dose, Buprenorphine, and Metabolite Concentrations in Meconium with Neonatal Outcomes

Science.gov (United States)

Kacinko, SL; Jones, HE; Johnson, RE; Choo, RE; Huestis, MA

2009-01-01

For the first time, relationships among maternal buprenorphine dose, meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted meconium concentrations or neonatal outcomes. Total buprenorphine meconium concentrations and buprenorphine/norbuprenorphine ratios were significantly related to neonatal abstinence syndrome (NAS ) scores >4. As free buprenorphine concentration and percentage free buprenorphine increased, head circumference decreased. Thrice-weekly urine tests for opiates, cocaine, and benzodiazepines and self-reported smoking data from the mother were compared with data from analysis of the meconium to estimate in utero exposure. Time of last drug use and frequency of use during the third trimester were important factors associated with drug-positive meconium specimens. The results suggest that buprenorphine and metabolite concentrations in the meconium may predict the onset and frequency of NAS. PMID:18701886

Distribution of exposure concentrations and doses for constituents of environmental tobacco smoke

Energy Technology Data Exchange (ETDEWEB)

LaKind, J.S. [LaKind Associates (United States); Ginevan, M.E. [M.E. Ginevan and Associates (United States); Naiman, D.Q. [Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Mathematical Sciences; James, A.C. [A.C. James and Associates (United States); Jenkins, R.A. [Oak Ridge National Lab., TN (United States); Dourson, M.L.; Felter, S.P. [TERA (United States); Graves, C.G.; Tardiff, R.G. [Sapphire Group, Inc., Bethesda, MD (United States)

1999-06-01

The ultimate goal of the research reported in this series of three articles is to derive distributions of doses of selected environmental tobacco smoke (ETS)-related chemicals for nonsmoking workers. This analysis uses data from the 16-City Study collected with personal monitors over the course of one workday in workplaces where smoking occurred. In this article, the authors describe distributions of ETS chemical concentrations and the characteristics of those distributions for the workplace exposure. Next, they present population parameters relevant for estimating dose distributions and the methods used for estimating those dose distributions. Finally, they derive distributions of doses of selected ETS-related constituents obtained in the workplace for people in smoking work environments. Estimating dose distributions provided information beyond the usual point estimate of dose and showed that the preponderance of individuals exposed to ETS in the workplace were exposed at the low end of the dose distribution curve. The results of this analysis include estimations of hourly maxima and time-weighted average (TWA) doses of nicotine from workplace exposures to ETS and doses derived from modeled lung burdens of ultraviolet-absorbing particulate matter (UVPM) and solanesol resulting from workplace exposures to ETS (extrapolated from 1 day to 1 year).

Continuous infusion vs. bolus dosing: implications for beta-lactam antibiotics.

Science.gov (United States)

Mohd Hafiz, Abdul-Aziz; Staatz, C E; Kirkpatrick, C M J; Lipman, J; Roberts, J A

2012-01-01

Beta-lactam antibiotics display time-dependant pharmacodynamics whereby constant antibiotic concentrations rather than high peak concentrations are most likely to result in effective treatment of infections caused by susceptible bacteria. Continuous administration has been suggested as an alternative strategy, to conventional intermittent dosing, to optimise beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) properties. With the availability of emerging data, we elected to systematically investigate the published literature describing the comparative PK/PD and clinical outcomes of beta-lactam antibiotics administered by continuous or intermittent infusion. We found that the studies have been performed in various patient populations including critically ill, cancer and cystic fibrosis patients. Available in vitro PK/PD data conclusively support the administration of beta-lactams via continuous infusion for maximizing bacterial killing from consistent attainment of pharmacodynamic end-points. In addition, clinical outcome data supports equivalence, even with the use of a lower dose by continuous infusion. However, the present clinical data is limited with small sample sizes common with insufficient power to detect advantages in favour of either dosing strategy. With abundant positive pre-clinical data as well as document in vivo PK/PD advantages, large multi-centre trials are needed to describe whether continuous administration of beta-lactams is truly more effective than intermittent dosing.

Impact of Flow Rate, Collection Devices, and Extraction Methods on Tear Concentrations Following Oral Administration of Doxycycline in Dogs and Cats.

Science.gov (United States)

Sebbag, Lionel; Showman, Lucas; McDowell, Emily M; Perera, Ann; Mochel, Jonathan P

2018-04-30

Compare the precision of doxycycline quantification in tear fluid collected with either Schirmer strips or polyvinyl acetal (PVA) sponges following oral drug administration. Three dogs and 3 cats were administered doxycycline orally at a dose of 4.2-5 mg/kg every 12 h for 6 consecutive days. At day 5 and 6, blood and tear fluid were sampled to capture doxycycline trough and maximal concentrations. Tear fluid was collected 3 times (spaced 10 min apart) at each session with the absorbent material placed in the lower conjunctival fornix until the 20-mm mark was reached (Schirmer strip, one eye) or for 1 min (PVA sponge, other eye). Tear extraction was performed with either centrifugation or elution in methanol. Doxycycline concentrations were measured with liquid chromatography-mass spectrometry. Low (100 ng/mL) and high (1,000 ng/mL) tear concentrations measured in vivo were spiked into each absorbent material in vitro to evaluate percentage drug recovery. After oral administration of doxycycline, the drug reached the tear compartment at concentrations of 45.1-900.7 ng/mL in cats and 45.4-632.0 ng/mL in dogs, representing a tear-to-serum ratio of 12% and 16%, respectively. Doxycycline tear concentrations were significantly more precise when tear collection was performed with Schirmer strips rather than PVA sponges (P = 0.007), but were not correlated with tear flow rate. In vitro doxycycline recovery was poor to moderate (<75%). Schirmer strips represent a good option for lacrimal doxycycline quantification, although the collection and subsequent extraction have to be optimized to improve drug recovery.

Recommendations for the use of methotrexate in rheumatoid arthritis: up and down scaling of the dose and administration routes.

Science.gov (United States)

Tornero Molina, Jesús; Ballina García, Francisco Javier; Calvo Alén, Jaime; Caracuel Ruiz, Miguel Ángel; Carbonell Abelló, Jordi; López Meseguer, Antonio; Moreno Muelas, José Vicente; Pérez Sandoval, Trinidad; Quijada Carrera, Jesús; Trenor Larraz, Pilar; Zea Mendoza, Antonio

2015-01-01

To describe the optimal therapeutic strategy for use of methotrexate in RA patients over the initial dose, route of administration, dose increase and decrease, patient monitoring, and use of folic/folinic acid. Eleven clinical experts proposed some questions to be solved. A systematic literature search was conducted. The contents were selected in a work session and subsequently validated via email to establish the level of agreement. The initial dose of methotrexate should not be 20mg/week), patient preference, very active disease or to avoid administration errors. Changing to a parenteral administration is proposed when the oral route is not effective enough, gastrointestinal toxicity appears, there is non-compliance or due to cost-effectiveness reasons before using more expensive drugs. On the contrary, due to patient preferences, intolerance to injections, dose reduction <7.5mg/week, non effectiveness of the route, poor compliance or gastrointestinal side effects. There should be a rapid dose escalation if inadequate responses occurr up to 15-20 or even 25mg/week in about 8 weeks, with increments of 2.5-5mg. The reduction will be carried out according to the dose the patient had, with decreases of 2.5-5mg every 3-6 months. Patient monitoring should be performed every 1-1.5 months until stability and then every 1-3 months. This document pretends to solve some common clinical questions and facilitate decision-making in RA patients treated with methotrexate. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Impact of cytochrome p450 3A5 genetic polymorphism on tacrolimus doses and concentration-to-dose ratio in renal transplant recipients.

Science.gov (United States)

Thervet, Eric; Anglicheau, Dany; King, Barry; Schlageter, Marie-Hélène; Cassinat, Bruno; Beaune, Philippe; Legendre, Christophe; Daly, Ann K

2003-10-27

Tacrolimus pharmacokinetic characteristics vary greatly among individuals. Tacrolimus is a substrate of cytochrome p450 (CYP), of subfamily CYP3A. CYP3A activity is the sum of the activities of the family of CYP3A genes, including CYP3A5. Subjects with the CYP3A5*1/*1 genotype express large amounts of CYP3A5. Heterozygotes (genotype CYP3A5*1/*3) also express the enzyme. We postulated that CYP3A5 polymorphism is associated with tacrolimus pharmacokinetic variations. CYP3A5 genotype was evaluated in 80 renal transplant recipients and correlated with the daily tacrolimus dose and concentration-to-dose ratio. The frequency of the homozygous CYP3A5*1 genotype (CYP3A5*1/*1) was 5%, and 11% of subjects were heterozygous (CYP3A5*1/*3). The mean doses required to obtain the targeted concentration-to-dose ratio were significantly lower in patients with the CYP3A5*1/*1 genotype. Determination of CYP3A5 genotype is predictive of the dose of tacrolimus in renal transplant recipients and may help to determine the initial daily dose needed by individual patients for adequate immunosuppression without excess nephrotoxicity.

Dosing of Appropriate Antibiotics and Time to Administration of First Doses in the Pediatric Emergency Department.

Science.gov (United States)

Bailey, Abby M; Stephan, Maria; Weant, Kyle A; Justice, Stephanie Baker

2015-01-01

Emergency department (ED) providers are faced with the challenge of diagnosing and treating patients in a timely fashion given many obstacles including limited patient information, complex disease states, and high patient turnover. Time delays in administration or selection of appropriate drug therapies have been associated with negative outcomes in severe infections. This study was conducted to assess the impact of an emergency medicine pharmacist (EPh) on the selection of appropriate antibiotics and the timeliness of administration in pediatric patients in the ED. Patients younger than 18 years were evaluated who were admitted through the ED and received 1 dose of intravenous antibiotic for the following conditions: community-acquired pneumonia, complicated skin and soft tissue infection (SSTI), meningitis, and sepsis. To evaluate the impact of the presence of an EPh, patients with orders placed during the EPh's hours of 1 pm and 11 pm were compared to those with an order placed between 11 pm and 1 pm. A total of 142 patients were included in the study. Patients seen during EPh hours received an appropriate first antibiotic 93.4% of the time (p = 0.157) and second antibiotic 96.8% of the time (p = 0.023). Time from order to verification was significantly shorter for the first 2 antimicrobials in the EPh group (10.5 minutes [p = 0.003] and 11.4 minutes [p = 0.047], respectively). The days from discharge to return to readmission to the ED were also significantly different (17.5 days vs. 62.4 days, p = 0.008). The available data suggest that patients are more likely to receive appropriate doses of antimicrobials, and in a more timely fashion, whenever the EPh is present. Areas for future investigation include whether the presence of EPhs at the bedside has the potential to impact areas of patient care, including readmission rates, drug costs, and medication errors.

Effect of racemic ibuprofen dose on the magnitude and duration of platelet cyclo-oxygenase inhibition: relationship between inhibition of thromboxane production and the plasma unbound concentration of S(+)-ibuprofen.

Science.gov (United States)

Evans, A M; Nation, R L; Sansom, L N; Bochner, F; Somogyi, A A

1991-02-01

1. Four healthy male subjects received racemic ibuprofen (200, 400, 800 and 1200 mg), orally, on four occasions, 2 weeks apart, according to a four-way Latin-square design, in order to investigate the influence of increasing dose of ibuprofen on the magnitude and duration of its antiplatelet effect as well as on the relationship between such effect and drug concentration. 2. The antiplatelet effect of ibuprofen was assessed by measuring the inhibition of platelet thromboxane B2 (TXB2) generation during the controlled clotting of whole blood. The plasma unbound concentration of S(+)-ibuprofen, the enantiomer shown in an in vitro study to be responsible for the inhibitory effect of platelet TXB2 generation, was measured using an enantioselective method. 3. The maximum percentage inhibition of TXB2 generation increased significantly with dose from a mean +/- s.d. of 93.4 +/- 1.2% after the 200 mg dose to 98.8 +/- 0.3% after the 1200 mg dose, and there was an increase with dose in the duration of inhibition of TXB2 generation. The effect of ibuprofen on platelet TXB2 generation was transient and mirrored the time-course of unbound S(+)-ibuprofen in plasma; on all but one of the 16 occasions, serum TXB2 concentrations returned to at least within 10% of the pretreatment concentrations within 24 h of ibuprofen administration. 4. For each subject, the relationship between the percentage inhibition of TXB2 generation and the unbound concentration of S(+)-ibuprofen in plasma was modelled according to a sigmoidal Emax equation. The mean plasma unbound concentration of S(+)-ibuprofen required to inhibit platelet TXB2 generation by 50% (EC50) was 9.8 +/- 1.0 micrograms l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

The dose of nafamostat mesilate during plasma exchange with continuous hemodiafiltration in the series-parallel circuit.

Science.gov (United States)

Nakae, Hajime; Igarashi, Toshiko; Tajimi, Kimitaka

2006-06-01

We studied nafamostat mesilate (NM) and interleukin (IL)-18 levels to determine whether the dose of NM is reduced during plasma exchange (PE) with continuous hemodiafiltration (CHDF) when the series-parallel circuit is used. The subjects of the current study included four patients with acute hepatic failure who underwent PE with CHDF. The four patients underwent a total 15 PE + CHDF procedures, and for each procedure, they were randomized to receive either a half-dose of NM or no NM in the CHDF circuit. Eight procedures were carried out with NM administration, and seven were carried out without NM administration. The dose of NM in the NM group was significantly higher than that in the non-NM group (P = 0.040). No significant differences were observed between the two groups in the inlet NM concentration, the outlet NM concentration, or the rate of IL-18 removal. No statistical correlation was observed between the IL-18 level and the NM dose, the inlet NM concentration, or the outlet NM concentration. There was no blood access difficulty such as catheter failure or clotting of the filter. Thus, it might be possible to carry out PE and CHDF with the series-parallel method without administration of NM in the CHDF circuit.

Pill content, dose and resulting plasma concentrations of 3,4-methylendioxymethamphetamine (MDMA) in recreational 'ecstasy' users.

Science.gov (United States)

Morefield, Kate M; Keane, Michael; Felgate, Peter; White, Jason M; Irvine, Rodney J

2011-07-01

To improve our understanding of the pharmacology of 'ecstasy' in recreational environments; in particular, to describe the composition of ecstasy pills, patterns of ecstasy use and the relationship between dose of 3,4-methylendioxymethamphetamine (MDMA) and resulting plasma concentrations. A naturalistic observational study of 56 experienced 'ecstasy' users in recreational settings in Australia. Drug use patterns (number of pills consumed, other drugs consumed). drug content of pills and resultant plasma concentrations of MDMA and related drugs were assessed by gas chromatography/mass spectrometry (GC/MS). Ecstasy pills generally contained MDMA, but this was often combined with other drugs such as 3,4-ethylendioxyethylamphetamine (MDEA) and methamphetamine. The dose of MDMA per pill ranged from 0 to 245 mg and users consumed from one-half to five pills, with the total dose consumed ranging up to 280 mg. Plasma concentrations of MDMA increased with number of pills consumed and cumulative MDMA dose. Use of larger numbers of pills was associated with extended exposure to the drug. MDMA is the major active drug in ecstasy pills, but there is a high degree of variation in doses. Use of multiple pills over the course of one session is common and results in a sustained increase in MDMA plasma concentrations over a number of hours. This is likely to lead to a much greater exposure of the brain to MDMA than would be predicted from controlled single-dose pharmacokinetic studies. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Radon activity concentrations and effective doses in ancient Egyptian tombs of the Valley of the Kings

International Nuclear Information System (INIS)

Hafez, A.F.; Hussein, A.S.

2001-01-01

Radon concentrations and equilibrium factors were measured in three pharaonic tombs during the year 1998. The tombs, which are open to the public are located in a limestone wadi on the West Bank of the River Nile at Luxor, 650 km south of Cairo. The radon activity concentration and equilibrium factor were measured monthly by two-integral nuclear track detectors (bare and diffusion detectors). Seasonal variation of radon concentrations, with summer maximum and winter minimum were observed in all tombs investigated. The yearly mean radon activity concentrations inside the tombs ranged from 540 to 3115 Bq m -3 . The mean equilibrium factor over a year was found to be 0.25 and 0.32 inside and at the entrance, respectively. Estimated annual effective doses to tour guides ranged from 0.33 to 1.90 mSv, visitors receive doses from 0.65 to 3.80 μSv per visit. The effective dose to tomb workers did not exceed the 20 mSv yr -1 limit

Radon activity concentrations and effective doses in ancient Egyptian tombs of the Valley of the Kings.

Science.gov (United States)

Hafez, A F; Hussein, A S

2001-09-01

Radon concentrations and equilibrium factors were measured in three pharaonic tombs during the year 1998. The tombs, which are open to the public are located in a limestone wadi on the West Bank of the River Nile at Luxor, 650 km south of Cairo. The radon activity concentration and equilibrium factor were measured monthly by two-integral nuclear track detectors (bare and diffusion detectors). Seasonal variation of radon concentrations, with summer maximum and winter minimum were observed in all tombs investigated. The yearly mean radon activity concentrations insidc the tombs ranged from 540 to 3115 Bq m(-3). The mean equilibrium factor over a year was found to be 0.25 and 0.32 inside and at the entrance, respectively. Estimated annual effective doses to tour guides ranged from 0.33 to 1.90 mSv, visitors receive doses from 0.65 to 3.80 microSv per visit. The effective dose to tomb workers did not exceed the 20 mSv yr(-1) limit.

Radon activity concentrations and effective doses in ancient Egyptian tombs of the Valley of the Kings

Energy Technology Data Exchange (ETDEWEB)

Hafez, A F; Hussein, A S

2001-09-01

Radon concentrations and equilibrium factors were measured in three pharaonic tombs during the year 1998. The tombs, which are open to the public are located in a limestone wadi on the West Bank of the River Nile at Luxor, 650 km south of Cairo. The radon activity concentration and equilibrium factor were measured monthly by two-integral nuclear track detectors (bare and diffusion detectors). Seasonal variation of radon concentrations, with summer maximum and winter minimum were observed in all tombs investigated. The yearly mean radon activity concentrations inside the tombs ranged from 540 to 3115 Bq m{sup -3}. The mean equilibrium factor over a year was found to be 0.25 and 0.32 inside and at the entrance, respectively. Estimated annual effective doses to tour guides ranged from 0.33 to 1.90 mSv, visitors receive doses from 0.65 to 3.80 {mu}Sv per visit. The effective dose to tomb workers did not exceed the 20 mSv yr{sup -1} limit.

Bioavailability of oxycodone after administration of a new prolonged-release once-daily tablet formulation in healthy subjects, in comparison to an established twice-daily tablet
.

Science.gov (United States)

Scheidel, Bernhard; Maritz, Martina A; Gschwind, Yves J; Steigerwald, Kerstin; Guth, Volker; Kovacs, Peter; Rey, Helene

2017-11-01

To evaluate and to compare the bioavailability, the influence of food intake on the bioavailability, and the safety and tolerability of a newly-developed oxycodone once-daily (OOD) prolonged-release tablet with an established oxycodone twice-daily (OTD) prolonged-release tablet after single-dose administration under fasting or fed conditions as well as after multiple-dose administration. Three single-center, open-label, randomized, balanced, two-treatment, two-period, two-sequence crossover studies were conducted. In each study, 36 healthy volunteers were randomized to receive 10 mg oxycodone daily as OOD (oxycodone HCL 10-mg PR tablets XL (Develco Pharma Schweiz AG, Pratteln, Switzerland); administration of 1 tablet in the morning) or as OTD (reference formulation: oxygesic 5-mg tablets (Mundipharma GmbH, Limburg an der Lahn, Germany); administration of 1 tablet in the morning and 1 tablet in the evening). Tablets were administered once daily or twice daily under fasting conditions (study 1) or under fed conditions (study 2) as well as after multiple-dose administration (study 3). A sufficient number of blood samples were taken for describing plasma profiles and for calculation of pharmacokinetic parameters. Plasma concentrations of oxycodone were determined by LC-MS/MS. Safety and tolerability were monitored and assessed in all three studies. Plasma profiles of OOD reveal sustained concentrations of oxycodone over the complete dosing interval of 24 hours. In comparison to the OTD reference formulation, the OOD test formulation showed a slightly slower increase of concentrations within the absorption phase and similar plasma concentrations at the maximum and at the end of the dosing interval (24 hours). Extent of bioavailability (AUC), maximum plasma concentrations (Cmax), and plasma concentrations at the end of the dosing interval (Cτ,ss,24h) of OOD could be classified as comparable to OTD considering 90% confidence intervals (CIs) and acceptance limits of 80

Pharmacology of ayahuasca administered in two repeated doses.

Science.gov (United States)

Dos Santos, Rafael G; Grasa, Eva; Valle, Marta; Ballester, Maria Rosa; Bouso, José Carlos; Nomdedéu, Josep F; Homs, Rosa; Barbanoj, Manel J; Riba, Jordi

2012-02-01

Ayahuasca is an Amazonian tea containing the natural psychedelic 5-HT(2A/2C/1A) agonist N,N-dimethyltryptamine (DMT). It is used in ceremonial contexts for its visionary properties. The human pharmacology of ayahuasca has been well characterized following its administration in single doses. To evaluate the human pharmacology of ayahuasca in repeated doses and assess the potential occurrence of acute tolerance or sensitization. In a double-blind, crossover, placebo-controlled clinical trial, nine experienced psychedelic drug users received PO the two following treatment combinations at least 1 week apart: (a) a lactose placebo and then, 4 h later, an ayahuasca dose; and (b) two ayahuasca doses 4 h apart. All ayahuasca doses were freeze-dried Amazonian-sourced tea encapsulated to a standardized 0.75 mg DMT/kg bodyweight. Subjective, neurophysiological, cardiovascular, autonomic, neuroendocrine, and cell immunity measures were obtained before and at regular time intervals until 12 h after first dose administration. DMT plasma concentrations, scores in subjective and neurophysiological variables, and serum prolactin and cortisol were significantly higher after two consecutive doses. When effects were standardized by plasma DMT concentrations, no differences were observed for subjective, neurophysiological, autonomic, or immunological effects. However, we observed a trend to reduced systolic blood pressure and heart rate, and a significant decrease for growth hormone (GH) after the second ayahuasca dose. Whereas there was no clear-cut tolerance or sensitization in the psychological sphere or most physiological variables, a trend to lower cardiovascular activation was observed, together with significant tolerance to GH secretion.

222Radon concentration and irradiation dose inside the department of nuclear medicine in Wuhan

International Nuclear Information System (INIS)

Cheng Xiaoli; Wang Changyin; Gao Jianhua; Zou Xiaofeng

2002-01-01

Objective: Inspecting the high radioactivity area in department of nuclear medicine in Wuhan region and estimating the irradiation dose on relevant doctors. Methods: Select six 'three A' hospitals' high radioactivity area in department of nuclear medicine and common residential houses as examples. A half-year surveillance using 222 Rn detector (type LIH-2) was performed. Results: In high radioactivity rooms, imaging rooms residential houses, the average 222 Rn concentration are 27.8, 48.2, 27.1 (Bq·m -3 ) respectively. Effective dose equivalent absorbed by doctors in high radioactivity room and imaging room are 0.16 and 0.28 mSv. The authors estimated that the effective dose equivalent of doctors in these two room and common residents per year are 0.84, 0.70 and 0.64 mSv respectively. Conclusions: Doctors in imaging room and high radioactivity room are exposed to a relatively higher annual effective dose than common residents. But they are still within the normal range. Only two imaging rooms have high 222 Rn concentrations, which will cause potential harm

Biological fate of a single administration of 191Pt in rats following different routes of exposure

International Nuclear Information System (INIS)

Moore, W. Jr.; Hysell, D.; Crocker, W.; Stara, J.

1975-01-01

The retention, tissue distribution, and excretion of 191 Pt in adult rats was determined following oral, intravenous (IV), and intratracheal administration. The highest retention was obtained following IV dosing, and lowest retention (less than 0.5 percent) occurred after oral dosing. Tissues containing the highest concentrations of 191 Pt following IV administration were the kidney, adrenal, spleen, and liver. Following a single oral dose, almost all of the 191 Pt was excreted in the feces due to nonabsorption, whereas after IV dosing, similar quantities were excreted in both the urine and feces. Following IV dosing of pregnant rats, 191 Pt was found in all the fetuses; however, the amount was small

Determination of the total indicative dose in drinking and mineral waters

International Nuclear Information System (INIS)

Flesch, K.; Schulz, H.; Knappik, R.; Koehler, M.

2006-01-01

In Europe and Germany administrative regulations exist for the surveillance of the total indicative dose of water supplied for human consumption. This parameter, which cannot be analyzed directly, has to be calculated using nuclide specific activity concentration and age specific dose conversion factors and consumption rates. Available calculation methods differ regarding the used radionuclides, consumption rates and whether they use age specific dose conversion factors or not. In Germany administrative guidelines for the determination of the total indicative dose are still not available. As they have analyzed a large number of waters in the past, the authors derive a praxis orientated concept for the determination of the total indicative dose which respects radiological, analytical and hydrochemical aspects as well. Finally it is suggested to handle sparkling waters in the same manner as drinking waters. (orig.)

Multiple-dose pharmacokinetic study of proguanil and cycloguanil following 12-hourly administration of 100 mg proguanil hydrochloride.

Science.gov (United States)

Jamaludin, A; Mohamad, M; Navaratnam, V; Yeoh, P Y; Wernsdorfer, W H

1990-09-01

A pharmacokinetic study with 12-hourly doses of 100 mg proguanil hydrochloride over 15 days has been conducted in six adult male Malaysian volunteers. Steady state for proguanil was established after the fourth dose on Day 2, for the active metabolite cycloguanil as from Day 3 inclusive. The steady state mean peak concentration of proguanil was 1201.6 +/- 132.4 nmol/l, the mean trough concentration 650.0 +/- 58.1 nmol/l. The corresponding values for cycloguanil were 317.0 +/- 44.4 nmol/l (mean peak) and 230.8 +/- 35.1 nmol/l (mean trough). The profiles and peak/trough ratios of proguanil and cycloguanil with 12-hourly dosing offer better prospects for protection against malaria than those obtained with 24-hourly doses of 200 mg proguanil hydrochloride, the current routine in malaria chemoprophylaxis.

Effective method of continuous rocuronium administration based on effect-site concentrations using a pharmacokinetic/pharmacodynamic model during propofol-remifentanil anesthesia.

Science.gov (United States)

Moriyama, Takahiro; Matsunaga, Akira; Nagata, Osamu; Enohata, Kei; Kamikawaji, Tomomi; Uchino, Erika; Kanmura, Yuichi

2015-08-01

Rocuronium bromide (Rb) is a rapid onset, intermediate-acting neuromuscular blocking agent that is suitable for continuous administration. The appropriate rate of rocuronium administration is, however, difficult to determine due to large interindividual differences in sensitivity to rocuronium. The aim of this study was to clarify whether the simulated rocuronium concentration at the time of recovery to %T1 > 0 % after the initial administration of rocuronium is a good indicator of optimal effect-site concentrations during continuous rocuronium administration. Twenty-one patients were anesthetized with propofol. After induction, Rb 0.6 mg/kg was administered intravenously, and nerve stimulation using the single stimulation mode was conducted every 15 s. When %T1 recovered to >0 % after the initial administration of Rb, the effect-site concentration of rocuronium, calculated by pharmacokinetic simulation with Wierda's set of parameters, was recorded and defined as the recovery concentration (Rb r.c.). The administration rate of rocuronium was adjusted to maintain the Rb r.c. during surgery. Rb administration was discontinued just before the end of surgery, and the recovery time until %T1 > 25 % was recorded. Plasma Rb concentrations were measured at 1 and 3 h after the initiation of continuous Rb administration. The mean Rb r.c. was 1.56 ± 0.35 μg/ml, with minimum and maximum values of 1.09 and 2.08 μg/ml, respectively. The %T1 did not increase above 10 % in any of the patients during continuous administration of Rb, and the recovery period to %T1 > 25 % ranged from 9 to 29 min. The effect-site concentrations of Rb calculated with Wierda's parameters significantly correlated with plasma concentrations (P < 0.01) at both 1 and 3 h after the initial administration of Rb. The results suggest that our method may be one of the most reliable protocols for the continuous administration of Rb described to date for maintaining suitable muscle relaxation during surgery

Plasma paracetamol concentrations and pharmacokinetics following rectal administration in neonates and young infants

DEFF Research Database (Denmark)

Hansen, Tom Giedsing; O'Brien, K; Morton, N S

1999-01-01

Despite widespread use in children pharmacokinetic data about paracetamol are relatively scarce, not the least in the youngest age groups. This study aimed to describe plasma paracetamol concentrations and pharmacokinetics of a single rectal paracetamol dose in neonates and young infants....

Reduced glutathione concentration and glutathione reductase activity in various rat tissues after the administration of some radioprotective agents

International Nuclear Information System (INIS)

Pulpanova, J.; Kovarova, H.; Ledvina, M.

1982-01-01

The concentrations of reduced glutathione (GSH) and activity of glutathione reductase were investigated in rat liver, kidney and spleen after intraperitoneal administration of cystamine (50 mg/kg), mexamine (10 mg/kg), or a mixture of cystamine with mexamine (20 + 10 mg/kg). The GSH concentration increased after the administration of cystamine in the liver (maximum between the 20th and 30th min), in the kidney and spleen (maximum after 60 min). The cystamine + mexamine mixture also caused a significant increase of the GSH concentration in all the organs investigated; however, the values increased at earlier intervals as after the cystamine administration. No substantial effect was shown in the case of the mexamine administration, only 30 min after the administration the values were higher. The activity of glutathione reductase was significantly lower over the entire period examined. This was found in the liver and kidney as after the administration of cystamine, as after the radioprotective mixture. There was also a less pronounced inhibition of the enzyme activity in the spleen. Mexamine as a single radioprotector had practically no influence on the activity. (author)

Efficacy of high iodine concentration contrast medium with saline pushing in hepatic CT in patients with chronic liver disease. Comparison of high doses-standard contrast medium concentration

International Nuclear Information System (INIS)

Matoba, Munetaka; Kondo, Tamaki; Nishikawa, Takahiro; Kuginuki, Yasuaki; Yokota, Hajime; Higashi, Kotaro; Tonami, Hisao

2006-01-01

The aim of this study was to compare the enhancement of liver parenchyama with high iodine concentration contrast medium with saline pushing to that with high doses standard iodine concentration in hepatic CT in patients with chronic liver disease. There was no statistically significant difference regarding to the enhancement of liver parenchyama between the 370 mgI/ml of contrast medium with saline pushing and high doses standard iodine concentration contrast medium. (author)

Estimation of maximum credible atmospheric radioactivity concentrations and dose rates from nuclear tests

International Nuclear Information System (INIS)

Telegadas, K.

1979-01-01

A simple technique is presented for estimating maximum credible gross beta air concentrations from nuclear detonations in the atmosphere, based on aircraft sampling of radioactivity following each Chinese nuclear test from 1964 to 1976. The calculated concentration is a function of the total yield and fission yield, initial vertical radioactivity distribution, time after detonation, and rate of horizontal spread of the debris with time. calculated maximum credible concentrations are compared with the highest concentrations measured during aircraft sampling. The technique provides a reasonable estimate of maximum air concentrations from 1 to 10 days after a detonation. An estimate of the whole-body external gamma dose rate corresponding to the maximum credible gross beta concentration is also given. (author)

Dosing strategy based on prevailing aminoglycoside minimum inhibitory concentration in India: Evidence and issues

Directory of Open Access Journals (Sweden)

Balaji Veeraraghavan

2017-01-01

Full Text Available Aminoglycosides are important agents used for treating drug-resistant infections. The current dosing regimen of aminoglycosides does not achieve sufficient serum level concentration for the infected bacterial pathogen interpreted as susceptible based on laboratory testing. Minimum inhibitory concentration was determined for nearly 2000 isolates of Enterobacteriaceae and Pseudomonas aeruginosa by broth microdilution method. Results were interpreted based on CLSI and EUCAST interpretative criteria and the inconsistencies in the susceptibility profile were noted. This study provides insights into the inconsistencies existing in the laboratory interpretation and the corresponding clinical success rates. This urges the need for revising clinical breakpoints for amikacin, to resolve under dosing leading to clinical failure.

Radionuclide concentrations and dose assessment of cistern water and groundwater at the Marshall Islands

International Nuclear Information System (INIS)

Noshkin, V.E.; Eagle, R.J.; Wong, K.M.; Jokela, T.A.; Robison, W.L.

1981-01-01

A radiological survey was conducted from September through November of 1978 to determine the concentrations of radionuclides in the terrestrial and marine environments of 11 atolls and 2 islands in the Northern Marshall Islands. More than 70 cistern and groundwater samples were collected at the atolls; the volume of each sample was between 55 and 100 l. The concentration of 90 Sr in cistern water at most atolls is that expected from world-wide fallout in wet deposition. Except for Bikini and Rongelap, 137 Cs concentrations in cistern water are in agreement with the average predicted concentrations from wet deposition. The 239+240 Pu concentrations are everywhere less than the predicted fallout concentrations except at Rongelap, Ailinginae, and Bikini where the measured and predicted concentrations are in general agreement. During the period sampled, most groundwater concentrations of 90 Sr and 137 Cs were everywhere higher than the concentrations in cistern water. Concentrations of the transurancies in filtered groundwater solution were everywhere comparable to or less than the concentrations in cistern water. It is concluded that the concentrations of radionuclides detected during any single period may not necessarily reflect the long-term average concentrations or the concentrations that might be observed if a lined well were extended above the surface. In any case, at all atolls the 90 Sr and 137 Cs concentrations in groundwater are below the concentration guidelines for drinking water recommended by the Environmental Protection Agency. The maximum annual dose rates and the 30- and 50-y integral doses are calculated for the intake of both cistern water and groundwater for each of the atolls

Evaluation of annual effective dose from indoor radon concentration in Eastern Province, Dammam, Saudi Arabia

Science.gov (United States)

Abuelhia, E.

2017-11-01

The aim of this study is to determine the indoor radon concentration and to evaluate the annual effective dose received by the inhabitants in Dammam, Al-Khobar, and compare it with new premises built at university of dammam. The research has been carried out by using active detection method; Electronic Radon Detector (RAD-7) a solid state α-detector with its special accessories. The indoor radon concentration measured varies from 10.2 Bqm-3 to 25.8 Bqm-3 with an average value of 18.8 Bqm-3 and 19.7 Bqm-3 to 23.5 Bqm-3 with an average value of 21.7 Bqm-3, in Dammam and Al-khobar dwellings, respectively. In university of dammam the radon concentration varies from 7.4 Bqm-3 to 15.8 Bqm-3 with an average value of 9.02 Bqm-3. The values of annual effective doses were found to be 0.47mSv/y, 0.55mSv/y, and 0.23mSv/y, in Dammam, Al-khobar and university new premises, respectively. The average radon concentration in the old dwellings was two times compared to that in the new premises and it was 25.4 Bqm-3 lower than the world average value of 40 Bqm-3 reported by the UNSCEAR. The annual effective doses in the old dwellings was found to be (0.55mSv/y) two times the doses received at the new premises, and below the world wide average of 1.15mSv/y reported by ICRP (2010). The indoor radon concentration in the study region is safe as far as health hazard is concerned.

Sex-dependent behavioral changes in rat offspring after in utero administration of a single low dose PBDE 47

Energy Technology Data Exchange (ETDEWEB)

Kuriyama, S.N.; Talsness, C.E.; Chahoud, I. [Charite Univ. Medical School Berlin (Germany). Inst. of Clinical Pharmacology and Toxicology, Dept. Toxicology, Campus Benjamin Franklin

2004-09-15

Increasing levels of polybrominated diphenyl ethers (PBDEs) in environmental and human samples has resulted in intensive discussion regarding possible hazard identification and risk assessment in the last years. In rodents, exposure to PBDE mixtures or single congeners has resulted in a mixed induction of CYP450- dependent enzymes, showing increased activity of hepatic EROD and PROD. In addition, genotoxicity has been observed in recombination assays, and neurotoxicity has been reported in mice exposed during development. Acute and sub-chronic exposures of mice and rats to a PBDE mixture (DE-71) cause dose-dependent reductions in serum concentrations of thyroxin (T4), and stressinduced elevations in plasma corticosterone. Further, some hydroxylated metabolites of PBDE congeners exhibit a higher potency in vivo than T4 in competitive binding to human transthyretin (TTR), the transport protein mediating transfer of thyroid hormones across the placenta and into the brain. The available information in the literature clearly indicates that PBDEs are potent neurotoxicants, causing effects at doses lower than that able to disrupt thyroid hormone profiles and change CYP 450 activities. Neurobehavior effects, which includes defects in learning and memory, and changes in nicotinic receptors were found at doses starting at 0.45 ppm in mouse (9). The congeners, PBDE 47 and PBDE 99, have also been shown to cause permanent aberrations in spontaneous behavior in mice which was more pronounced with increasing age. PBDE 47 is the most predominant congener found in environmental and human samples, including human breast milk. Its presence in breast milk highlights the importance of evaluating possible effects following early developmental exposure and because this period represents a critical time which an organism is extremely susceptible to minor changes in hormonal milieu. Variances in terms of time point and concentration of exposure to steroids can lead to an organizational

Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs.

Science.gov (United States)

Laber, G

1988-03-01

Kinetic variables for tiamulin in the normal dog have been determined. Serum concentrations of tiamulin were compared after intramuscular (i.m.) and subcutaneous (s.c.) administration of a single dose of tiamulin. Following a single i.m. dose of 10 mg/kg body weight, the compound was calculated to have a Cmax = 0.61 +/- 0.15 micrograms/ml, a Tmax = 6 h and a t1/2 = 4.7 +/- 1.4 h. Tiamulin showed dose-dependent pharmacokinetics when given as a single s.c. dose of either 10 mg or 25 mg/kg body weight. For the lower dose, the values Cmax = 1.55 +/- 0.11 micrograms/ml, Tmax = 8 h and t1/2 = 4.28 +/- 0.18 h were obtained. For the higher dose Cmax = 3.14 +/- 0.04 micrograms/ml, Tmax = 8 h and t1/2 = 12.4 +/- 3.4 h were calculated. When tiamulin was administered subcutaneously at a dose rate of 10 mg/kg body weight, higher and better maintained serum levels were achieved than those following i.m. administration. After repeated s.c. doses no significant accumulation of tiamulin occurred. Assuming that a continuous effective serum concentration is necessary throughout the course of therapy, these data would indicate that tiamulin should be given every 24 h.

Effects of oral megestrol acetate administration on the hypothalamic-pituitary-adrenal axis of male bottlenose dolphins (Tursiops truncatus).

Science.gov (United States)

Houser, Dorian S; Champagne, Cory D; Jensen, Eric D; Smith, Cynthia R; Cotte, Lara S; Meegan, Jenny M; Booth, Rebecca K; Wasser, Samuel K

2017-07-15

OBJECTIVE To evaluate the impact of oral megestrol acetate (MA) administration on adrenal function in male bottlenose dolphins (Tursiops truncatus). DESIGN Serial cross-sectional study. ANIMALS 8 adult male dolphins, all of which were receiving MA at various daily doses (range, 0 to 60 mg, PO) for the control of reproductive behavior. PROCEDURES Blood samples were collected every 2 weeks for 1 year from dolphins trained to voluntarily provide them. Cortisol, ACTH, and other hormone concentrations were measured in serum or plasma via radioimmunoassay or ELISA. Fecal samples, also provided by dolphins voluntarily, were assayed for glucocorticoid metabolite concentrations. Effects of daily MA dose on hormone concentrations were evaluated. RESULTS Daily MA doses as low as 10 mg strongly suppressed cortisol secretion in nearly all dolphins, and except for a single measurement, no dolphin had measurable serum concentrations at doses ≥ 20 mg. Variations in serum cortisol concentration were unrelated to season but were directly related to ACTH concentrations, suggesting primary effects upstream of the adrenal gland. Cessation of MA administration resulted in almost immediate restoration of measurable serum cortisol concentrations, although concentrations continued to rise in a few dolphins over the following weeks to months. CONCLUSIONS AND CLINICAL RELEVANCE Caution should be exercised when administering MA to control reproductive behavior in male dolphins. Because the hypothalamic-pituitary-adrenal axis appeared to be sensitive to even small doses of MA in dolphins, duration of treatment may be the most critical consideration.

Ocular pharmacokinetics of besifloxacin following topical administration to rabbits, monkeys, and humans.

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Proksch, Joel W; Granvil, Camille P; Siou-Mermet, Raphaële; Comstock, Timothy L; Paterno, Michael R; Ward, Keith W

2009-08-01

Studies were conducted to evaluate the ocular penetration and systemic exposure to besifloxacin, a fluoroquinolone antibiotic, following topical ocular administration to animals and humans. Besifloxacin ophthalmic suspension (0.6%) was administered as a topical ocular instillation to pigmented rabbits, cynomolgus monkeys, and human subjects. At predetermined intervals after dosing, samples of ocular tissues and plasma were collected and analyzed for besifloxacin levels using HPLC/MS/MS methods. Besifloxacin demonstrated good ocular penetration in rabbits and monkeys, with rapid absorption and sustained concentrations observed in anterior ocular tissues through 24 h after a single administration. Maximum besifloxacin concentrations in conjunctiva, cornea, and aqueous humor of monkeys were 6.43 microg/g, 2.10 microg/g, and 0.796 microg/mL, respectively, after a single topical dose, and concentrations declined in these tissues with an apparent half-life of 5-14 h. Following a single topical ocular administration to humans, the maximum besifloxacin concentration in tears was 610 microg/g with concentrations decreasing to approximately 1.6 microg/g at 24 h. The resulting pharmacokinetic parameters for besifloxacin in human tears were evaluated relative to the MIC(90) values (microg/mL) for besifloxacin against Streptococcus pneumoniae (0.125), Staphylococcus aureus (0.25), Staphylococcus epidermidis (0.5), and Haemophilus influenzae (0.06). Following a single topical administration, the C(max)/MIC(90) ratios for besifloxacin in human tears were > or =1,220, and the AUC((0-24))/MIC(90) ratios were > or =2,500 for these relevant ocular pathogens. Following repeated 3-times daily (TID) topical ocular administration to human subjects with clinically diagnosed bacterial conjunctivitis, maximum besifloxacin concentrations in plasma were less than 0.5 ng/mL, on average. Taken together, the results of the current investigation provide a PK/PD-based rationale that supports the

Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid.

Science.gov (United States)

Flanagan, Shawn; Fang, Edward; Muñoz, Kelly A; Minassian, Sonia L; Prokocimer, Philippe G

2014-09-01

Tedizolid phosphate is a novel antibacterial under investigation for the treatment of gram-positive infections. This study was conducted to assess the pharmacokinetics, safety, and tolerability of intravenous tedizolid phosphate as well as the oral bioavailability of tedizolid phosphate. Double-blind, single-ascending dose, multiple-dose pharmacokinetics study, as well as tolerability and open-label crossover studies. Single center in the United States (Covance Clinical Research Unit, Madison, WI) between September 2009 and January 2010. Ninety healthy volunteers. Single intravenous (IV) doses of tedizolid phosphate 50 mg (lead-in) and 100-400 mg. Single oral and IV dose of tedizolid phosphate 200 mg in crossover fashion. Multiple IV doses of tedizolid phosphate 200 and 300 mg for up to 7 days. A dose-dependent increase was observed in the maximum plasma concentration (1.2-5.1 μg/ml) and the area under the concentration-time curve (17.4-58.7 μg × hr/ml) of tedizolid (the microbiologically active moiety of tedizolid phosphate) after single IV doses of tedizolid phosphate 100-400 mg. Administration of IV tedizolid phosphate 200 mg once/day for 7 days resulted in minimal (28%) tedizolid accumulation. The absolute oral bioavailability of tedizolid after a single 200-mg dose of tedizolid phosphate was 91%; pharmacokinetic parameters of tedizolid were similar with oral and IV administration. Treatment-related adverse events occurred in 41% of subjects. Most adverse events were related to infusion site and became more frequent with multiple dosing. In an additional 3-day tolerability study, IV tedizolid phosphate 200 mg and placebo were similarly tolerated, based on visual infusion phlebitis scores. These results from a population of healthy volunteers support once/day dosing of tedizolid phosphate 200 mg with both the oral and IV formulations, without the need for dose adjustment when switching administration routes. © 2014 Cubist Pharmaceuticals. Pharmacotherapy

A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.

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Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F; Hamaoka, Takafumi

2015-06-25

Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.

Dose- and time-dependent pharmacokinetics of apigenin trimethyl ether.

Science.gov (United States)

Elhennawy, Mai Gamal; Lin, Hai-Shu

2018-06-15

Apigenin trimethyl ether (5,7,4'-trimethoxyflavone, ATE), one of the key polymethoxyflavones present in black ginger (rhizome of Kaempferia parviflora) possesses various health-promoting activities. To optimize its medicinal application, the pharmacokinetics of ATE was assessed in Sprague-Dawley rats with emphases to identify the impacts from dose and repeated dosing on its major pharmacokinetic parameters. Plasma ATE levels were monitored by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Upon single intravenous administration (2 mg/kg), plasma levels of ATE declined through an apparent first-order process while dose-escalation to 4 and 8 mg/kg led to its non-linear disposition, which could be described by the Michaelis-Menten model. Similarly, dose-dependent oral pharmacokinetics was confirmed and when the dose was escalated from 5 to 15 and 45 mg/kg, much longer mean residence time (MRT 0→last ), higher dose-normalized maximal plasma concentration (C max /Dose) and exposure (AUC/Dose) were observed at 15 and/or 45 mg/kg. One-week daily oral administration of ATE at 15 mg/kg caused its accelerated elimination and the plasma exposure (AUC) after intravenous (2 mg/kg) and oral administration (15 mg/kg) dropped ~40 and 60%, respectively. As ATE displayed both dose- and time-dependent pharmacokinetics, caution is needed in the medicinal applications of ATE and/or black ginger. Copyright © 2018 Elsevier B.V. All rights reserved.

Guaifenesin Pharmacokinetics Following Single‐Dose Oral Administration in Children Aged 2 to 17 Years

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Thompson, Gary A.; Solomon, Gail; Albrecht, Helmut H.; Reitberg, Donald P.

2016-01-01

Abstract This study characterized guaifenesin pharmacokinetics in children aged 2 to 17 years (n = 40) who received a single oral dose of guaifenesin (age‐based doses of 100‐400 mg) 2 hours after breakfast. Plasma samples were obtained before and for 8 hours after dosing and analyzed for guaifenesin using liquid chromatography‐tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods, relationships with age were assessed using linear regression, and dose proportionality was assessed on 95% confidence intervals. Based on the upper dose recommended in the monograph (for both children and adolescents), area under the curve from time zero to infinity and maximum plasma concentration both increased with age. However, when comparing the upper dose for children aged 2 to 11 years with the lower dose for adolescents aged 12 to 17 years, similar systemic exposure was observed. As expected due to increasing body size, oral clearance (CLo) and terminal volume of distribution (Vz/F) increased with age. Due to a larger increase in Vz/F than CLo, an increase in terminal exponential half‐life was also observed. Allometric scaling indicated no maturation‐related changes in CLo and Vz/F. PMID:26632082

Doses for various pathways to man based on unit concentrations of radionuclides pertinent to decontamination and decommissioning of properties

International Nuclear Information System (INIS)

Hill, G.S.

1979-03-01

This report gives dose tabulations for unit concentrations of radionuclides likely to be encountered in the decommissioning of real estate contaminated with uranium and thorium ores and residues. The reported doses may be ratioed to known air, soil, and water concentrations, exposure times, and intakes to estimate the total radiation dose for individuals exposed to the facilities. These dose estimates may be used in developing criteria to determine appropriate remedial actions for returning the properties to useful purposes and for establishing restrictions for such use

Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation.

Science.gov (United States)

Frank, N; Hermida, P; Sanchez-Londoño, A; Singh, R; Gradil, C M; Uricchio, C K

2017-07-01

Octreotide is a somatostatin analog that suppresses insulin secretion. We hypothesized that octreotide would suppress insulin concentrations in horses and that normal (N) horses and those with insulin dysregulation (ID) would differ significantly in their plasma glucose and insulin responses to administration of octreotide. Twelve horses, N = 5, ID = 7. Prospective study. An oral sugar test was performed to assign horses to N and ID groups. Octreotide (1.0 μg/kg IV) was then administered, and blood was collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, 75, and 90 minute, and 2, 3, 4, 6, 8, 12, and 24 hour for measurement of glucose and insulin concentrations. Area under the curve (AUC) values were calculated. Mean AUC values for glucose and insulin did not differ between normal (n = 5) and ID (n = 7) groups after octreotide injection. Significant time (P glucose and insulin concentrations. A group × time interaction (P = .091) was detected for insulin concentrations after administration of octreotide, but the group (P = .33) effect was not significant. Octreotide suppresses insulin secretion, resulting in hyperglycemia, and then concentrations increase above baseline as glycemic control is restored. Our hypothesis that octreotide causes insulin concentrations to decrease in horses was supported, but differences between N and ID groups did not reach statistical significance when blood glucose and insulin responses were compared. The utility of an octreotide response test remains to be determined. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Pharmacokinetics of meropenem after intravenous, intramuscular and subcutaneous administration to cats.

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Albarellos, Gabriela A; Montoya, Laura; Passini, Sabrina M; Lupi, Martín P; Lorenzini, Paula M; Landoni, María F

2016-12-01

The aim of the study was to describe the pharmacokinetics and predicted efficacy of meropenem after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration to cats at a single dose of 10 mg/kg. Five adult healthy cats were used. Blood samples were withdrawn at predetermined times over a 12 h period. Meropenem concentrations were determined by microbiological assay. Pharmacokinetic analyses were performed with computer software. Initial estimates were determined using the residual method and refitted by non-linear regression. The time that plasma concentrations were greater than the minimum inhibitory concentration (T >MIC) was estimated by applying bibliographic MIC values and meropenem MIC breakpoint. Maximum plasma concentrations of meropenem were 101.02 µg/ml (C p(0) , IV), 27.21 µg/ml (C max , IM) and 15.57 µg/ml (C max , SC). Bioavailability was 99.69% (IM) and 96.52 % (SC). Elimination half-lives for the IV, IM and SC administration were 1.35, 2.10 and 2.26 h, respectively. Meropenem, when administered to cats at a dose of 10 mg/kg q12h,, is effective against bacteria with MIC values of 6 μg/ml, 7 μg/ml and 10 μg/ml for IV, IM and SC administration, respectively. However, clinical trials are necessary to confirm clinical efficacy of the proposed dosage regimen. © The Author(s) 2015.

Effect of propranolol in head tremor: quantitative study following single-dose and sustained drug administration.

Science.gov (United States)

Calzetti, S; Sasso, E; Negrotti, A; Baratti, M; Fava, R

1992-12-01

The effect of the beta-adrenoceptor antagonist propranolol has been investigated in nine patients suffering from isolated (six patients) or prominent (three patients) essential tremor of the head. In a double-blind, placebo-controlled study the tremorolytic efficacy of propranolol has been assessed by a quantitative accelerometric method after a single oral dose (120 mg) and following 2 weeks of sustained treatment with two different dosage regimens of the drug (120 and 240 mg daily). As compared with placebo, a significant reduction in tremor magnitude was found following a single oral dose but not on sustained administration of the beta-blocker at either dosage. The results suggest that the efficacy of sustained propranolol on isolated or prominent essential head tremor is less predictable and satisfactory than expected on the basis of the single-dose response, as compared with hand tremor.

Pharmacokinetics of ceftiofur sodium after intramuscular or subcutaneous administration in green iguanas (Iguana iguana).

Science.gov (United States)

Benson, Keith G; Tell, Lisa A; Young, Lee A; Wetzlich, Scott; Craigmill, Arthur L

2003-10-01

To determine the pharmacokinetics of ceftiofur sodium after IM and SC administration in green iguanas. 6 male and 4 female adult green iguanas. In a crossover design, 5 iguanas received a single dose of ceftiofur sodium (5 mg/kg) IM, and 5 iguanas received the same dose SC. Blood samples were taken at 0, 20, and 40 minutes and 1, 2, 4, 8, 24, 48, and 72 hours after administration. After a 10-week washout period, each iguana was given the same dose via the reciprocal administration route, and blood was collected in the same fashion. Ceftiofur free-acid equivalents were measured via high-performance liquid chromatography. The first phase intercepts were significantly different between the 2 administration routes. Mean maximum plasma concentration was significantly higher with the IM (28.6 +/- 8.0 microg/mL) than the SC (18.6 +/- 8.3 microg/mL) administration route. There were no significant differences between terminal half-lives (harmonic mean via IM route, 15.7 +/- 4.7 hours; harmonic mean via SC route, 19.7 +/- 6.7 hours) and mean areas under the curve measured to the last time point (IM route, 11,722 +/- 7,907 microg x h/mL; SC route, 12,143 +/- 9,633 microg x h/mL). Ceftiofur free-acid equivalent concentrations were maintained > or = 2 microg/mL for > 24 hours via both routes. A suggested dosing schedule for ceftiofur sodium in green iguanas for microbes susceptible at > 2 microg/mL would be 5 mg/kg, IM or SC, every 24 hours.

Nonrandomized study comparing the effects of preoperative radiotherapy and daily administration of low-dose cisplatin with those radiotherapy alone for oral cancer

International Nuclear Information System (INIS)

Kurita, Hiroshi; Azegami, Takuya; Kobayashi, Hirokazu; Kurashina, Kenji; Tanaka, Kouichi; Kotani, Akira; Oguchi, Masahiko; Tamura, Minoru.

1997-01-01

The purpose of this study was to compare the effect of preoperative radiotherapy and daily administration of low-dose cisplatin with those of radiotherapy alone for oral cancer. Ten patients underwent preoperative radiotherapy of 30 to 40 Gy with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten patients received external radiotherapy alone. The locoregional response rates (complete response and partial response) did not differ significantly between the two groups (80% for combined therapy and 60% for radiotherapy alone). On histopathologic evaluation of surgical specimens, however, the combined-therapy group (80%) had a higher response rate than did the radiotherapy-alone group (10%; p<0.01). We conclude that daily administration of low-dose cisplatin enhances the efficacy of radiotherapy against primary tumors. We also suggested that combined therapy may be beneficial as an initial treatment for oral cancer before a planned operation. (author)

Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a meta-analysis

Directory of Open Access Journals (Sweden)

Oliveira João

2010-09-01

Full Text Available Abstract Background The effects of gonadotrophin-releasing hormone agonist (GnRH-a administered in the luteal phase remains controversial. This meta-analysis aimed to evaluate the effect of the administration of a single-dose of GnRH-a in the luteal phase on ICSI clinical outcomes. Methods The research strategy included the online search of databases. Only randomized studies were included. The outcomes analyzed were implantation rate, clinical pregnancy rate (CPR per transfer and ongoing pregnancy rate. The fixed effects model was used for odds ratio. In all trials, a single dose of GnRH-a was administered at day 5/6 after ICSI procedures. Results All cycles presented statistically significantly higher rates of implantation (P Conclusions These findings demonstrate that the luteal-phase single-dose GnRH-a administration can increase implantation rate in all cycles and CPR per transfer and ongoing pregnancy rate in cycles with GnRH antagonist ovarian stimulation protocol. Nevertheless, by considering the heterogeneity between the trials, it seems premature to recommend the use of GnRH-a in the luteal phase. Additional randomized controlled trials are necessary before evidence-based recommendations can be provided.

Radon concentration, absorbed dose rate in air and concentration of natural radionuclides in soil in the Osaka district of Japan

International Nuclear Information System (INIS)

Megumi, K.; Matsunami, T.; Ishiyama, T.; Abe, M.; Kimura, S.; Yamazaki, K.; Tsujimoto, T.

1992-01-01

Radon concentrations in outdoor air at 18 sites in the Osaka district, in the central part of Japan's main island, were measured with electrostatic integrating radon monitors which were developed by Y Ikebe et al of the Osaka survey centre as part of a nationwide survey of radon indoors and outdoors in Japan conducted by the National Institute of Radiological Science. The mean radon concentration in outdoor air during 2-month periods was measured over a period of a year and a half. In addition, the absorbed dose rate in air and the concentration of natural radionuclides in soil were measured at 40 sites in Osaka Prefecture which is located in the central part of the Osaka district using thermoluminescence dosemeters and with gamma ray spectrometry, respectively. Radon concentration in outdoor air showed a seasonal pattern, reaching its maximum during the winter and its minimum during the summer, but this variation was not significant at the coastal sites. It was concluded that this variation is correlated with a seasonal wind which blows from the continental interior to the ocean in winter and in the opposite direction in summer, as well as with geographical factors. Radon concentration in outdoor air in the Osaka district ranged from 0.6 to 17.9 Bq.m -3 and mean annual radon concentration in outdoor air at the 18 sites ranged from 2.7 to 6.9 Bq.m -3 . It was discovered that radon concentration in outdoor air decreased with wind speed in both winter and summer. The absorbed dose rate in air ranged from 66 to 114 nGy.h -1 , and the concentration of 226 Ra in soil ranged from 20 to 60 Bq.kg -1 respectively. (author)

Pharmacokinetics of repeated oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Souza, Marcy J; Gerhardt, Lillian; Cox, Sherry

2013-07-01

To determine the pharmacokinetics of tramadol hydrochloride (30 mg/kg) following twice-daily oral administration in Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots. Tramadol hydrochloride was administered to each parrot at a dosage of 30 mg/kg, PO, every 12 hours for 5 days. Blood samples were collected just prior to dose 2 on the first day of administration (day 1) and 5 minutes before and 10, 20, 30, 60, 90, 180, 360, and 720 minutes after the morning dose was given on day 5. Plasma was harvested from blood samples and analyzed by high-performance liquid chromatography. Degree of sedation was evaluated in each parrot throughout the study. No changes in the parrots' behavior were observed. Twelve hours after the first dose was administered, mean ± SD concentrations of tramadol and its only active metabolite M1 (O-desmethyltramadol) were 53 ± 57 ng/mL and 6 ± 6 ng/mL, respectively. At steady state following 4.5 days of twice-daily administration, the mean half-lives for plasma tramadol and M1 concentrations were 2.92 ± 0.78 hours and 2.14 ± 0.07 hours, respectively. On day 5 of tramadol administration, plasma concentrations remained in the therapeutic range for approximately 6 hours. Other tramadol metabolites (M2, M4, and M5) were also present. On the basis of these results and modeling of the data, tramadol at a dosage of 30 mg/kg, PO, will likely need to be administered every 6 to 8 hours to maintain therapeutic plasma concentrations in Hispaniolan Amazon parrots.

Absorption kinetics and steady-state plasma concentrations of theophylline following therapeutic doses of two sustained-release preparations

DEFF Research Database (Denmark)

Andersen, O; Nielsen, M K; Eriksen, P B

1983-01-01

Ten healthy volunteers received two sustained-release preparations as a single and multiple dose regimen in an open crossover study. Plasma theophylline concentrations were measured by an enzyme immunoassay. The limited fluctuation of the theophylline levels at steady state, with twice daily...... formulation, whereas this was not the case for the other (r = 0.27 and 0.49). The daily dose necessary to keep the plasma concentration within the therapeutic range of 55-110 mumole/liter varied from 7.9 to 22.9 mg/kg. Only mild side effects were recorded, but they were not correlated to the plasma...... theophylline concentration....

Patch test concentrations (doses in mg/cm2 ) for the 12 non-mix fragrance substances regulated by European legislation.

Science.gov (United States)

Bruze, Magnus; Svedman, Cecilia; Andersen, Klaus Ejner; Bruynzeel, Derk; Goossens, An; Johansen, Jeanne Duus; Matura, Mihaly; Orton, David; Vigan, Martine

2012-03-01

According to EU legislation, 26 fragrance substance allergens must be labelled on cosmetic products. For 12 of them, the optimal patch test concentration/dose has not been evaluated. To establish the optimal patch test doses in mg/cm2 for the 12 fragrance substances that are not included in fragrance mix I or II in the European baseline patch test series. Patch testing with the 12 fragrance substances was performed in a stepwise manner encompassing up to five rounds in at least 100 dermatitis patients for each round. Before patch testing, an individual maximum concentration/dose was determined for each fragrance substance. The predetermined maximum patch test concentrations/doses could be tested for all 12 fragrance substances, with no observable adverse reactions being noted. For each fragrance substance investigated, it is recommended that half of the maximum patch test dose (mg/cm2) be used for aimed and screening patch testing. © 2012 John Wiley & Sons A/S.

Single point estimation of phenytoin dosing: a reappraisal.

Science.gov (United States)

Koup, J R; Gibaldi, M; Godolphin, W

1981-11-01

A previously proposed method for estimation of phenytoin dosing requirement using a single serum sample obtained 24 hours after intravenous loading dose (18 mg/Kg) has been re-evaluated. Using more realistic values for the volume of distribution of phenytoin (0.4 to 1.2 L/Kg), simulations indicate that the proposed method will fail to consistently predict dosage requirements. Additional simulations indicate that two samples obtained during the 24 hour interval following the iv loading dose could be used to more reliably predict phenytoin dose requirement. Because of the nonlinear relationship which exists between phenytoin dose administration rate (RO) and the mean steady state serum concentration (CSS), small errors in prediction of the required RO result in much larger errors in CSS.

Evaluation of the concentration of marbofloxacin in alveolar macrophages and pulmonary epithelial lining fluid after administration in dogs.

Science.gov (United States)

Boothe, Harry W; Jones, Sarah A; Wilkie, W Scott; Boeckh, Albert; Stenstrom, Kristol K; Boothe, Dawn M

2005-10-01

To determine concentrations of marbofloxacin in alveolar macrophages (AMs) and epithelial lining fluid (ELF) and compare those concentrations with plasma concentrations in healthy dogs. 12 adult mixed-breed and purebred hounds. 10 dogs received orally administered marbofloxacin at a dosage of 2.75 mg/kg every 24 hours for 5 days. Two dogs served as nontreated controls. Fiberoptic bronchoscopy and bronchoalveolar lavage procedures were performed while dogs were anesthetized with propofol, approximately 6 hours after the fifth dose. The concentrations of marbofloxacin in plasma and bronchoalveolar fluid (cell and supernatant fractions) were determined by use of high-performance liquid chromatography with detection of fluorescence. Mean +/- SD plasma marbofloxacin concentrations 2 and 6 hours after the fifth dose were 2.36 +/- 0.52 microg/mL and 1.81 +/- 0.21 microg/mL, respectively. Mean +/- SD marbofloxacin concentration 6 hours after the fifth dose in AMs (37.43 +/- 24.61 microg/mL) was significantly greater than that in plasma (1.81 +/- 0.21 microg/mL) and ELF (0.82 +/- 0.34 microg/mL), resulting in a mean AM concentration-to-plasma concentration ratio of 20.4, a mean AM:ELF ratio of 60.8, and a mean ELF-to-plasma ratio of 0.46. Marbofloxacin was not detected in any samples from control dogs. Marbofloxacin concentrations in AMs were greater than the mean inhibitory concentrations of major bacterial pathogens in dogs. Results indicated that marbofloxacin accumulates in AMs at concentrations exceeding those reached in plasma and ELF The accumulation of marbofloxacin in AMs may facilitate treatment for susceptible intracellular pathogens or infections associated with pulmonary macrophage infiltration.

Pharmacokinetics and brain distribution of tetrahydropalmatine and tetrahydroberberine after oral administration of DA-9701, a new botanical gastroprokinetic agent, in rats.

Science.gov (United States)

Jung, Ji Won; Kwon, Yong Sam; Jeong, Jin Seok; Son, Miwon; Kang, Hee Eun

2015-01-01

DA-9701, a new botanical gastroprokinetic agent, has potential for the management of delayed gastric emptying in Parkinson's disease if it has no central anti-dopaminergic activity. Therefore, we examined the pharmacokinetics of DA-9701 components having dopamine D2 receptor antagonizing activity, tetrahydropalmatine (THP) and tetrahydroberberine (THB), following various oral doses (80-328 mg/kg) of DA-9701. The distribution of THP and THB to the brain and/or other tissues was also evaluated after single or multiple oral administrations of DA-9701. Oral administration of DA-9701 yielded dose-proportional area under the plasma concentration-time curve (AUC0-8 h) and maximum plasma concentration (Cmax) values for THP and THB, indicating linear pharmacokinetics (except for THB at the lowest dose). THP and THB's large tissue-to-plasma concentration ratios indicated considerable tissue distribution. High concentrations of THP and THB in the stomach and small intestine suggest an explanation for DA-9701's potent gastroprokinetic activity. The maximum concentrations of THP and THB in brain following multiple oral DA-9701 for 7 d (150 mg/kg/d) was observed at 30 min after the last oral DA-9701 treatment: 131±67.7 ng/g for THP and 6.97±4.03 ng/g for THB. Although both THP and THB pass through the blood-brain barrier, as indicated by brain-to-plasma concentration ratios greater than unity (approximately 2-4), oral administration of DA-9701 at the effective dose in humans is not expected to lead to sufficient brain concentrations to exert central dopamine D2 receptor antagonism.

Pharmacokinetics of penciclovir after oral administration of its prodrug famciclovir to horses.

Science.gov (United States)

Tsujimura, Koji; Yamada, Masayuki; Nagata, Shun-ichi; Yamanaka, Takashi; Nemoto, Manabu; Kondo, Takashi; Kurosawa, Masahiko; Matsumura, Tomio

2010-03-01

We investigated the pharmacokinetics of penciclovir after oral administration of its prodrug famciclovir to horses. Following an oral dose of famciclovir at 20 mg/kg, maximum plasma concentrations of penciclovir occurred between 0.75 and 1.5 hr (mean 0.94 + or - 0.38 hr) after dosing and were in the range 2.22 to 3.56 microg/ml (mean 2.87 + or - 0.61 microg/ml). The concentrations of penciclovir declined in a biphasic manner after the peak concentration was attained. The mean half-life of the rapid elimination phase was 1.73 + or - 0.34 hr whereas that of the slow elimination phase was 34.34 + or - 13.93 hr. These pharmacokinetic profiles observed were similar to those of another antiherpesvirus drug, acyclovir, previously reported in horses following oral dosing of its prodrug valacyclovir.

Measurement of radiocesium concentration in trees using cumulative gamma radiation dose rate detection systems - A simple presumption for radiocesium concentration in living woods using glass-badge based gamma radiation dose rate detection system

Energy Technology Data Exchange (ETDEWEB)

Yoshihara, T.; Hashida, S.N. [Plant Molecular Biology, Laboratory of Environmental Science, Central Research Institute of Electric Power Industry (CRIEPI), 1646 Abiko, Chiba 270-1194 (Japan); Kawachi, N.; Suzui, N.; Yin, Y.G.; Fujimaki, S. [Radiotracer Imaging Gr., Quantum Beam Science Center, Japan Atomic Energy Agency (JAEA), 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan); Nagao, Y.; Yamaguchi, M. [Takasaki Advanced Radiation Research Institute, Japan Atomic Energy Agency (JAEA), 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan)

2014-07-01

Radiocesium from the severe accident at the Fukushima Dai-ichi Nuclear Power Plant on 11 March 2011 contaminates large areas. After this, a doubt for forest products, especially of mushroom, is indelible at the areas. Pruned woody parts and litters are containing a considerable amount of radiocesium, and generates a problem at incineration and composting. These mean that more attentive survey for each subject is expected; however, the present survey system is highly laborious/expensive and/or non-effective for this purpose. On the other hand, we can see a glass-badge based gamma radiation dose rate detection system. This system always utilized to detect a personal cumulative radiation dose, and thus, it is not suitable to separate a radiation from a specific object. However, if we can separate a radiation from a specific object and relate it with the own radiocesium concentration, it would enable us to presume the specific concentration with just an easy monitoring but without a destruction of the target nature and a complicated process including sampling, pre-treatment, and detection. Here, we present the concept of the measurement and results of the trials. First, we set glass-badges (type FS, Chiyoda Technol Corp., Japan) on a part of bough (approximately 10 cm in diameter) of Japanese flowering cherry trees (Prunus x yedoensis cv. Somei-Yoshino) with four different settings: A, a direct setting without any shield; B, a setting with an aluminum shield between bough and the glass-badge; C, a setting with a lead shield between bough and the glass-badge; D, a setting with a lead shield covering the glass-badge to shut the radiation from the surrounding but from bough. The deduction between the amount of each setting should separate a specific radiation of the bough from unlimited radiation from the surrounding. Even if the hourly dose rate is not enough to count the difference, a moderate cumulative dose would clear the difference. In fact, results demonstrated a

Impact of high- versus low-dose neuromuscular blocking agent administration on unplanned 30-day readmission rates in retroperitoneal laparoscopic surgery.

Directory of Open Access Journals (Sweden)

Martijn Boon

Full Text Available Recent data shows that a neuromuscular block (NMB induced by administration of high doses of rocuronium improves surgical conditions in certain procedures. However, there are limited data on the effect such practices on postoperative outcomes. We performed a retrospective analysis to compare unplanned 30-day readmissions in patients that received high-dose versus low-dose rocuronium administration during general anesthesia for laparoscopic retroperitoneal surgery. This retrospective cohort study was performed in the Netherlands in an academic hospital where routine high-dose rocuronium NMB has been practiced since July 2015. Charts of patients receiving anesthesia between January 2014 and December 2016 were searched for surgical cases receiving high-dose rocuronium and matched with respect to procedure, age, sex and ASA classification to patients receiving low-dose rocuronium. The primary post-operative outcome was unplanned 30-day readmission rate. There were 130 patients in each cohort. Patients in the high- and low-dose rocuronium cohorts received 217 ± 49 versus 37 ± 5 mg rocuronium, respectively. In the high-dose rocuronium group neuromuscular activity was consistently monitored; matched patients were unreliably monitored. All patients receiving high-dose rocuronium were reversed with sugammadex, while just 33% of matched patients were reversed with sugammadex and 20% with neostigmine; the remaining patients were not reversed. Unplanned 30-day readmission rate was significantly lower in the high-dose compared to the low-dose rocuronium cohort (3.8% vs. 12.7%; p = 0.03; odds ratio = 0.33, 95% C.I. 0.12-0.95. This small retrospective study demonstrates a lower incidence of unplanned readmissions within 30-days following laparoscopic retroperitoneal surgery with high-dose relaxant anesthesia and sugammadex reversal in comparison to low-dose relaxant anesthesia. Further prospective studies are needed in larger samples to corroborate our

Impact of high- versus low-dose neuromuscular blocking agent administration on unplanned 30-day readmission rates in retroperitoneal laparoscopic surgery.

Science.gov (United States)

Boon, Martijn; Martini, Chris; Yang, H Keri; Sen, Shuvayu S; Bevers, Rob; Warlé, Michiel; Aarts, Leon; Niesters, Marieke; Dahan, Albert

2018-01-01

Recent data shows that a neuromuscular block (NMB) induced by administration of high doses of rocuronium improves surgical conditions in certain procedures. However, there are limited data on the effect such practices on postoperative outcomes. We performed a retrospective analysis to compare unplanned 30-day readmissions in patients that received high-dose versus low-dose rocuronium administration during general anesthesia for laparoscopic retroperitoneal surgery. This retrospective cohort study was performed in the Netherlands in an academic hospital where routine high-dose rocuronium NMB has been practiced since July 2015. Charts of patients receiving anesthesia between January 2014 and December 2016 were searched for surgical cases receiving high-dose rocuronium and matched with respect to procedure, age, sex and ASA classification to patients receiving low-dose rocuronium. The primary post-operative outcome was unplanned 30-day readmission rate. There were 130 patients in each cohort. Patients in the high- and low-dose rocuronium cohorts received 217 ± 49 versus 37 ± 5 mg rocuronium, respectively. In the high-dose rocuronium group neuromuscular activity was consistently monitored; matched patients were unreliably monitored. All patients receiving high-dose rocuronium were reversed with sugammadex, while just 33% of matched patients were reversed with sugammadex and 20% with neostigmine; the remaining patients were not reversed. Unplanned 30-day readmission rate was significantly lower in the high-dose compared to the low-dose rocuronium cohort (3.8% vs. 12.7%; p = 0.03; odds ratio = 0.33, 95% C.I. 0.12-0.95). This small retrospective study demonstrates a lower incidence of unplanned readmissions within 30-days following laparoscopic retroperitoneal surgery with high-dose relaxant anesthesia and sugammadex reversal in comparison to low-dose relaxant anesthesia. Further prospective studies are needed in larger samples to corroborate our findings and

[Influence of dose regimen on gentamycin nephrotoxicity in rats].

Science.gov (United States)

Oliveira, V C; Tejos, C R; Hosaka, E M; Andrade, S C; Araújo, M; Vattimo, M F

2001-06-01

The acute renal failure (ARF), that still presents a right mortality rate (50%) can be defined as an abrupt decline of the glomerular filtration, resultant of ischemic or toxicity event. The drugs nephrotoxicity is one of the most frequent cause (27%) of ARF and it is suggested that the interval of administration of the drug can interfere in this side effect, however the best administration regimen is not very well established. This study evaluated the renal function of rats that received gentamicin (100 mg/kg) in one dose or in two doses (2 x 50 mg/kg), by intraperitoneal infusion. The results obtained in this research, indicated that the single infusion of gentamicin determined smaller nephrotoxicity by the reduction of serum concentration of this drug in 24 hours, decreasing the intracellular accumulation of this gentamicin, which is one of the main cellular mechanisms of this renal injury. The single dose treatment regime, otherwise, shows advantages not only related to the nephrotoxicity effect, but also it is relevant to the cost and safety, which can be rationable factors in the administration of this drug.

Immunotoxicity of perfluorinated alkylates: calculation of benchmark doses based on serum concentrations in children

DEFF Research Database (Denmark)

Grandjean, Philippe; Budtz-Joergensen, Esben

2013-01-01

BACKGROUND: Immune suppression may be a critical effect associated with exposure to perfluorinated compounds (PFCs), as indicated by recent data on vaccine antibody responses in children. Therefore, this information may be crucial when deciding on exposure limits. METHODS: Results obtained from...... follow-up of a Faroese birth cohort were used. Serum-PFC concentrations were measured at age 5 years, and serum antibody concentrations against tetanus and diphtheria toxoids were obtained at ages 7 years. Benchmark dose results were calculated in terms of serum concentrations for 431 children...

Dose-response regressions for algal growth and similar continuous endpoints: Calculation of effective concentrations

DEFF Research Database (Denmark)

Christensen, Erik R.; Kusk, Kresten Ole; Nyholm, Niels

2009-01-01

We derive equations for the effective concentration giving 10% inhibition (EC10) with 95% confidence limits for probit (log-normal), Weibull, and logistic dose -responsemodels on the basis of experimentally derived median effective concentrations (EC50s) and the curve slope at the central point (50......% inhibition). For illustration, data from closed, freshwater algal assays are analyzed using the green alga Pseudokirchneriella subcapitata with growth rate as the response parameter. Dose-response regressions for four test chemicals (tetraethylammonium bromide, musculamine, benzonitrile, and 4...... regression program with variance weighting and proper inverse estimation. The Weibull model provides the best fit to the data for all four chemicals. Predicted EC10s (95% confidence limits) from our derived equations are quite accurate; for example, with 4-4-(trifluoromethyl)phenoxy-phenol and the probit...

Evaluation of occupational radiation dose in nuclear medicine: radiopharmaceutical administration to scintiscanning exams of myocardial perfusion; Avaliacao da dose de radiacao ocupacional em medicina nuclear: administracao de radiofarmacos em exames de cintilografria de perfusao miocardica

Energy Technology Data Exchange (ETDEWEB)

Komatsu, Cassio V., E-mail: cassiok@yahoo.com [Medicina Nuclear do Triangulo (MNT), Uberlandia, MG (Brazil); Michelin, Charlie A.; Jakubiak, Rosangela R., E-mail: charlie@utfpr.edu.br, E-mail: requi@utfpr.edu.br [Universidade Tecnologica Federal do Parana (UTFPR), Curitiba, PR (Brazil); Lemes, Alyne O.; Silva, Juliana L.M., E-mail: alyne275@gmail.com, E-mail: jujumontesdocinho@gmail.com [Faculdade do Trabalho (FATRA), Uberlandia, MG (Brazil)

2013-11-01

In nuclear medicine, workers directly involved in exams are constantly exposed to ionizing radiation. The procedure for administration of the radiopharmaceutical to the patient is one of the most critical times of exposure. In tests of myocardial perfusion scintigraphy (MPS) administration of radiopharmaceutical repeats the steps of rest and cardiac stress. In this study, we used a Geiger -Mueller detector for measuring occupational radiation doses for during the administration of technetium- {sup 99m}- sestamibi in MPS tests. In the evaluation, discriminated the stages of examination and related professional experience time to doses measures at home. It were followed 110 procedures at home (55 conducted by professionals with over 5 years experience and 55 conducted by professionals with less than 1 year of experience) and 55 effort procedures. The results showed that the rest of the procedure time and dose are related to the experience of the worker. More experienced workers were faster (mean: 43 {+-} 16 vs 67 {+-} 25 seconds / procedure), and therefore received lower doses (mean 0.57 {+-} 0.16 versus 0.80 {+-} 0.24 {mu}Sv / procedure), both with statistical significance (p <0.001). In step effort, there were procedures lasting longer (mean: 19 {+-} 2 minutes / procedure), which resulted in higher doses (mean 3.0 {+-} 0.6 {mu}Sv / procedure)

Measurement of the radon concentration in an underground public facility and dose assessment. Fukuoka Tenjin Shopping Center

International Nuclear Information System (INIS)

Narazaki, Yukinori; Tokonami, Shinji; Sanada, Tetsuya; Kanno, Nobuyuki; Yamada, Yuji

2000-01-01

Radon concentrations were measured with a passive radon detector from April 1998 through June 1999 in the Fukuoka Tenjin Underground Shopping Center to assess the dose affecting workers because of radon progeny inhalation. The radon concentration during the period was distributed from a range of 1.9 to 13.6 Bq/m 3 . The arithmetic average concentration was estimated to be 6.9±2.4 Bq/ 3 . The radon level was lower than that in dwellings in Japan and other countries. No spatial distribution of radon concentration was found in that area. From continuous measurement, the radon concentration was found to be high from midnight to noon and low in the afternoon. Little difference was noted between the daily average radon concentration and that during working hours. There was no seasonal variation. The equilibrium factor of 0.21±0.10 was obtained during working hours. The activity-weighted size distribution of radon progeny was evaluated by using the number distribution of ambient aerosols and the classical attachment theory. Consequently, the activity median diameter was 150 nm. The unattached fraction of radon progeny was estimated to be 0.025 with an empirical equation. The annual effective dose of workers at the Tenjin center was calculated with the dose conversion factor from the UNSCEAR 1993 report and estimated to be 0.024 mSv/y. (author)

Estimation of absorbed doses in humans due to intravenous administration of fluorine-18-fluorodeoxyglucose in PET studies

International Nuclear Information System (INIS)

Mejia, A.A.; Nakamura, T.; Masatoshi, I.; Hatazawa, J.; Masaki, M.; Watanuki, S.

1991-01-01

Radiation absorbed doses due to intravenous administration of fluorine-18-fluorodeoxyglucose in positron emission tomography (PET) studies were estimated in normal volunteers. The time-activity curves were obtained for seven human organs (brain, heart, kidney, liver, lung, pancreas, and spleen) by using dynamic PET scans and for bladder content by using a single detector. These time-activity curves were used for the calculation of the cumulative activity in these organs. Absorbed doses were calculated by the MIRD method using the absorbed dose per unit of cumulated activity, 'S' value, transformed for the Japanese physique and the organ masses of the Japanese reference man. The bladder wall and the heart were the organs receiving higher doses of 1.2 x 10(-1) and 4.5 x 10(-2) mGy/MBq, respectively. The brain received a dose of 2.9 x 10(-2) mGy/MBq, and other organs received doses between 1.0 x 10(-2) and 3.0 x 10(-2) mGy/MBq. The effective dose equivalent was estimated to be 2.4 x 10(-2) mSv/MBq. These results were comparable to values of absorbed doses reported by other authors on the radiation dosimetry of this radiopharmaceutical

Urinary profile of methylprednisolone and its metabolites after oral and topical administrations.

Science.gov (United States)

Matabosch, Xavier; Pozo, Oscar J; Monfort, Núria; Pérez-Mañá, Clara; Farré, Magi; Marcos, Josep; Segura, Jordi; Ventura, Rosa

2013-11-01

Methylprednisolone (MP) is prohibited in sports competitions when administered by systemic routes; however its use by topical administration is allowed. Therefore, analytical approaches to distinguish between these different administration pathways are required. A reporting level of 30ng/mL was established for this purpose. However, the suitability of that reporting level for MP is not known. In the present work, excretion profiles of MP and different metabolites after oral and topical administrations have been compared. A method for the quantification of MP and the qualitative detection of fifteen previously reported metabolites has been validated. The method involved an enzymatic hydrolysis, liquid-liquid extraction and analysis by liquid chromatography coupled to tandem mass spectrometry. The method was found to be linear, selective, precise and accurate. The high sensitivity (limit of detection 0.1ng/mL) and linear range (0.1-250ng/mL) achieved allowed for the quantification of MP at both the low concentrations present after topical administration and the high concentrations detected after oral intake. The method was applied to samples collected after oral (4 or 40mg) and topical administration (10mg of MP aceponate/day for 5 consecutive days) to healthy volunteers. After oral administration, MP and all metabolites were detected in urines collected up to at least 36h. Only MP and five metabolites were detected in samples obtained after topical treatment. As expected, concentrations of MP after topical administration were well below current reporting level (30ng/mL), however 3 out of 4 samples in range 8-24h after the low oral dose (4mg) were also below that concentration. Taking into account metabolites detected after both administration routes, metabolites 16β,17α,21-trihydroxy-6α-methylpregna-1,4-diene-3,11,20-trione (M8) and 17α,20α,21-trihydroxy-6α-methylpregna-1,4-diene-3,11-dione (M11) are best markers to differentiate between topical and oral

Age- and sex-specific estimation of dose to a normal thyroid from clinical administration of iodine-131

International Nuclear Information System (INIS)

Killough, G.G.; Eckerman, K.F.

1986-09-01

This report describes the derivation of an age- and sex-dependent model of radioiodine dosimetry in the thyroid and the application of the model to estimating the thyroid dose for each of 4215 patients who were exposed to 131 I in diagnostic and therapeutic procedures. In most cases, the data available consisted of the patient's age at the time of administration, the patient's sex, the quantity of activity administered, the clinically determined uptake of radioiodine by the thyroid, and the time after administration at which the uptake was determined. The model was made to conform to these data requirements by the use of age-specific estimates of the biological half-time of iodine in the thyroid and an age- and sex-dependent representation of the mass of the thyroid. Also, it was assumed that the thyroid burden was maximum at 24 hours after administration (the 131 I dose is not critically sensitive to this assumption). The metabolic model is of the form A(t) = K x (exp(-μ 1 t) - exp(-μ 2 t)) μCi where μ/sub i/ = λ/sub r/ + λ/sub i//sup b/ (i = 1, 2), λ/sub r/ is the radiological decay-rate coefficient, and the λ/sub i//sup b/ are biological removal-rate coefficients. The values of λ/sub i//sup b/ are determined by solving a nonlinear equation that depends on assumptions about the time of maximum uptake and the eventual biological loss rate (through which age dependence enters). An addendum (Appendix C) extends the method to other radioiodines and gives age- and sex-dependent dose conversion factors for most isotopes

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.

Plasma disposition, concentration in the hair, and anthelmintic efficacy of eprinomectin after topical administration in donkeys.

Science.gov (United States)

Gokbulut, Cengiz; Di Loria, Antonio; Gunay, Necati; Masucci, Roberto; Veneziano, Vincenzo

2011-12-01

To investigate plasma disposition, concentration in the hair, and anthelmintic efficacy of eprinomectin after topical administration in donkeys. 12 donkeys naturally infected with strongyle nematodes. The pour-on formulation of eprinomectin approved for use in cattle was administered topically to donkeys at a dosage of 0.5 mg/kg. Heparinized blood samples and hair samples were collected at various times between 1 hour and 40 days after administration. Samples were analyzed via high-performance liquid chromatography with fluorescence detection. Fecal strongyle egg counts were performed by use of a modified McMaster technique before and at weekly intervals for 8 weeks after treatment. Plasma concentration and systemic availability of eprinomectin were relatively higher in donkeys, compared with values reported for other animal species. Concerning the anthelmintic efficacy against strongyle nematodes, eprinomectin was completely effective (100%) on days 7 and 14 and highly effective (> 99%) until the end of the study at 56 days after treatment. No abnormal clinical signs or adverse reactions were observed for any donkeys after treatment. Eprinomectin had excellent safety. The relatively high plasma concentration after topical administration could result in use of eprinomectin for the control and treatment of parasitic diseases in donkeys.

Oromucosal Administration of Interferon to Humans

Directory of Open Access Journals (Sweden)

Manfred W. Beilharz

2010-01-01

Full Text Available The prevailing dogma is that, to be systemically effective, interferon-alpha (IFNα must be administered in sufficiently high doses to yield functional blood concentrations. Such an approach to IFNa therapy has proven effective in some instances, but high-dose parenteral IFNα therapy has the disadvantage of causing significant adverse events. Mounting evidence suggests that IFNα delivered into the oral cavity in low doses interacts with the oral mucosa in a unique manner to induce systemic host defense mechanisms without IFNα actually entering the circulation, thus reducing the potential for toxic side effects. A better understanding of the applications and potential benefits of this treatment modality are under active investigation. This paper provides a review of the relevant literature on the clinical use of the oromucosal route of administration of interferon, with an emphasis on the treatment of influenza.

Effect of administration route and dose of streptavidin or biotin on the tumor uptake of radioactivity in intraperitoneal tumor with multistep targeting

International Nuclear Information System (INIS)

Zhang Meili; Yao Zhengsheng; Sakahara, Harumi; Saga, Tsuneo; Nakamoto, Yuji; Sato, Noriko; Zhao Songji; Nakada, Hiroshi; Yamashina, Ikuo; Konishi, Junji

1998-01-01

The effect of the administration route and dose of streptavidin or biotin on the biodistribution of radioactivity in multistep targeting was studied in nude mice bearing intraperitoneal (IP) colon cancer xenograft. The multistep targeting included a two-step method using biotinylated antibody and radiolabeled streptavidin and a three-step method with radiolabeled biotin based on the two-step method. A monoclonal antibody, MLS128, which recognizes Tn antigen on mucin, was biotinylated and injected intravenously (IV) or IP in nude mice bearing human colon cancer LS180 IP xenografts for pretargeting. In the two-step method, IP-injected streptavidin showed a higher tumor uptake and tumor-to-nontumor ratios than IV-injected streptavidin regardless of administration route of pretargeting. The tumor uptake of radiolabeled streptavidin was increased with a high dose of biotinylated antibody pretargeting, but decreased with an increasing dose of streptavidin. In the three-step targeting, IP injection also gave a higher tumor uptake of radiolabeled biotin than IV injection. In conclusion, IP administration of radiolabeled streptavidin or biotin resulted in more efficient IP tumor targeting with the multistep methods

Effect of donepezil hydrochloride (E2020) on basal concentration of extracellular acetylcholine in the hippocampus of rats.

Science.gov (United States)

Kosasa, T; Kuriya, Y; Matsui, K; Yamanishi, Y

1999-09-10

The effects of oral administration of the centrally acting acetylcholinesterase (AChE) inhibitors, donepezil hydrochloride (donepezil: E2020: (+/-)-2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxy-indan-1-one monohydrochloride), tacrine (9-amino-1,2,3,4-tetrahydroacridine hydrochloride) and ENA-713 (rivastigmine: (S)-N-ethyl-3-[(1-dimethyl-amino)ethyl]-N-methyl-phenylcarbamate hydrogentartrate), which have been developed for the treatment of Alzheimer's disease, on the extracellular acetylcholine concentration in the hippocampus of rats were evaluated by using a microdialysis technique without adding cholinesterase inhibitor to the perfusion solution. We also compared the inhibition of brain AChE and the brain concentrations of these drugs. Donepezil at 2.5 mg/kg and tacrine at 5 mg/kg showed significant effects for more than 6 h. At these doses, the maximum increases were observed at about 1.5 h after administration of donepezil, and at about 2 h with tacrine, and were 499% and 422% of the pre-level, respectively. ENA-713 produced significant effects at doses of 0.625, 1.25 and 2.5 mg/kg, which lasted for about 1, 2 and 4 h, respectively. The maximum increases produced by these doses at about 0.5 h after administration were 190, 346 and 458% of the pre-level, respectively. The time courses of brain AChE inhibition with donepezil at 2.5 mg/kg, tacrine at 10 mg/kg and ENA-713 at 2.5 mg/kg were mirror images of the extracellular acetylcholine-increasing action at the same doses. The time courses of the brain concentrations of drugs after oral administration of donepezil at 2.5 mg/kg and tacrine at 10 mg/kg were consistent with those of brain AChE inhibition at the same doses, and there was a linear relation between these parameters. Brain concentration of ENA-713 at 2.5 mg/kg was below the limit of quantification at all time points measured. These results suggest that oral administration of donepezil, tacrine and ENA-713 increases acetylcholine concentration in the

Increased serum bile acid concentration following low-dose chronic administration of thioacetamide in rats, as evidenced by metabolomic analysis

Energy Technology Data Exchange (ETDEWEB)

Jeong, Eun Sook; Kim, Gabin; Shin, Ho Jung [Department of Pharmacology and Pharmacogenomics Research Center, Inje University, College of Medicine, Bokjiro 75, Busanjin-Gu, Busan 614-735 (Korea, Republic of); Park, Se-Myo; Oh, Jung-Hwa; Kim, Yong-Bum; Moon, Kyoung-Sik [Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-343 (Korea, Republic of); Choi, Hyung-Kyoon [College of Pharmacy, Chung-Ang University, Seoul (Korea, Republic of); Jeong, Jayoung [Ministry of Food and Drug Safety, Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do 361-951 (Korea, Republic of); Shin, Jae-Gook [Department of Pharmacology and Pharmacogenomics Research Center, Inje University, College of Medicine, Bokjiro 75, Busanjin-Gu, Busan 614-735 (Korea, Republic of); Kim, Dong Hyun, E-mail: dhkim@inje.ac.kr [Department of Pharmacology and Pharmacogenomics Research Center, Inje University, College of Medicine, Bokjiro 75, Busanjin-Gu, Busan 614-735 (Korea, Republic of)

2015-10-15

A liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS)-based metabolomics approach was employed to identify endogenous metabolites as potential biomarkers for thioacetamide (TAA)-induced liver injury. TAA (10 and 30 mg/kg), a well-known hepatotoxic agent, was administered daily to male Sprague–Dawley (SD) rats for 28 days. We then conducted untargeted analyses of endogenous serum and liver metabolites. Partial least squares discriminant analysis (PLS-DA) was performed on serum and liver samples to evaluate metabolites associated with TAA-induced perturbation. TAA administration resulted in altered levels of bile acids, acyl carnitines, and phospholipids in serum and in the liver. We subsequently demonstrated and confirmed the occurrence of compromised bile acid homeostasis. TAA treatment significantly increased serum levels of conjugated bile acids in a dose-dependent manner, which correlated well with toxicity. However, hepatic levels of these metabolites were not substantially changed. Gene expression profiling showed that the hepatic mRNA levels of Ntcp, Bsep, and Oatp1b2 were significantly suppressed, whereas those of basolateral Mrp3 and Mrp4 were increased. Decreased levels of Ntcp, Oatp1b2, and Ostα proteins in the liver were confirmed by western blot analysis. These results suggest that serum bile acids might be increased due to the inhibition of bile acid enterohepatic circulation rather than increased endogenous bile acid synthesis. Moreover, serum bile acids are a good indicator of TAA-induced hepatotoxicity. - Highlights: • Endogenous metabolic profiles were assessed in rat after treatment of thioacetamide. • It significantly increased the levels of bile acids in serum but not in the liver. • Expression of the genes related to bile acid secretion and reuptake was decreased. • Increased serum bile acids result from block of enterohepatic circulation of bile acids.

Increased serum bile acid concentration following low-dose chronic administration of thioacetamide in rats, as evidenced by metabolomic analysis

International Nuclear Information System (INIS)

Jeong, Eun Sook; Kim, Gabin; Shin, Ho Jung; Park, Se-Myo; Oh, Jung-Hwa; Kim, Yong-Bum; Moon, Kyoung-Sik; Choi, Hyung-Kyoon; Jeong, Jayoung; Shin, Jae-Gook; Kim, Dong Hyun

2015-01-01

A liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS)-based metabolomics approach was employed to identify endogenous metabolites as potential biomarkers for thioacetamide (TAA)-induced liver injury. TAA (10 and 30 mg/kg), a well-known hepatotoxic agent, was administered daily to male Sprague–Dawley (SD) rats for 28 days. We then conducted untargeted analyses of endogenous serum and liver metabolites. Partial least squares discriminant analysis (PLS-DA) was performed on serum and liver samples to evaluate metabolites associated with TAA-induced perturbation. TAA administration resulted in altered levels of bile acids, acyl carnitines, and phospholipids in serum and in the liver. We subsequently demonstrated and confirmed the occurrence of compromised bile acid homeostasis. TAA treatment significantly increased serum levels of conjugated bile acids in a dose-dependent manner, which correlated well with toxicity. However, hepatic levels of these metabolites were not substantially changed. Gene expression profiling showed that the hepatic mRNA levels of Ntcp, Bsep, and Oatp1b2 were significantly suppressed, whereas those of basolateral Mrp3 and Mrp4 were increased. Decreased levels of Ntcp, Oatp1b2, and Ostα proteins in the liver were confirmed by western blot analysis. These results suggest that serum bile acids might be increased due to the inhibition of bile acid enterohepatic circulation rather than increased endogenous bile acid synthesis. Moreover, serum bile acids are a good indicator of TAA-induced hepatotoxicity. - Highlights: • Endogenous metabolic profiles were assessed in rat after treatment of thioacetamide. • It significantly increased the levels of bile acids in serum but not in the liver. • Expression of the genes related to bile acid secretion and reuptake was decreased. • Increased serum bile acids result from block of enterohepatic circulation of bile acids.

[Interaction between fluorine and zinc after long-term oral administration into the digestive system of rats].

Science.gov (United States)

Mazurek-Mochol, Małgorzata

2002-01-01

Drug interactions are the side effect of administration of two or more drugs or a drug-food combination. Although some drug interactions are intentional and beneficial to the patient, the majority are unintentional and associated with a potentially harmful effect. The aim of this study was to search for interactions in rats between fluoride and zinc administered orally for 12 weeks and to elucidate any potential toxicological and therapeutic consequences. 60 male Wistar rats were divided into six groups of ten rats each and exposed to: 1. controls (distilled water); 2. sodium fluoride (NaF); 3. low-dose zinc (Zn); 4. high-dose zinc; 5. NaF + low-dose Zn; 6. NaF + high-dose Zn. At the end of the experiment the content of F- and Zn+ in serum, urine, incisors, femur and mandible was measured and densitometry of femoral bones was performed. Serum alkaline phosphatase, alanine and aspartate aminotransferase activities, as well as bilirubin and creatinine concentrations were determined to confirm non-toxicity of fluoride dose. Animals receiving NaF only demonstrated higher content of fluorine in serum, urine bones and teeth. Zinc concentrations in serum, urine, bones and teeth were elevated in rats receiving zinc with or without NaF. Fluorine accumulation in bones and teeth was reduced by Zn, but in general the effect lacked statistical significance. Zinc slightly reduced the concentrations of fluorine in serum and urine. Sodium fluoride slightly reduced the concentration of zinc in serum and urine. Bone mineral content (BMC) was significantly increased by NaF and was not further increased by co-administration of zinc. No changes in serum alkaline phosphatase, alanine and aspartate aminotransferase activities, bilirubin and creatinine concentrations were detected. In conclusion, simultaneous administration of fluorine and zinc may be beneficial for prevention and treatment of pathologic conditions in bones and teeth and is not accompanied by an increase in fluorine

Effects of dose, species, and dosing vehicle on the disposition of methacrylonitrile (MAN) in male rats

International Nuclear Information System (INIS)

Sanchez, I.M.; Ghanayem, B.I.

1991-01-01

MAN is structurally similar to known carcinogen acrylontrile (AN), with nitriles having similar industrial uses. Current studies were designed to investigate the biological fate of 2- 14 C-MAN in rats. After gavage administration of 115, 11.5 or 1.15 mg MAN/kg in water, F344 male rats were placed in glass metabolism cages and urine, expired air and feces were collected. Rats were sacrificed at various times and concentration of MAN-derived radioactivity in tissues was determined. MAN was rapidly absorbed from the GI tract and distributed to all major tissues. Sixty-70% of the low and medium doses were exhaled as 14 CO 2 in 72 hr compared to 25% of the highest dose. While 40% of the highest dose was expired as organic volatiles in 72 hr, only 9-12% of the low and accounted for 20-30% of all doses within 72 hr after dosing. Comparison of MAN disposition in Sprague-Dawley (SD) and F344 rats at 115 mg/kg revealed that SD rats excreted a greater % of the dose as 14 CO 2 and in the urine than did F344 rats. Administration of 115 mg MAN/kg to SD male rats in safflower oil resulted in increased elimination of MAN-derived radioactivity as CO 2 , volatiles, and in the urine over that observed when administered in water. These results suggest that: (1) saturation of MAN metabolism occurs at high doses: (2) MAN metabolism and disposition differ with the strain of rats studied; (3) MAN disposition may vary with the dosing vehicle used; and (4) MAN metabolism and disposition is apparently different from that reported on AN

Treating tuberculosis with high doses of anti-TB drugs: mechanisms and outcomes.

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Xu, Yuhui; Wu, Jianan; Liao, Sha; Sun, Zhaogang

2017-10-03

Tuberculosis (TB) is considered as one of the most serious threats to public health in many parts of the world. The threat is even more severe in the developing countries where there is a lack of advanced medical amenities and contemporary anti-TB drugs. In such situations, dosage optimization of existing medication regimens seems to be the only viable option. Therapeutic drug monitoring study results suggest that high-dose treatment regimens can compensate the low serum concentration of anti-TB drugs and shorten the therapy duration. The article presents a critical review on the possible changes that occur in the host and the pathogen upon the administration of standard and high-dose regimens. Some of the most common factors that are responsible for low anti-TB drug concentrations in the serum are differences in hosts' body weight, metabolic processing of the drug, malabsorption and/or drug-drug interaction. Furthermore, failure to reach the cavitary pulmonary and extrapulmonary tissues also contributes to the therapeutic inefficiency of the drugs. In such conditions, administration of higher doses can help in compensating the pathogenic outcomes of enhancement of the pathogen's physical barriers, efflux pumps and genetic mutations. The present article also presents a summary of the recorded treatment outcomes of clinical trials that were conducted to test the efficacy of administration of high dose of anti-tuberculosis drugs. This review will help physicians across the globe to understand the underlying pathophysiological changes (including side effects) that dictate the clinical outcomes in patients administered with standard and/or high dose anti-TB drugs.

The relationship between tacrolimus concentration-dose ratio and genetic polymorphism in patients subjected to renal transplantation

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Rančić Nemanja

2018-01-01

Full Text Available Background/Aim. Tacrolimus concentration-dose ratio as a potential therapeutic drug monitoring strategy was suggested to be used for the patients subjected to renal transplantation. The aim of this study was examining the relationship between tacrolimus concentration-dose ratio, suggested to be used as a therapeutic drug monitoring strategy and the polymorphisms of genes encoding the most important enzymes, such as CYP3A5 and CYP3A4, as well as the transporter P-glycoprotein, for its metabolism and elimination. Methods. The study was designed as a prospective case series study, in which the unit of monitoring was the outpatient examination of 54 patients subjected to renal transplantation. Genotyping was performed by 7500 Real- Time PCR System by assessing allelic discrimination based on TaqMan® methodology. Results. Patients (n = 13 who were treated with less than 2 mg of tacrolimus/day (0.024 ± 0.006 mg/kg/day had the tacrolimus concentration-dose ratio larger than 150 ng/mL/mg/kg. In this group, 84.62% patients had CYP3А5 *3*3 allele. All of these patients had CYP3А4 *1*1/*1*1B allele. Regarding ABCB1 C3435T gene, 30.77% of patients had the TT gene variant, while 69.23% of our patients had CC and CT gene variants. Conclusion. Tacrolimus concentration-dose ratio greater than 150 ng/mL/mg/kg is cut-off value in patients subjected to renal transplantation which might point to patients who are poor CYP3A5 metabolizers and/or with dysfunctional P-glycoprotein.

Pharmacokinetics of [3H]levamisole in pigs after oral and intramuscular administration

International Nuclear Information System (INIS)

Galtier, P.; Escoula, L.; Alvinerie, M.

1983-01-01

A single oral (10 mg/kg of body weight) or IM (7.5 mg/kg) dose of [ 3 H]levamisole was administered to pigs. Liquid scintillation counting and high performance liquid chromatography were used to determine total radioactivity and drug levels in plasma, duodenal and cecal contents, bile, and urine for 24 and 72 hours after dosing. Pharmacokinetic analysis indicated a 1-compartment open model with higher plasma bioavailability of levamisole after IM injection. Biological half-lives for elimination of the drug were 9.3 and 6.9 hours after oral and IM administration, respectively. Anthelmintic concentrations were higher in intestinal contents after oral gavage than after IM injection. The drug appeared extensively metabolized in all body fluids and particularly in bile, regardless of the route of administration. Biliary excretion of radioactivity and unchanged levamisole represented only slight percentages of the administered dose (approx 0.4% and 4.2%, respectively, in 72 hours). In contrast, about 60% and 20% of the dose were eliminated via urine as tritiated materials and unchanged drug. The choice of the most efficacious route of administration is discussed in regard to localization of helminthic disease

Pharmacokinetics of imipenem after intravenous, intramuscular and subcutaneous administration to cats.

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Albarellos, Gabriela A; Denamiel, Graciela A; Montoya, Laura; Quaine, Pamela C; Lupi, Martín P; Landoni, María F

2013-06-01

The study describes the pharmacokinetics and predicted efficacy of imipenem after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration to five adult cats at a dose of 5 mg/kg. Susceptibility to imipenem [minimum inhibitory concentration (MIC)] was determined for antimicrobial resistant Escherichia coli (n = 13) and staphylococci (n = 3) isolated from domestic cat infections (urinary system, skin and conjunctiva). Maximum plasma concentrations of imipenem were 13.45 µg/ml (IV), 6.47 µg/ml (IM) and 3.83 µg/ml (SC). Bioavailability was 93.18% (IM) and 107.90% (SC). Elimination half-lives for IV, IM and SC administration were 1.17, 1.44 and 1.55 h, respectively. All tested bacteria were susceptible to imipenem; MIC values were 0.03 µg/ml for Staphylococcus species and imipenem concentrations remained above a MIC of 0.5 µg/ml for approximately 4 h (IV and IM) and 9 h (SC). Imipenem would be predicted to be effective for the treatment of antimicrobial resistant bacterial infections in cats at a dosage of 5 mg/kg every 6-8 h (IV, IM), or longer for the SC route. However, clinical trials are mandatory to establish its efficacy and proper dosing.

Hydrocortisone infusion exerts dose- and sex-dependent effects on attention to emotional stimuli.

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Breitberg, Alaina; Drevets, Wayne C; Wood, Suzanne E; Mah, Linda; Schulkin, Jay; Sahakian, Barbara J; Erickson, Kristine

2013-03-01

Glucocorticoid administration has been shown to exert complex effects on cognitive and emotional processing. In the current study we investigated the effects of glucocorticoid administration on attention towards emotional words, using an Affective Go/No-go task on which healthy humans have shown an attentional bias towards positive as compared to negative words. Healthy volunteers received placebo and either low-dose (0.15mg/kg) or high-dose (0.45mg/kg) hydrocortisone intravenously during two separate visits in a double-blind, randomized design. Seventy-five minutes post-infusion, the subjects performed tests of attention (Rapid Visual Information Processing [RVIP]), spatial working memory (Spatial Span) and emotional processing (Affective Go/No-go task [AGNG]). On the attention task, performance was impaired under both hydrocortisone doses relative to placebo, though the effect on error rate was not significant after controlling for age; Spatial Span performance was unaffected by hydrocortisone administration. On the AGNG task, relative to the placebo condition the low-dose hydrocortisone infusion decreased response time to emotional words while high-dose hydrocortisone increased response time. In the females specifically, both high and low dose hydrocortisone administration attenuated the normal attentional bias toward positively valenced words. These data suggest that, in healthy women, the modulation of attention by the emotional salience of stimuli is influenced by glucocorticoid hormone concentrations. Copyright © 2012 Elsevier Inc. All rights reserved.

Therapeutic efficacy and safety of various botulinum toxin A doses and concentrations in spastic foot after stroke: a randomized controlled trial

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Jiang Li

2017-01-01

Full Text Available No recommended guidelines currently exist for the therapeutic concentration or dose of botulinum toxin type A (BTXA injected into the muscle to treat limb spasticity. Therefore, in this randomized controlled trial, we explored the safety and efficacy of two concentrations and two doses of BTXA in the treatment of spastic foot after stroke to optimize this treatment in these patients. Eligible patients (n = 104 were randomized into four groups. The triceps surae and tibialis posterior on the affected side were injected with BTXA at one of two doses (200 U or 400 U and two concentrations (50 U/mL or 100 U/mL. The following assessments were conducted before as well as 4 days and 1, 2, 4, and 12 weeks after treatment: spasticity, assessed using the modified Ashworth scale; basic functional mobility, assessed using a timed up and go test; pace, assessed using a 10-meter timed walking test; and the ability to walk, assessed using Holden's graded scale and a visual analog scale. The reported results are based on the 89 patients that completed the study. We found significant differences for the two doses and concentrations of BTXA to improve the ability of patients to walk independently, with the high-dose/low-concentration combination providing the best effect. Onset and duration of the ameliorating effects of BTXA were 4–7 days and 12 weeks, respectively. Thus, BTXA effectively treated foot spasms after stroke at an optimal dose of 400 U and concentration of 50 U/mL.

The nucleic acid metabolism in rat liver after single and long-term administration of tritium oxide

International Nuclear Information System (INIS)

Shorokhova, V.B.

1984-01-01

It was shown that after a single administration of tritiUm oxide in a dose of 22.2 MBq/g body mass the liver mass increased, the concentration of nucleic acids decreased and the biosynthesjs rate increased dUring a one-month observation. By the end of the observation period (the first year) the parameters under study were normalized. The long-term administration of tritium oxide in daily doses of 0.37, 0.925 and 1.85 MBq/g body mass caused changes in the nucleac acid metabolism which were less manifest (at early times), than in the case of a single injection. At the same time, the long-term administration of tritium oxide in the dose of 0.925 MBq/g caused a substantial disturbance of the nucleic acid metabolism at later times (after 2-9 months)

The Effect of Nicotine Administration on Physical and Psychological Signs of Withdrawal Syndrome Induced by Single or Frequent Doses of Morphine in Rats

OpenAIRE

Mohammad Allahtavakoli; Fatemeh Amin; Elham Hakimizadeh; Ali Roohbakhsh; Sayed Ali Haeri Rohani; Ahmad Taghavi Rafsanjani; Abbas Haghparast; Ali Shamsizadeh

2012-01-01

Introduction. Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Materials and methods. Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later t...

Estimation of the optimal dosing regimen of escitalopram in dogs: A dose occupancy study with [11C]DASB.

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Olivia Taylor

Full Text Available Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day and a subsequent i.v. injection 0.83 mg/kg. Blood samples were taken up to 12 hours after i.v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended.

Estimation of the optimal dosing regimen of escitalopram in dogs: A dose occupancy study with [11C]DASB.

Science.gov (United States)

Taylor, Olivia; Van Laeken, Nick; Polis, Ingeborgh; Dockx, Robrecht; Vlerick, Lise; Dobbeleir, Andre; Goethals, Ingeborg; Saunders, Jimmy; Sadones, Nele; Baeken, Chris; De Vos, Filip; Peremans, Kathelijne

2017-01-01

Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day) and a subsequent i.v. injection 0.83 mg/kg. Blood samples were taken up to 12 hours after i.v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended.

Determination of 210Po concentration in commercially available infant formulae and assessment of daily ingestion dose

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Ravi K. Prabhath

2015-07-01

Full Text Available A study has been conducted to estimate the concentration of natural radioactive polonium in commercially available packaged infant food formulae available in Mumbai, India and the corresponding daily dose normalized based on its shelf life. Eleven most popular international brands of infant formulae were sourced from market and three aliquots from each sample were analysed for concordant results. Autodeposition method onto a silver planchet from hot dilute acid solution followed by alpha spectrometry was performed for estimation of polonium. Radiochemical recovery was ascertained by the addition of 209Po tracer. Radiochemical recovery of 209Po tracer was ranged from 14.7 to 98.1 %. The 210Po concentration in the samples was in the range of 0.08–0.23 Bq kg−1 on measured date and the corresponding daily dose, calculated on normalized date which is at mid-point of the shelf life of the sample, was ranged from 0.04 to 0.89 μSv d−1 as per the recommended daily consumption. The annual committed effective dose estimated based on the average of daily dose was found to be 150 μSv.

Concentration of total proteins in blood plasma of chickens hatched from irradiated eggs with low dose gamma radiation

International Nuclear Information System (INIS)

Vilic, M.; Kraljevic, P.; Miljanic, S.; Simpraga, M.

2005-01-01

It is known that low-dose ionising radiation may have stimulating effects on chickens. Low doses may also cause changes in the concentration of blood plasma total proteins, glucose and cholesterol in chickens. This study investigates the effects of low dose gamma-radiation on the concentration of total proteins in the blood plasma of chickens hatched from eggs irradiated with a dose of 0.15 Gy on incubation days 7 and 19. Results were compared with the control group (chickens hatched from non-irradiated eggs). After hatching, all other conditions were the same for both groups. Blood samples were drawn from the heart, and later from the wing vein on days 1, 3, 5, 7,10, 20, 30 and 42. The concentration of total proteins was determined spectrophotometrically using Boehringer Mannheim GmbH optimised kits. The concentration of total proteins in blood plasma in chickens hatched from eggs irradiated with 0.15 Gy on incubation day 7 showed a statistically significant decrease on the sampling day 3 (P less than 0.05) and 7 (P less than 0.01). The concentration of total proteins in blood plasma in chickens hatched from eggs irradiated with 0.15 Gy on incubation day 19 showed a statistically significant increase only on sampling day 1 (P less than 0.05). These results suggest that exposure of eggs to 0.15 Gy of gamma-radiation on the 7th and 19th day of incubation could produce different effects on the protein metabolism in chickens.(author)

Hormones of thyroid gland in sera of rats treated with different dose of concentrated potassium iodine solutions

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Marković Ljiljana

2010-01-01

Full Text Available Introduction Potassium iodine (KI is used as a drug therapy for treating numerous diseases such as small-vessel vasculitis, erythema nodosum, vasculitis nodularis, Sweet's syndrome, tuberculosis and granulomatosis, and for iodized salt. At the same time, KI can be harmful. Iodine intake may increase the frequency of thyroiditis in humans, and may induce the occurrence of experimental thyroiditis (ET in animals. Investigations on an experimental model for the examination of thyroiditis in Wistar rats have clearly showed morphological changes in the rat thyroid evoked by KI administration. Objective The purpose of this study was to compare the effects of low and high doses of KI on the thyroid gland of Wistar rats and determine the effect on hormone status (T4, T3 and TSH in this rat strain. Methods Two groups of rats from the Wistar strain were treated with a low iodine dose (225 μg/g BW and with a high iodine dose (675 μg/g BW of KI solutions. Untreated nonimmunized animals served as controls. The solution was administrated daily intraperitoneally during the period of 26 consecutive days. Results Monitoring hormone status (TSH, T3 and T4 and morphological changes it was found that therapeutic doses of KI applied in treatment induced the occurrence of experimental thyroiditis (chronic destructive Hashimoto's thyroiditis in humans and cell necrosis in animals not carrying a genetic susceptibility. Significant inflammatory changes were observed in rats treated with a high iodine dose. Conclusion The early iodine induced cell necrosis and inflammation in the nonimmunized animals without genetic susceptibility is a new experimental model of thyroiditis. .

Radon Concentration And Dose Assessment In Well Water Samples From Karbala Governorate Of Iraq

Science.gov (United States)

Al-Alawy, I. T.; Hasan, A. A.

2018-05-01

There are numerous studies around the world about radon concentrations and their risks to the health of human beings. One of the most important social characteristics is the use of water wells for irrigation, which is a major source of water pollution with radon gas. In the present study, six well water samples have been collected from different locations in Karbala governorate to investigate radon concentration level using CR-39 technique. The maximum value 4.112±2.0Bq/L was in Al-Hurr (Al-Qarih Al-Easariah) region, and the lowest concentration of radon was in Hay Ramadan region which is 2.156±1.4Bq/L, with an average value 2.84±1.65Bq/L. The highest result of annual effective dose (AED) was in Al-Hurr (Al-Qarih Al-Easariah) region which is equal to 15.00±3.9μSv/y, while the minimum was recorded in Hay Ramadan 7.86±2.8μSv/y, with an average value 10.35±3.1μSv/y. The current results have shown that the radon concentrations in well water samples are lower than the recommended limit 11.1Bq/L and the annual effective dose in these samples are lower than the permissible international limit 1mSv/y.

Pharmacokinetics of detomidine and its metabolites following intravenous and intramuscular administration in horses.

Science.gov (United States)

Grimsrud, K N; Mama, K R; Thomasy, S M; Stanley, S D

2009-04-01

Detomidine is commonly used i.v. for sedation and analgesia in horses, but the pharmacokinetics and metabolism of this drug have not been well described. To describe the pharmacokinetics of detomidine and its metabolites, 3-hydroxy-detomidine (OH-detomidine) and detomidine 3-carboxylic acid (COOH-detomidine), after i.v. and i.m. administration of a single dose to horses. Eight horses were used in a balanced crossover design study. In Phase 1, 4 horses received a single dose of i.v. detomidine, administered 30 microg/kg bwt and 4 a single dose i.m. 30 microg/kg bwt. In Phase 2, treatments were reversed. Plasma detomidine, OH-detomidine and COOH-detomidine were measured at predetermined time points using liquid chromatography-mass spectrometry. Following i.v. administration, detomidine was distributed rapidly and eliminated with a half-life (t1/2(el)) of approximately 30 min. Following i.m. administration, detomidine was distributed and eliminated with t1/2(el) of approximately one hour. Following, i.v. administration, detomidine clearance had a mean, median and range of 12.41, 11.66 and 10.10-18.37 ml/min/kg bwt, respectively. Detomidine had a volume of distribution with the mean, median and range for i.v. administration of 470, 478 and 215-687 ml/kg bwt, respectively. OH-detomidine was detected sooner than COOH-detomidine; however, COOH-detomidine had a much greater area under the curve. These pharmacokinetic parameters provide information necessary for determination of peak plasma concentrations and clearance of detomidine in mature horses. The results suggest that, when a longer duration of plasma concentration is warranted, the i.m. route should be considered.

Pharmacokinetics of repeated sodium salicylate administration to laying hens: evidence for time dependent increase in drug elimination from plasma and eggs.

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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.

Twice-monthly administration of a lower dose of epoetin beta pegol can maintain adequate hemoglobin levels in hemodialysis patients.

Science.gov (United States)

Morikami, Yuki; Fujimori, Akira; Okada, Shioko; Kumei, Mai; Mizobuchi, Noriko; Sakai, Makoto

2015-04-01

Epoetin beta pegol is a continuous erythropoietin receptor activator (CERA) with a long half-life. Although CERA has been shown to maintain adequate hemoglobin (Hb) levels at prolonged dosing intervals, the optimal dosing schedule remains unclear. We therefore compared the efficacy of maintaining hemoglobin levels with administration of twice-monthly CERA (TWICE) versus once-monthly CERA (ONCE). Twenty hemodialysis patients receiving epoetin beta (EPO) were enrolled in this crossover study. Patients were assigned to either the TWICE or the ONCE group based on matching Hb levels and EPO doses. After 6 months of treatment, the CERA dosage was interchanged between the groups and the study was continued for an additional 6 months. The effect of the different regimens on iron metabolism was also assessed during the first 6 months of the study. Hb levels significantly increased in the TWICE group, allowing for a reduction in CERA dosage, while the dose of CERA required to maintain Hb levels in the ONCE group remained unchanged. After the interchange, a decrease in Hb levels with incremental increase in CERA dosage was observed in the TWICE→ONCE group, with the opposite effect observed in the ONCE→TWICE group. Although increases in ferritin and hepcidin-25 levels in the ONCE group were noted at one month, they disappeared at 6 months. Although Hb levels were maintained in both the ONCE and TWICE groups, a twice-monthly administration was advantageous, as it required a lower dose of CERA. © 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.

Toxicity of TiO2 nanoparticles on soil nitrification at environmentally relevant concentrations: Lack of classical dose-response relationships.

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Simonin, Marie; Martins, Jean M F; Le Roux, Xavier; Uzu, Gaëlle; Calas, Aude; Richaume, Agnès

2017-03-01

Titanium-dioxide nanoparticles (TiO 2 -NPs) are increasingly released in agricultural soils through, e.g. biosolids, irrigation or nanoagrochemicals. Soils are submitted to a wide range of concentrations of TiO 2 -NPs depending on the type of exposure. However, most studies have assessed the effects of unrealistically high concentrations, and the dose-response relationships are not well characterized for soil microbial communities. Here, using soil microcosms, we assessed the impact of TiO 2 -NPs at concentrations ranging from 0.05 to 500 mg kg -1  dry-soil, on the activity and abundance of ammonia-oxidizing archaea (AOA) and bacteria (AOB), and nitrite-oxidizing bacteria (Nitrobacter and Nitrospira). In addition, aggregation and oxidative potential of TiO 2 -NPs were measured in the spiking suspensions, as they can be important drivers of TiO 2 -NPs toxicity. After 90 days of exposure, non-classical dose-response relationships were observed for nitrifier abundance or activity, making threshold concentrations impossible to compute. Indeed, AOA abundance was reduced by 40% by TiO 2 -NPs whatever the concentration, while Nitrospira was never affected. Moreover, AOB and Nitrobacter abundances were decreased mainly at intermediate concentrations nitrification was reduced by 25% at the lowest (0.05 mg kg -1 ) and the highest (100 and 500 mg kg -1 ) TiO 2 -NPs concentrations. Path analyses indicated that TiO 2 -NPs affected nitrification through an effect on the specific activity of nitrifiers, in addition to indirect effects on nitrifier abundances. Altogether these results point out the need to include very low concentrations of NPs in soil toxicological studies, and the lack of relevance of classical dose-response tests and ecotoxicological dose metrics (EC50, IC50…) for TiO 2 -NPs impact on soil microorganisms.

Comparative pharmacokinetics and bioavailability of albendazole sulfoxide in sheep and goats, and dose-dependent plasma disposition in goats.

Science.gov (United States)

Aksit, Dilek; Yalinkilinc, Hande Sultan; Sekkin, Selim; Boyacioğlu, Murat; Cirak, Veli Yilgor; Ayaz, Erol; Gokbulut, Cengiz

2015-05-27

The aims of this study were to compare the pharmacokinetics of albendazole sulfoxide (ABZ-SO, ricobendazole) in goats and sheep at a dose of 5 g/kg bodyweight (BW), after intravenous (IV) and subcutaneous (SC) administrations, and to investigate the effects of increased doses (10 and 15 mg/kg BW) on the plasma disposition of ABZ-SO in goats following SC administration. A total of 16 goats (Capra aegagrus hircus, eight males and eight females) and 8 sheep (Ovis aries, four males and four females) 12-16 months old and weighing 20-32 kg, were used. The study was designed according to two-phase crossover study protocol. In Phase-1, eight sheep were assigned as Group I and 16 goats were allocated into two groups (Group II and Group III). ABZ-SO was applied to Group I (sheep) and Group II (goats) animals subcutaneously, and to Group III (goats) animals intravenously, all at a dose rate of 5 mg/kg BW. In Phase-2, the sheep in the Group I received ABZ-SO intravenously in a dose of 5 mg/kg BW; the goats in Group II and Group III received ABZ-SO subcutaneously at a dose of 10 mg/kg and 15 mg/kg BW, respectively. Blood samples were collected from the jugular vein at different times between 1 and 120 h after drug administrations. The plasma concentrations of ABZ-SO and its metabolites were analysed by high performance liquid chromatography. In goats, the area under the curve, terminal half-life and plasma persistence of ABZ-SO were significantly smaller and shorter, respectively, compared with those observed in sheep following both IV and SC administrations at a dose of 5 mg/kg BW. On the other side, dose-dependent plasma dispositions of ABZ-SO were observed following SC administration at increased doses (10 and 15 mg/kg) in goats. Consequently, ABZ-SO might be used at higher doses to provide higher plasma concentration and thus to achieve greater efficacy against the target parasites.

Effect of Photon Beam Energy, Gold Nanoparticle Size and Concentration on the Dose Enhancement in Radiation Therapy

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Nahideh Gharehaghaji

2013-02-01

Full Text Available Introduction: Gold nanoparticles have been used as radiation dose enhancing materials in recent investigations. In the current study, dose enhancement effect of gold nanoparticles on tumor cells was evaluated using Monte Carlo (MC simulation. Methods: We used MCNPX code for MC modeling in the current study. A water phantom and a tumor region with a size of 1×1×1 cm3 loaded with gold nanoparticles were simulated. The macroscopic dose enhancement factor was calculated for gold nanoparticles with sizes of 30, 50, and 100 nm. Also, we simulated different photon beams including mono-energetic beams (50-120 keV, a Cobalt-60 beam, 6 & 18 MV photon beams of a conventional linear accelerator. Results: We found a dose enhancement factor (DEF of from 1.4 to 3.7 for monoenergetic kilovoltage beams, while the DEFs for megavoltage beams were negligible and less than 3% for all GNP sizes and concentrations. The optimum energy for higher DEF was found to be the 90 keV monoenergetic beam. The effect of GNP size was not considerable, but the GNP concentration had a substantial impact on achieved DEF in GNP-based radiation therapy. Conclusion: The results were in close agreement with some previous studies considering the effect of photon energy and GNP concentration on observed DEF. Application of GNP-based radiation therapy using kilovoltage beams is recommended.

Effects of hypertonic buffer composition on lymph node uptake and bioavailability of rituximab, after subcutaneous administration.

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Fathallah, Anas M; Turner, Michael R; Mager, Donald E; Balu-Iyer, Sathy V

2015-03-01

The subcutaneous administration of biologics is highly desirable; however, incomplete bioavailability after s.c. administration remains a major challenge. In this work we investigated the effects of excipient dependent hyperosmolarity on lymphatic uptake and plasma exposure of rituximab as a model protein. Using Swiss Webster (SW) mice as the animal model, we compared the effects of NaCl, mannitol and O-phospho-L-serine (OPLS) on the plasma concentration of rituximab over 5 days after s.c. administration. An increase was observed in plasma concentrations in animals administered rituximab in hypertonic buffer solutions, compared with isotonic buffer. Bioavailability, as estimated by our pharmacokinetic model, increased from 29% in isotonic buffer to 54% in hypertonic buffer containing NaCl, to almost complete bioavailability in hypertonic buffers containing high dose OPLS or mannitol. This improvement in plasma exposure is due to the improved lymphatic trafficking as evident from the increase in the fraction of dose trafficked through the lymph nodes in the presence of hypertonic buffers. The fraction of the dose trafficked through the lymphatics, as estimated by the model, increased from 0.05% in isotonic buffer to 13% in hypertonic buffer containing NaCl to about 30% for hypertonic buffers containing high dose OPLS and mannitol. The data suggest that hypertonic solutions may be a viable option for improving s.c. bioavailability. Copyright © 2014 John Wiley & Sons, Ltd.

Pharmacokinetics of (/sup 3/H)levamisole in pigs after oral and intramuscular administration

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Galtier, P.; Escoula, L.; Alvinerie, M.

1983-04-01

A single oral (10 mg/kg of body weight) or IM (7.5 mg/kg) dose of (/sup 3/H)levamisole was administered to pigs. Liquid scintillation counting and high performance liquid chromatography were used to determine total radioactivity and drug levels in plasma, duodenal and cecal contents, bile, and urine for 24 and 72 hours after dosing. Pharmacokinetic analysis indicated a 1-compartment open model with higher plasma bioavailability of levamisole after IM injection. Biological half-lives for elimination of the drug were 9.3 and 6.9 hours after oral and IM administration, respectively. Anthelmintic concentrations were higher in intestinal contents after oral gavage than after IM injection. The drug appeared extensively metabolized in all body fluids and particularly in bile, regardless of the route of administration. Biliary excretion of radioactivity and unchanged levamisole represented only slight percentages of the administered dose (approx 0.4% and 4.2%, respectively, in 72 hours). In contrast, about 60% and 20% of the dose were eliminated via urine as tritiated materials and unchanged drug. The choice of the most efficacious route of administration is discussed in regard to localization of helminthic disease.

Activity concentrations and mean annual effective dose of foodstuffs on the island of Tenerife (Spain))

International Nuclear Information System (INIS)

Hernandez, F.; Hernandez-Armas, J.; Catalan, A.; Fernandez-Aldecoa, J. C.; Landeras, M. I.

2004-01-01

A total of 26 different food types and 12 elaborated diets were analysed by low-level gamma spectrometry to measure their content of 238 U( 234 Th), 228 Ra( 228 Ac), 226 Ra( 214 Pb), 210 Pb, 137 Cs and 40 K. The concentrations of these radionuclides measured in some imported foodstuffs were compared with those measured in some locally produced ones. Moreover, the concentrations found in the analysed foodstuffs and composite diets were compared with the data available in literature from other locations, such as Egypt (Brazil)) (Poland)) and Hong Kong. 40 K contributed highest to the daily dose produced by the intake of comestibles. The largest 40 K concentrations were measured in the chickpeas and beans with 380 ± 30 and 380 ± 20 Bq kg -1 fresh weights, respectively. The artificial radionuclide 137 Cs was measured only above detection limits in the potatoes and sweet potatoes. A mean annual effective dose of 362 μSv with a standard deviation of 110 μSv was calculated from the composite diets. (authors)

Clinical evaluation of the hypoxic cytotoxin tirapazamine (SR-4233): phase I experience with repeated dose administration during fractionated irradiation

International Nuclear Information System (INIS)

Hancock, Steven L.; Spencer, Sharon; Mariscal, Carol; Wooten, Ann; Wheeler, Richard; Brown, J. Martin; Fisher, Cheryl; Roemeling, Reinhard von

1996-01-01

Purpose: Regions of chronic or transient hypoxia are common in many human tumors and are thought to limit tumor cell killing and tumor control with conventional irradiation and some chemotherapeutic agents. Tirapazamine (3-amino-1,2,4-benzotriazine-1,4-di-N-oxide) forms a cytotoxic free radical during reductive metabolism in regions of hypoxia. In well oxygenated regions, the tirapazamine radical reacts with molecular oxygen to form the inactive parent drug. This results in markedly greater toxicity for hypoxic cells than for the well oxygenated cells that comprise most normal tissues. Tirapazamine increased the anti-tumor effects of single dose or fractionated irradiation or cis-platin chemotherapy in murine tumors,in vivo . This study evaluated the ability to repeat the administration of Tirapazamine during courses of fractionated irradiation in humans after an earlier phase I trial established a maximum tolerated dose of 390 mg per square meter of body surface area (mg/m 2 ) when given as a single dose with radiotherapy. Materials and Methods: Between December 1993 and August 1995 22 patients with locally advanced or metastatic tumors of varying histology, normal renal, hepatic, and hematologic functions, and Karnofsky performance status ≥ 60 received repeated doses of Tirapazamine during a planned, 6 weeks course of standardly fractionated radiotherapy. After anti-emetic treatment with ondansetron (32 mg) and dexamethasone (16 mg), Tirapazamine was administered during a 2 hour intravenous infusion that ended from 30 to 90 minutes before a radiation treatment. Patients were monitored for acute toxicity during the course of treatment and for a minimum of one month after radiotherapy. Results: The study was initiated with three, biweekly doses of Tirapazamine at 330 mg/m 2 . Four of 7 patients who initiated treatment at this dose refused the second (1 patient) or third dose of Tirapazamine (3 patients). Two of the three patients who received three doses

Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes.

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Liu, Chi; Kurokawa, Ryosuke; Fujino, Masayuki; Hirano, Shinichi; Sato, Bunpei; Li, Xiao-Kang

2014-06-30

Hydrogen exerts beneficial effects in disease animal models of ischemia-reperfusion injury as well as inflammatory and neurological disease. Additionally, molecular hydrogen is useful for various novel medical and therapeutic applications in the clinical setting. In the present study, the hydrogen concentration in rat blood and tissue was estimated. Wistar rats were orally administered hydrogen super-rich water (HSRW), intraperitoneal and intravenous administration of hydrogen super-rich saline (HSRS), and inhalation of hydrogen gas. A new method for determining the hydrogen concentration was then applied using high-quality sensor gas chromatography, after which the specimen was prepared via tissue homogenization in airtight tubes. This method allowed for the sensitive and stable determination of the hydrogen concentration. The hydrogen concentration reached a peak at 5 minutes after oral and intraperitoneal administration, compared to 1 minute after intravenous administration. Following inhalation of hydrogen gas, the hydrogen concentration was found to be significantly increased at 30 minutes and maintained the same level thereafter. These results demonstrate that accurately determining the hydrogen concentration in rat blood and organ tissue is very useful and important for the application of various novel medical and therapeutic therapies using molecular hydrogen.

Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes

Science.gov (United States)

Liu, Chi; Kurokawa, Ryosuke; Fujino, Masayuki; Hirano, Shinichi; Sato, Bunpei; Li, Xiao-Kang

2014-01-01

Hydrogen exerts beneficial effects in disease animal models of ischemia-reperfusion injury as well as inflammatory and neurological disease. Additionally, molecular hydrogen is useful for various novel medical and therapeutic applications in the clinical setting. In the present study, the hydrogen concentration in rat blood and tissue was estimated. Wistar rats were orally administered hydrogen super-rich water (HSRW), intraperitoneal and intravenous administration of hydrogen super-rich saline (HSRS), and inhalation of hydrogen gas. A new method for determining the hydrogen concentration was then applied using high-quality sensor gas chromatography, after which the specimen was prepared via tissue homogenization in airtight tubes. This method allowed for the sensitive and stable determination of the hydrogen concentration. The hydrogen concentration reached a peak at 5 minutes after oral and intraperitoneal administration, compared to 1 minute after intravenous administration. Following inhalation of hydrogen gas, the hydrogen concentration was found to be significantly increased at 30 minutes and maintained the same level thereafter. These results demonstrate that accurately determining the hydrogen concentration in rat blood and organ tissue is very useful and important for the application of various novel medical and therapeutic therapies using molecular hydrogen. PMID:24975958

Would Be Prophylactic Administrations of Low Concentration of Alendronate an Alternative for Improving the Craniofacial Bone Repair? A Preliminary Study Focused in the Period of Cellular Differentiation and Tissue Organization.

Science.gov (United States)

Göhringer, Isabella; Muller, Carmem L Storrer; Cunha, Emanuelle Juliana; Passoni, Giuliene Nunes De Souza; Vieira, Juliana Souza; Zielak, João Cesar; Scariot, Rafaela; Deliberador, Tatiana Miranda; Giovanini, Allan Fernando

2017-10-01

Alendronate (ALN) is a nitrogen-bisphosphonate that may induce an anabolic effect on craniofacial bone repair when administrated in low doses. Based on this premise, this study analyzed the influence of prophylactic low doses of ALN on bone healing in defects created in rabbit mandible. A 5 × 2-mm diameter deep defect was created in the calvaria of 28 rabbits. Fourteen of these rabbits received previously 50 μg/kg of 1% sodium ALN for 4 weeks, while the other rabbits received only 0.9% physiological saline solution (control). Animals were euthanized at 15 and 60 days postsurgery (n = 7), and the data were analyzed using histomorphometry and immunohistochemistry using the anti-CD34, bone morphogenetic protein -2 (BMP-2), and transforming growth factor (TGF)-β1 antibodies. On the 15th day postsurgery, the specimens that received previous treatment with ALN demonstrated large vascular lumen and intense positivity to CD34 either concentrated in endothelium or cells spread among the reparative tissue. These results coincided with intense positivity for BMP-2+ cells and TGF-β1 that was concentrated in both cells and perivascular area. In contrast, the control group revealed scarce cells that exhibited CD34, BMP-2+, and the TGF-β1 was restricted for perivascular area on well-formed granulation tissue. These patterns of immunohistochemical result, especially found on the 15th day of analysis, seem to be responsible for the development of larger quantities of bone matrix in the specimens that receive ALN on the 60th day postsurgery. These preliminary results showed that the prophylactic administration of low doses of ALN might be an alternative to craniofacial bone craniofacial bone repair because it increases the immunopositivity for TGF-β1 and consequently improves the CD34+ and BMP-2+ cells on reparative sites.

Successful pregnancy following low-dose hCG administration in addition to hMG in a patient with hypothalamic amenorrhea due to weight loss.

Science.gov (United States)

Tsutsumi, Ryo; Fujimoto, Akihisa; Osuga, Yutaka; Harada, Miyuki; Takemura, Yuri; Koizumi, Minako; Yano, Tetsu; Taketani, Yuji

2012-06-01

We describe successful ovulation induction with low-dose hCG administration in addition to hMG in a patient with refractory hypothalamic amenorrhea. A 24-year-old woman with weight loss-related amenorrhea underwent ovulation induction and intracytoplasmic sperm injection (ICSI). Administration of exogenous gonadotropins was ineffective in ovulation induction. Supplementation with low-dose hCG in order to increase luteinizing hormone (LH) activity in the late follicular phase produced late folliculogenesis and steroidogenesis, and ovulation was then successfully induced. This report reacknowledges the critical role that LH plays cooperatively with follicle-stimulating hormone in both folliculogenesis and steroidogenesis.

Single-Dose Pharmacokinetics of Piperacillin/Tazobactam in Hispaniolan Amazon Parrots ( Amazona ventralis ).

Science.gov (United States)

Carpenter, James W; Tully, Thomas N; Gehring, Ronette; Guzman, David Sanchez-Migallon

2017-06-01

To determine the pharmacokinetics of piperacillin/tazobactam in Hispaniolan Amazon parrots ( Amazona ventralis ), 8 healthy adult parrots of both sexes were used in a 2-part study. In a pilot study, piperacillin (87 mg/kg) in combination with tazobactam (11 mg/kg) was administered intramuscularly (IM) to 2 birds, and blood samples were obtained at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours after administration. Based on the results obtained, a main study was done in which piperacillin/tazobactam was administered at 2 different doses. In 3 birds, the initial dose of piperacillin (87 mg/kg)/tazobactam (11 mg/kg) IM was administered, and in 3 birds, the dose was doubled to piperacillin (174 mg/kg)/tazobactam (22 mg/kg) IM. In all 6 birds, blood samples were obtained at 0, 5, 15, and 30 minutes and at 1, 1.5, 2, 2.5, 3, and 4 hours after administration. Quantification of plasma piperacillin and tazobactam concentrations was determined by validated liquid chromatography-mass spectrometry assay. Pharmacokinetic parameters were determined by noncompartmental analysis. After intramuscular administration, the mean ± standard error values of T 1/2 (h) was 0.52 ± 0.05 and 0.32 ± 0.07, T max (h) was 0.28 ± 0.09 and 0.25 ± 0.10, C max (μg/mL) was 86.34 ± 20.62 and 9.03 ± 2.88, and C max /dose was 0.99 ± 0.24 and 0.83 ± 0.26 for piperacillin (87 mg/kg) and tazobactam (11 mg/kg), respectively. When the doses were doubled, the T 1/2 (h) was 0.65 ± 0.08 and 0.34 ± 0.02, T max (h) was 0.28 ± 0.12 and 0.14 ± 0.06, C max (μg/mL) was 233.0 ± 6.08 and 22.13 ± 2.35, and C max /dose was 1.34 ± 0.03 and 1.02 ± 0.11 for piperacillin and tazobactam, respectively. Results indicate that piperacillin is rapidly absorbed and reaches high initial concentrations; however, it is also rapidly eliminated in the Hispaniolan Amazon parrot, and tazobactam has similar pharmacokinetics as piperacillin. Administration of piperacillin at 87 mg/kg IM q3-4h is recommended for this species

Effect of donepezil hydrochloride (E2020) on extracellular acetylcholine concentration in the cerebral cortex of rats.

Science.gov (United States)

Kosasa, T; Kuriya, Y; Yamanishi, Y

1999-10-01

Donepezil hydrochloride (donepezil), a potent and selective acetylcholinesterase inhibitor, has been developed for the treatment of Alzheimer's disease. We studied the effect of oral administration of this drug on the extracellular acetylcholine (ACh) concentration in the cerebral cortex of rats using microdialysis. We also observed fasciculation, a peripheral cholinergic sign induced by activation of neuromuscular transmission, after oral administration of the drug as an index of peripheral cholinergic activation. Other cholinesterase inhibitors, tacrine, ENA-713 and TAK-147, were used as reference drugs. Donepezil significantly and dose-dependently increased the extracellular ACh concentration in the rat cerebral cortex within the dose range of 2.5-10 mg/kg. Tacrine, ENA-713 and TAK-147 also elevated the extracellular concentration of ACh. The minimum effective doses of donepezil, tacrine, ENA-713 and TAK-147 were (< or = 2.5, 10, 10 and < or = 10 mg/kg, respectively. Donepezil produced fasciculation at doses of 2.5 mg/kg and above, with a dose-dependent increase in incidence and intensity. The reference compounds also induced fasciculation in a dose-dependent manner. The threshold doses of tacrine, ENA-713 and TAK-147 for fasciculation were 5, 2.5 and 2.5 mg/kg, respectively. The values of the ratio of the minimum effective dose for the ACh-increasing action to that for the fasciculation-producing action were: donepezil, < or = 1; tacrine, 2; ENA-713, 4; TAK-147, < or = 4. These results indicate that orally administered donepezil has a potent and selective activity on the central cholinergic system.

Twelve-hour brain lithium concentration in lithium maintenance treatment of manic-depressive disorder: daily versus alternate-day dosing schedule

DEFF Research Database (Denmark)

Jensen, H.V.; Plenge, P; Stensgaard, A

1996-01-01

The 12-h brain lithium concentration was measured by lithium-7 magnetic resonance spectroscopy in ten manic-depressive patients receiving daily or alternate-day lithium carbonate treatment. The median dose of lithium carbonate was 800 mg in the daily treatment group and 1200 mg in the alternate......-day group. Median 12-h serum lithium concentration in the two groups was 0.86 mmol l-1 and 0.55 mmol l-1, respectively, while the corresponding concentration in brain was 0.67 mmol l-1 and 0.52 mmol l-1, respectively. The 12-h brain lithium concentration was independent of lithium dosing schedule (multiple...... linear regression), but correlated significantly with the 12-h serum lithium concentration (P = 0.003; B = 0.53, 95% c.l. 0.24-0.82; beta = 0.83). Thus at identical 12-h serum lithium concentrations the 12-h brain lithium concentration is similar with both treatment regimes. As the risk of manic...

Effects of Different Administration Protocols on the Plasma Concentration of Donepezil Hydrochloride in Dementia Patients with Stage 5 Chronic Kidney Disease

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Chika Amano

2013-06-01

Full Text Available The prevalence of chronic kidney disease (CKD as well as Alzheimer's disease (AD increases with age. With the aging of the population in Japan, there is an increasing likelihood that patients with CKD will receive donepezil hydrochloride (DPZ, an antidementia drug, in the near future. Nevertheless, there have been few reports on how to use DPZ in patients with severe CKD. We report on 2 CKD stage 5 patients who received DPZ under different prescriptions. In case 1, 3 mg/day of DPZ was initially administered for 4 months, after which the dose was increased to 5 mg/day. In case 2, 5 mg was administered twice a week. The plasma concentration of DPZ was measured and the effectiveness was assessed using the Mini-Mental Health State Examination and the Hasegawa Dementia Rating Scale. We found that (1 only a slight increase in the plasma concentration of DPZ was observed with a dose of 3 mg daily, (2 there was a significant increase in the plasma concentration with a dose of 5 mg daily, and (3 when 5 mg of DPZ was administered twice a week, the plasma concentration did not differ significantly from healthy controls who had received 5 mg daily. Although cognitive function was improved best when the 5-mg dose was administered daily with no apparent side effects, the plasma concentration came close to reaching a toxic level at this dose. Careful follow-up may be essential when DPZ is used at 5 mg/day or greater in severe CKD patients.

Different concentrations and volumes of p-phenylenediamine in pet. (equivalent doses) are associated with similar patch test outcomes

DEFF Research Database (Denmark)

Andersen, Flemming; Hamann, Carsten R; Andersen, Klaus E

2018-01-01

BACKGROUND: Concern about causing active sensitization when patch testing is performed with p-phenylenediamine (PPD) 1% pet. has led to a recommendation to use PPD 0.3% pet. as a potentially safer preparation. However, the dose per area of allergen delivered, and hence the risk of active...... sensitization, depend on the amount dispensed into the patch test chamber, which can vary widely. OBJECTIVE: To evaluate whether patch testing with equivalent doses of different concentrations of PPD in pet. is associated with similar outcomes. METHODS: Seventeen known PPD-sensitive subjects were patch tested...... with different volumes and concentrations of PPD in pet. that deliver the same allergen dose per unit area (6 mg of PPD 1% pet. and 20 mg of PPD 0.3% pet. in Finn Chambers®, both equivalent to ∼ 0.09 mg/cm2 ). RESULTS: Eleven patients (65%) had positive reactions to both doses; 4 patients (24%) had negative...

Irradiation of mammalian cells in the presence of diamide and low concentrations of oxygen at conventional and at ultrahigh dose rates

International Nuclear Information System (INIS)

Clark, E.P.; Michaels, H.B.; Peterson, E.C.; Epp, E.R.

1983-01-01

The response of cultured CHO cells to ultrahigh-dose-radiation (approx.10 9 Gy/sec) has been previously studied extensively using the thin-layer cell-handling technique developed in this laboratory. When the cells are equilibrated with a low concentration of oxygen, e.g., 0.44% O 2 , a breaking survival curve, due to radiolytic depletion of the oxygen, is observed. Hypoxic cells irradiated in the presence of the nitroimidazoles (e.g., misonidazole) are sensitized at ultrahigh dose rates in a dose-modifying manner, similar to that observed at conventional dose rates. These radiosensitizer compounds, if present in cells equilibrated with a low concentration of oxygen, prevent the breaking behavior of the survival curve, an observation believed to be due to the sensitizer interfering with the oxygen depletion process, leaving oxygen free to sensitize. Such experiments have recently been extended to studies with diamide, which, unlike the other sensitizers tested, acts primarily as a shoulder-modifying rather than a dose-modifying agent in hypoxic mammalian cells. These data indicate that diamide is active as a sensitizer at ultrahigh dose rates in a manner similar to that observed at conventional dose rates, and does modify the shape of the breaking survival curve observed with low concentrations of oxygen

Natural Radionuclides and 137Cs Concentrations in Rice in Jepara Residence and Internal Dose Estimation Intake by the People

International Nuclear Information System (INIS)

Leli-Nirwani; Minarni; Buchari

2001-01-01

The measurement of natural radionuclides and 137 Cs concentration in rice in Jepara residence and internal dose estimation intake by people have been conducted. The aim of the research is to determine internal dose estimation of natural radionuclides and 137 Cs intake by people in Jepara residence. By knowing the natural radionuclides and 137 Cs concentrations in rice at Jepara residence, the dose coefficient for adult from ICRP No.72 and the annual intake consumption take from the Indonesian food balance published by BPS, the internal dose from natural radionuclides and 137 Cs intake from food can be calculate concentration of 228 Th, 226 Ra and 137 Cs were found in Bayuran, with the average value was (2.00±0.21) x 10 -5 Bq/kg, (0.09±0.25) x 10 -5 Bq/kg, (19.00±0.06) x 10 -5 Bq/kg respectively the highest 40 K concentration was found in Pandansili with the average was about (8.40 ± 0.34) x 10 -5 Bq/kg. The estimation of equivalent doses from intake of 228 Th, 226 Ra, 40 K, and 137 Cs in rice were the highest in Bayuran the value the average values, respectively, was 0.0039 x 10 -5 μ Sv/yr, 18.09 X 10 -5 μ Sv/yr, 1.63 x 10 -5 μ Sv/yr, 172.38 x 10 -5 μ Sv/yr. Result in this measurement lowest comparing by recommendation IAEA in Safety Series No. 115 in 1996. (author)

Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration

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Berkó S

2016-05-01

Full Text Available Szilvia Berkó,1,* Kálmán F Szűcs,2,* Boglárka Balázs,1,3 Erzsébet Csányi,1 Gábor Varju,4 Anita Sztojkov-Ivanov,2 Mária Budai-Szűcs,1 Judit Bóta,2 Róbert Gáspár2 1Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Szeged, Szeged, Hungary; 2Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary; 3Gedeon Richter Plc., Budapest, 4Dr Derm Clinic of Anti-Aging Dermatology, Aesthetic Laser and Plastic Surgery, Budapest, Hungary *These authors contributed equally to this work Purpose: Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats. Methods: The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. Results: Both intravenously and EP-administered neostigmine (0.2–66.7 µg/kg increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 µg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes. Conclusion: The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice. Keywords: transdermal

Variation of indoor radon progeny concentration and its role in dose assessment

International Nuclear Information System (INIS)

Singh, Manmohan; Singh, Kulwant; Singh, Surinder; Papp, Z.

2008-01-01

Instantaneous measurements of equilibrium equivalent concentration of radon (EEC Rn ) were taken over a period of 1 year in 2004 in a typical house at Amritsar city, located in the northwest part of India. A method based on absolute beta counting subsequent to grab aerosol sampling was used. During that year, EEC Rn varied between 1.56 Bq m -3 and 22.77 Bq m -3 with average value of 8.76 Bq m -3 . EEC Rn decreased with the transition from winter to summer and vice versa, having a negative correlation with outdoor temperature. The use of mechanical ventilation, under normal living conditions during summer, caused an extra decrease in the concentrations. The variations with temperature and mechanical ventilation are discussed. Some major issues related to the uncertainties in dose calculations caused by the lack of knowledge of equilibrium factor and ignoring the effect of life style on the radon and its progeny concentrations are discussed

Dose and duration dependent of aluminium in the serum liver and ...

African Journals Online (AJOL)

An atomic absorption spectrophotometric analysis on dose and duration dependent aluminum concentration in serum, liver and brain digests of three groups of male Wistar albino rats were investigated after seven and fourteen days of daily 0.38mg/kg, 3.8mg/kg and 38mg/kg aluminum administration respectively.

Single-dose, subcutaneous recombinant phenylalanine ammonia lyase conjugated with polyethylene glycol in adult patients with phenylketonuria: an open-label, multicentre, phase 1 dose-escalation trial.

Science.gov (United States)

Longo, Nicola; Harding, Cary O; Burton, Barbara K; Grange, Dorothy K; Vockley, Jerry; Wasserstein, Melissa; Rice, Gregory M; Dorenbaum, Alejandro; Neuenburg, Jutta K; Musson, Donald G; Gu, Zhonghua; Sile, Saba

2014-07-05

. By the end of the study, all participants had developed antibodies against polyethylene glycol, and some against phenylalanine ammonia lyase as well. Drug concentrations peaked about 89-106 h after administration of the highest dose. Treatment seemed to be effective at reducing blood phenylalanine in all five participants who received the highest dose (mean reduction of 54·2% from baseline), with a nadir about 6 days after injection and an inverse correlation between drug and phenylalanine concentrations in plasma. Phenylalanine returned to near-baseline concentrations about 21 days after the injection. Subcutaneous administration of rAvPAL-PEG in a single dose of up to 0·100 mg/kg was fairly safe and well tolerated in adult patients with phenylketonuria. At the highest dose tested, rAvPAL-PEG reduced blood phenylalanine concentrations. In view of the development of antibodies against polyethylene glycol (and in some cases against phenylalanine ammonia lyase), future studies are needed to assess the effect of repeat dosing. BioMarin Pharmaceutical. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of Enrofloxacin Administration on Semen Quality of Barbari bucks

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Chandrima Sinha

2012-07-01

Full Text Available The present study was undertaken to study the effect of enrofloxacin administration on semen quality of Barbari buck. Six normal, healthy adult Barbari bucks (25-30 Kg aged between 2 to 2.5 years were used as semen donors. The bucks were administered enrofloxacin at the dose of 5mg/kg body weight intra-muscularly daily for 7 days. From each buck biweekly eighteen semen ejaculates (1st to 18th were collected and one sample (0th from each buck was collected before administration of enrofloxacin, using a non-oestrous doe as dummy and investigated for semen quality parameters. There was no significant difference (P≥0.05 in seminal volume between different ejaculates. Mass motility decreased significantly (P≤0.01 and was lowest in 4th ejaculate as compared to mass motility prior to drug administration. Highest significant (P≤0.01 decrease in progressive motility was seen in 9th ejaculate as compared to progressive motility before drug administration. Sperm concentration decreased significantly (P≤0.01 and was found to be lowest in 4th ejaculate as compared to sperm concentration before enrofloxacin administration. Percent live spermatozoa decreased significantly (P≤0.01 and was found to be minmum in 12th ejaculate as compared to sperm concentration prior to drug administration. Highest significant increase (P≤ 0.01 in per cent head, mid-piece and tail abnormalities of spermatozoa was observed in 4th, 3rd and 6th ejaculate respectively following parentral administration of enrofloxacion as compared to ejaculate before drug administration. Following drug administration, the semen quality decreased progressively and then became slowly normal after 14th ejaculate.

Disposition of 2,4-dichlorophenoxyacetic acid dimethylamine by Fischer 344 rats dosed orally and dermally

International Nuclear Information System (INIS)

Pelletier, O.; Ritter, L.; Caron, J.; Somers, D.

1989-01-01

The dimethylamine salt of 14C-ring-labeled 2,4-D was administered to Fischer 344 rats orally (1 and 0.4 mg/kg body weight) and dermally (10 mg/kg body weight). Absorption, distribution, and elimination were determined from 14C-labeled 2,4-D in blood, tissues, and excreta. Quantitatively, most of the orally administered dose (94-96%) became systemically available within 6 h. Following dermal administration 10% of the dose became systemically available over 72 h. However, peak concentrations in blood and kidneys were achieved within 30 min of dosing by either route. By 1.5 h after dosing, 2,4-D concentrations in blood, muscle, liver, and kidneys had decreased in both the orally dosed and dermally dosed animals. Between 2 and 8 h, the blood, muscle, liver and kidney concentrations in dermally dosed animals maintained a plateau while urinary excretion increased, presumably due to continued absorption of 2,4-D from the skin. The concentrations in orally dosed animals continued to decrease. Following 7 h of dermal exposure, skin cleansing removed about 63% of the applied dose; about 17% of the applied dose remained at the site of dermal dosing. At 8 h, 2,4-D concentrations in blood, muscle, liver, and kidneys of dermally dosed animals began to decrease, most likely a result of the removal of the reservoir on the skin. However, 2,4-D continued to be absorbed from skin site, resulting in a slower decline of the 2,4-D concentrations in these tissues over remainder of the 72-h study period. By comparison, in animals that had been orally dosed, the absorbed dose was almost completely excreted within 24 h

The effect of dosing regimen on the pharmacokinetics of risedronate

Science.gov (United States)

Mitchell, David Y; Heise, Mark A; Pallone, Karen A; Clay, Marian E; Nesbitt, John D; Russell, Darrell A; Melson, Chad W

1999-01-01

Aims To examine the effect of timing of a risedronate dose relative to food intake on the rate and extent of risedronate absorption following single-dose, oral administration to healthy male and female volunteers. Methods A single-dose, randomized, parallel study design was conducted with volunteers assigned to four treatment groups (31 or 32 subjects per group, 127 subjects total). Each subject was orally administered 30 mg risedronate. Group 1 was fasted for 10 h prior to and 4 h after dosing (fasted group); Groups 2 and 3 were fasted for 10 h and were dosed 1 and 0.5 h, respectively, before a high-fat breakfast; and Group 4 was dosed 2 h after a standard dinner. Blood and urine samples were collected for 168 h after dosing. Pharmacokinetic parameters were estimated by simultaneous analysis of risedronate serum concentration and urinary excretion rate-time data. Results Extent of risedronate absorption (AUC and Ae) was comparable (P = 0.4) in subjects dosed 2 h after dinner and 0.5 h before breakfast; however, a significantly greater extent of absorption occurred when risedronate was given 1 or 4 h prior to a meal (1.4- to 2.3-fold greater). Administration 0.5, 1, or 4 h prior to a meal resulted in a significantly greater rate of absorption (Cmax 2.8-, 3.5-, and 4.1-fold greater, respectively) when compared with 2 h after dinner. Conclusions The comparable extent of risedronate absorption when administered either 0.5–1 h before breakfast or 2 h after an evening meal support previous clinical studies where risedronate was found to have similar effectiveness using these dosing regimens. This flexibility in the timing of risedronate administration may provide patients an alternative means to achieve the desired efficacy while maintaining their normal daily routine. PMID:10583024

Pharmacokinetics of oral neratinib during co-administration of ketoconazole in healthy subjects.

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Abbas, Richat; Hug, Bruce A; Leister, Cathie; Burns, Jaime; Sonnichsen, Daryl

2011-04-01

The primary objective was to evaluate the pharmacokinetics of a single dose of neratinib, a potent, low-molecular-weight, orally administered, irreversible pan-ErbB (ErbB-1, -2, -4) receptor tyrosine kinase inhibitor, during co-administration with ketoconazole, a potent CYP3A4 inhibitor. This was an open-label, randomized, two-period, crossover study. Fasting healthy adults received a single oral dose of neratinib 240 mg alone and with multiple oral doses of ketoconazole 400 mg. Blood samples were collected up to 72 h after each neratinib dose. Plasma concentration data were analyzed using a noncompartmental method. The least square geometric mean ratios [90% confidence interval (CI)] of C(max) (neratinib+ketoconazole): C(max) (neratinib alone), and AUC(neratinib+ketoconazole): AUC(neratinib alone) were assessed. Twenty-four subjects were enrolled. Compared with neratinib administered alone, co-administration of ketoconazole increased neratinib C(max) by 3.2-fold (90% CI: 2.4, 4.3) and AUC by 4.8-fold (3.6, 6.5). Median t(max) was 6.0 h with both regimens. Ketoconazole decreased mean apparent oral clearance of neratinib from 346 lh(-1) to 87.1 lh(-1) and increased mean elimination half-life from 11.7 h to 18.0 h. The incidence of adverse events was comparable between the two regimens (50% neratinib alone, 65% co-administration with ketoconazole). Co-administration of neratinib with ketoconazole, a potent CYP3A inhibitor, increased neratinib C(max) by 3.2-fold and AUC by 4.8-fold compared with administration of neratinib alone. These results indicate that neratinib is a substrate of CYP3A and is susceptible to interaction with potent CYP3A inhibitors and, thus, dose adjustments may be needed if neratinib is administered with such compounds. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Radiation dose to bladder wall following the administration of sup(99m)Tc-microspheres and sup(99m)Tc-DTPA

International Nuclear Information System (INIS)

Smith, T.

1981-01-01

Castronovo et al. (Health Phys. Vol. 39, p 112, 1980) reported a method of calculating the dose to the bladder wall following administration of sup(99m)Tc human albumin microspheres (sup(99m)Tc-HAM) for lung perfusion scanning. The present note comments that (1) the dosimetry is estimated for an unusual bladder voiding schedule and no indication is given of the variation of dose to be expected with different schedules, and (2) that the method assumes linear biological excretion of the radiopharmaceutical into the bladder in any particular filling period. It is shown that whilst this is a valid approximation in the case considered, it is not a generally applicable principle. Values of bladder wall dose commitments following intravenous administration of sup(99m)Tc-HAM or sup(99m)Tc DTPA are tabulated. Values for constant voiding cycles are presented for four different bladder voiding periods between 2 and 8 hr, and for three different methods of calculation:-a method described in this paper, the linear excretion method of Castronovo et al., and the method of Snyder et al. (ORNL-4584, pp. 206-208, 1970) which allows for urine flow rate. (U.K.)

Efficiency of early, single-dose probiotic administration methods on performance, small intestinal morphology, blood biochemistry, and immune response of Japanese quail.

Science.gov (United States)

Seifi, Kazem; Karimi Torshizi, Mohammad Amir; Rahimi, Shaban; Kazemifard, Mohammad

2017-07-01

The aim of the present study was to investigate the efficacy of early probiotics (single dose) administered in different ways, on quails' performance, small intestine morphology, blood biochemistry, and immune response. In total, 192 day-old chicks were used in one of the following experimental groups before being transferred to a raising room: 1) Control (no probiotic administered), 2) oral gavage, 3) spray, and 4) vent lip. Four replicates of 12 chicks per cage were considered for each treatment and birds were raised up to 35 d in the same conditions. Probiotic treated birds had higher d 1 to 35 feed intake than the control group (P birds had a higher body weight gain as compared to the control (P birds compared to control (P  0.01). None of the immune-related parameters were affected by the probiotic (P > 0.05). Single dose usage of probiotics exerts its beneficial effects on quails' body weight gain, feed intake and mortality in 1 to 35 d period, regardless of the route of administration. This work generally supports the efficacy of single-dose usage of probiotics and suggests the spray of probiotics as an early, single-dose administration method. © 2017 Poultry Science Association Inc.

Isoflurane minimum alveolar concentration sparing effects of fentanyl in the dog.

Science.gov (United States)

Williamson, Allan J; Soares, Joao H N; Pavlisko, Noah D; McAlister Council-Troche, Robert; Henao-Guerrero, Natalia

2017-07-01

To characterize the isoflurane-sparing effects of a high and a low dose of fentanyl in dogs, and its effects on mean arterial pressure (MAP) and heart rate (HR). Prospective, randomized crossover trial. Eight healthy male Beagle dogs weighing 12.1 ± 1.6 kg [mean ± standard deviation (SD)] and approximate age 1 year. Dogs were anesthetized using isoflurane and minimum alveolar concentration (MAC) was determined in duplicate by the bracketing method using an electrical stimulus on the tarsus. Animals were administered fentanyl: low dose (33 μg kg -1 loading dose, 0.2 μg kg -1  minute -1 ) or high dose (102 μg kg -1 loading dose, 0.8 μg kg -1  minute -1 ) and MAC was re-determined (MAC ISO-F ). Blood was collected for analysis of plasma fentanyl concentrations before administration and after MAC ISO-F determination. All values are presented as mean ± SD. Isoflurane MAC (MAC ISO ) was 1.30 ± 0.23% in the low dose treatment, which significantly decreased to 0.75 ± 0.22% (average MAC reduction 42.3 ± 9.4%). MAC ISO was 1.30 ± 0.18% in the high dose treatment, which significantly decreased to 0.30 ± 0.11% (average MAC reduction 76.9 ± 7.4%). Mean fentanyl plasma concentrations were 6.2 and 29.5 ng mL -1 for low and high dose treatments, respectively. MAP increased significantly only in the high dose treatment (from 81 ± 8 to 92 ± 9 mmHg). HR decreased significantly in both treatments from 108 ± 25 to 61 ± 14 beats minute -1 with the low dose and from 95 ± 14 to 42 ± 4 beats minute -1 with the high dose. Fentanyl administration resulted in a dose-dependent isoflurane MAC-sparing effect with bradycardia at both doses and an increase in MAP only at high dose. Further evaluation is needed to determine the effects of fentanyl on the overall cardiovascular function. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All

High concentration of Daunorubicin and Daunorubicinol in human malignant astrocytomas after systemic administration of liposomal Daunorubicin

NARCIS (Netherlands)

Albrecht, K. W.; de Witt Hamer, P. C.; Leenstra, S.; Bakker, P. J.; Beijnen, J. H.; Troost, D.; Kaaijk, P.; Bosch, A. D.

2001-01-01

The value of chemotherapy in patients with malignant astrocytoma remains controversial. In our laboratories in vitro experiments with organotypic spheroid cultures showed superior effectiveness of anthracyclines. Systemic administration did not provide in therapeutic concentrations so far. Because

A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration.

Science.gov (United States)

Sun, Changling; Wang, Xueling; Zheng, Zhaozhu; Chen, Dongye; Wang, Xiaoqin; Shi, Fuxin; Yu, Dehong; Wu, Hao

2015-01-01

This study aimed to investigate the sustained drug release properties and hearing protection effect of polyethylene glycol-coated polylactic acid (PEG-PLA) stealth nanoparticles loaded with dexamethasone (DEX). DEX was fabricated into PEG-PLA nanoparticles using an emulsion and evaporation technique, as previously reported. The DEX-loaded PEG-PLA nanoparticles (DEX-NPs) had a hydrodynamic diameter of 130±4.78 nm, and a zeta potential of -26.13±3.28 mV. The in vitro release of DEX from DEX-NPs lasted 24 days in phosphate buffered saline (pH 7.4), 5 days in artificial perilymph (pH 7.4), and 1 day in rat plasma. Coumarin 6-labeled NPs placed onto the round window membrane (RWM) of guinea pigs penetrated RWM quickly and accumulated to the organs of Corti, stria vascularis, and spiral ganglion cells after 1 hour of administration. The DEX-NPs locally applied onto the RWM of guinea pigs by a single-dose administration continuously released DEX in 48 hours, which was significantly longer than the free DEX that was cleared out within 12 hours after administration at the same dose. Further functional studies showed that locally administrated single-dose DEX-NPs effectively preserved outer hair cells in guinea pigs after cisplatin insult and thus significantly attenuated hearing loss at 4 kHz and 8 kHz frequencies when compared to the control of free DEX formulation. Histological analyses indicated that the administration of DEX-NPs did not induce local inflammatory responses. Therefore, prolonged delivery of DEX by PEG-PLA nanoparticles through local RWM diffusion (administration) significantly protected the hair cells and auditory function in guinea pigs from cisplatin toxicity, as determined at both histological and functional levels, suggesting the potential therapeutic benefits in clinical applications.

Pharmacokinetics and selected pharmacodynamics of trazodone following intravenous and oral administration to horses undergoing fitness training.

Science.gov (United States)

Knych, Heather K; Mama, Khursheed R; Steffey, Eugene P; Stanley, Scott D; Kass, Philip H

2017-10-01

OBJECTIVE To measure concentrations of trazodone and its major metabolite in plasma and urine after administration to healthy horses and concurrently assess selected physiologic and behavioral effects of the drug. ANIMALS 11 Thoroughbred horses enrolled in a fitness training program. PROCEDURES In a pilot investigation, 4 horses received trazodone IV (n = 2) or orally (2) to select a dose for the full study; 1 horse received a vehicle control treatment IV. For the full study, trazodone was initially administered IV (1.5 mg/kg) to 6 horses and subsequently given orally (4 mg/kg), with a 5-week washout period between treatments. Blood and urine samples were collected prior to drug administration and at multiple time points up to 48 hours afterward. Samples were analyzed for trazodone and metabolite concentrations, and pharmacokinetic parameters were determined; plasma drug concentrations following IV administration best fit a 3-compartment model. Behavioral and physiologic effects were assessed. RESULTS After IV administration, total clearance of trazodone was 6.85 ± 2.80 mL/min/kg, volume of distribution at steady state was 1.06 ± 0.07 L/kg, and elimination half-life was 8.58 ± 1.88 hours. Terminal phase half-life was 7.11 ± 1.70 hours after oral administration. Horses had signs of aggression and excitation, tremors, and ataxia at the highest IV dose (2 mg/kg) in the pilot investigation. After IV drug administration in the full study (1.5 mg/kg), horses were ataxic and had tremors; sedation was evident after oral administration. CONCLUSIONS AND CLINICAL RELEVANCE Administration of trazodone to horses elicited a wide range of effects. Additional study is warranted before clinical use of trazodone in horses can be recommended.

Comparison of 3-Factor Prothrombin Complex Concentrate and Low-Dose Recombinant Factor VIIa for Warfarin Reversal

OpenAIRE

Chapman, Scott A; Irwin, Eric D; Abou-Karam, Nada M; Rupnow, Nichole M; Hutson, Katherine E; Vespa, Jeffrey; Roach, Robert M

2014-01-01

Introduction Prothrombin complex concentrate (PCC) and recombinant Factor VIIa (rFVIIa) have been used for emergent reversal of warfarin anticoagulation. Few clinical studies have compared these agents in warfarin reversal. We compared warfarin reversal in patients who received either 3 factor PCC (PCC3) or low-dose rFVIIa (LDrFVIIa) for reversal of warfarin anticoagulation. Methods Data were collected from medical charts of patients who received at least one dose of PCC3 (20 units/kg) or LDr...

Dose conversion factors

International Nuclear Information System (INIS)

Kocher, D.C.; Eckerman, K.F.

1992-01-01

The following is discussed in this report: concepts and quantities used in calculating radiation dose from internal and external exposure. Tabulations of dose conversion factor for internal and external exposure to radionuclides. Dose conversion factors give dose per unit intake (internal) or dose per unit concentration in environment (external). Intakes of radionuclides for internal exposure and concentrations of radionuclides in environment for external exposure are assumed to be known. Intakes and concentrations are obtained, e.g., from analyses of environmental transport and exposure pathways. differences between dosimetry methods for radionuclides and hazardous chemicals are highlighted

Assessment of natural radioactivity concentrations and gamma dose levels around Shorapur, Karnataka

Energy Technology Data Exchange (ETDEWEB)

Rajesh, S.; Avinash, P.; Kerur, B. R., E-mail: kerurpbk@rediffmail.com.com [Department of Physics, Gulbarga University Kalaburagi – 585 106 India (India); Anilkumar, S. [Radiation Safety Systems Division, BARC, Mumbai - 400 085 (India)

2015-08-28

This study assesses the level of background radiation around Shorapur. The study region locates the western part of the Yadgir district of Karnataka. Shorapur and Shahapur talukas are mostly composed of clay, shale sandstone, granite rock and part of study area is black soil. Thirty sample locations were selected along the length and breadth of Shorapur and Shahapur taluka. Natural radionuclide activity concentrations in soil samples were determined using 4'X4' NaI (Tl) gamma spectroscopy. Outdoor gamma dose measurements in air at 1 m above ground level were determined using Rad Eye PRD survey meter. Estimated dose values are compared with the survey meter values and found to be good agreement between them and also with the data obtained from different other areas of Karnataka and India. The average values were found to be slightly higher in the present investigation.

Concentration of 222Rn in drinking water of the Zacatecas City, measured by liquid scintillation and associated dose

International Nuclear Information System (INIS)

Arevalo B, C. A.; Lopez del R, H.; Davila R, J. I.; Mireles G, F.; Pinedo V, J. L.; Rios M, C.; Saucedo A, S. A.

2017-09-01

A study was carried out to determine the concentration of 222 Rn in samples of drinking water collected from different homes in the Zacatecas city, Mexico, whose main source of supply is groundwater. The 222 Rn radioactive gas is a product of the decay series of 238 U and is considered one of the main sources of natural radiation, since it contributes almost half of the radiation dose that a person will receive throughout his life. The 222 Rn originates in the rocks of the aquifers and dissolves in the water, which is later integrated into the distribution network of the public supply that supplies the entire population. Exposure to ionizing radiation that 222 Rn and its offspring emit can damage the DNA molecule, inducing the possible appearance of cancer. Has been demonstrated by various epidemiological studies carried out in uranium mines workers in different parts of the world, that this exposure increases the incidence of lung cancer, placing 222 Rn and their offspring as the second main cause of this type of cancer, after smoking habit. Using the technique of solvent extraction of 222 Rn in water and liquid scintillation spectrometry, water collected from 14 different households was sampled and analyzed. The average of the measured activity of 222 Rn was 2.09 Bq/L and the annual effective dose per water intake attributable to that concentration of 6.07 mSv/a. The concentration of 222 Rn in water and the annual effective dose are below 11 Bq/L and 50 mSv/a, such concentrations are the maximum limits established by the Unites States Environmental Protection Agency (US EPA) and the ICRP, respectively. The concentration of 222 Rn that is transferred from the water to the air inside a house was also calculated and the radiation dose that this concentration causes by inhalation, being 0.209 Bq/m 3 and 1,463 μ Sv a, respectively. (Author)

Predictors of Inadequate Linezolid Concentrations after Standard Dosing in Critically Ill Patients.

Science.gov (United States)

Taubert, Max; Zoller, Michael; Maier, Barbara; Frechen, Sebastian; Scharf, Christina; Holdt, Lesca-Miriam; Frey, Lorenz; Vogeser, Michael; Fuhr, Uwe; Zander, Johannes

2016-09-01

Adequate linezolid blood concentrations have been shown to be associated with an improved clinical outcome. Our goal was to assess new predictors of inadequate linezolid concentrations often observed in critically ill patients. Fifty-two critically ill patients with severe infections receiving standard dosing of linezolid participated in this prospective observational study. Serum samples (median, 32 per patient) were taken on four consecutive days, and total linezolid concentrations were quantified. Covariates influencing linezolid pharmacokinetics were identified by multivariate analysis and a population pharmacokinetic model. Target attainment (area under the concentration-time curve over 12 h [AUC12]/MIC ratio of >50; MIC = 2 mg/liter) was calculated for both the study patients and a simulated independent patient group (n = 67,000). Target attainment was observed for only 36% of the population on both days 1 and 4. Independent covariates related to significant decreases of linezolid concentrations included higher weight, creatinine clearance rates, and fibrinogen and antithrombin concentrations, lower concentrations of lactate, and the presence of acute respiratory distress syndrome (ARDS). Linezolid clearance was increased in ARDS patients (by 82%) and in patients with elevated fibrinogen or decreased lactate concentrations. In simulated patients, most covariates, including fibrinogen and lactate concentrations and weight, showed quantitatively minor effects on target attainment (difference of ≤9% between the first and fourth quartiles of the respective parameters). In contrast, the presence of ARDS had the strongest influence, with only ≤6% of simulated patients reaching this target. In conclusion, the presence of ARDS was identified as a new and strong predictor of insufficient linezolid concentrations, which might cause treatment failure. Insufficient concentrations might also be a major problem in patients with combined alterations of other covariate

Dose response characterization of the association of serum digoxin concentration with mortality outcomes in the Digitalis Investigation Group trial

NARCIS (Netherlands)

Adams, Kirkwood F.; Butler, Javed; Patterson, J. Herbert; Stough, Wendy Gattis; Bauman, Jerry L.; van Veldhuisen, Dirk J.; Schwartz, Todd A.; Sabbah, Hani; Mackowiak, John I.; Ventura, Hector O.; Ghali, Jalal K.

AimsMany patients with heart failure and reduced EF remain at high risk for hospitalization despite evidence-based therapy. Digoxin may decrease hospitalization; however, uncertainty persists concerning its proper administration and effect on mortality. This study investigated whether using dose

Oxycodone physical dependence and its oral self-administration in C57BL/6J mice.

Science.gov (United States)

Enga, Rachel M; Jackson, Asti; Damaj, M Imad; Beardsley, Patrick M

2016-10-15

Abuse of prescription opioids, such as oxycodone, has markedly increased in recent decades. While oxycodone's antinociceptive effects have been detailed in several preclinical reports, surprisingly few preclinical reports have elaborated its abuse-related effects. This is particularly surprising given that oxycodone has been in clinical use since 1917. In a novel oral operant self-administration procedure, C57BL/6J mice were trained to self-administer water before introducing increasing concentrations of oxycodone (0.056-1.0mg/ml) under post-prandial conditions during daily, 3-h test sessions. As the concentration of oxycodone increased, the numbers of deliveries first increased, then decreased in an inverted U-shape fashion characteristic of the patterns of other drugs self-administered during limited access conditions. After post-prandial conditions were removed, self-administration at the highest concentration was maintained suggesting oral oxycodone served as a positive reinforcer. In other mice, using a novel regimen of physical dependence, mice were administered increasing doses of oxycodone (9.0-33.0mg/kg, s.c.) over 9 days, challenged with naloxone (0.1-10.0mg/kg, s.c.), and then observed for 30min. Naloxone dose-dependently increased the observed number of somatic signs of withdrawal, suggesting physical dependence of oxycodone was induced under this regimen. This is the first report demonstrating induction of oral operant self-administration of oxycodone and dose-dependent precipitations of oxycodone withdrawal in C57BL/6J mice. The use of oral operant self-administration as well as the novel physical dependence regimen provides useful approaches to further examine the abuse- and dependence-related effects of this highly abused prescription opioid. Copyright © 2016 Elsevier B.V. All rights reserved.

Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation

OpenAIRE

Frank, N.; Hermida, P.; Sanchez?Londo?o, A.; Singh, R.; Gradil, C.M.; Uricchio, C.K.

2017-01-01

Background Octreotide is a somatostatin analog that suppresses insulin secretion. Hypothesis We hypothesized that octreotide would suppress insulin concentrations in horses and that normal (N) horses and those with insulin dysregulation (ID) would differ significantly in their plasma glucose and insulin responses to administration of octreotide. Animals Twelve horses, N = 5, ID = 7. Methods Prospective study. An oral sugar test was performed to assign horses to N and ID groups. Octreotide (1....

Systematic literature review of hospital medication administration errors in children

Directory of Open Access Journals (Sweden)

Ameer A

2015-11-01

Full Text Available Ahmed Ameer,1 Soraya Dhillon,1 Mark J Peters,2 Maisoon Ghaleb11Department of Pharmacy, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK; 2Paediatric Intensive Care Unit, Great Ormond Street Hospital, London, UK Objective: Medication administration is the last step in the medication process. It can act as a safety net to prevent unintended harm to patients if detected. However, medication administration errors (MAEs during this process have been documented and thought to be preventable. In pediatric medicine, doses are usually administered based on the child's weight or body surface area. This in turn increases the risk of drug miscalculations and therefore MAEs. The aim of this review is to report MAEs occurring in pediatric inpatients. Methods: Twelve bibliographic databases were searched for studies published between January 2000 and February 2015 using “medication administration errors”, “hospital”, and “children” related terminologies. Handsearching of relevant publications was also carried out. A second reviewer screened articles for eligibility and quality in accordance with the inclusion/exclusion criteria. Key findings: A total of 44 studies were systematically reviewed. MAEs were generally defined as a deviation of dose given from that prescribed; this included omitted doses and administration at the wrong time. Hospital MAEs in children accounted for a mean of 50% of all reported medication error reports (n=12,588. It was also identified in a mean of 29% of doses observed (n=8,894. The most prevalent type of MAEs related to preparation, infusion rate, dose, and time. This review has identified five types of interventions to reduce hospital MAEs in children: barcode medicine administration, electronic prescribing, education, use of smart pumps, and standard concentration. Conclusion: This review has identified a wide variation in the prevalence of hospital MAEs in children. This is attributed to

Pharmacokinetics of Levetiracetam in Healthy Hispaniolan Amazon Parrots ( Amazona ventralis ) After Oral Administration of a Single Dose.

Science.gov (United States)

Schnellbacher, Rodney; Beaufrère, Hugues; Vet, Dr Med; Arnold, Robert D; Tully, Thomas N; Mayer, Joerg; Divers, Stephen J

2014-09-01

Long-term anticonvulsive treatments have been poorly described in birds, and few pharmacokinetic studies have been performed, with mixed results. Levetiracetam, a new anticonvulsive drug, has shown good efficacy for monotherapy or adjunctive treatment of seizures in both human and veterinary medicine. To determine pharmacokinetics of levetiracetam in Hispaniolan Amazon parrots ( Amazona ventralis ), 20 healthy birds were randomly divided into 2 groups and administered either a 50 mg/kg (n = 10) or a 100 mg/kg (n = 10) oral dose of levetiracetam with no observable adverse effects. Blood samples were collected at baseline and at 12 time intervals (6 per group) for 16 hours. The concentration-time profiles resembled characteristic absorption, with maximum plasma concentrations of 61.0 μg/mL and 95.1 μg/mL at 60 minutes; terminal half-lives at 2.38 and 2.37 hours; volumes of distribution of 0.807 and 0.773 L/kg, with an area under the curve at 14 100 and 28 820 mg × min/L; and clearance rates of 3.65 and 3.60 mL/min per kg, respectively. Plasma concentrations were greater than 5.5 mg/L for up to 9.4 and 12 hours, suggesting an 8- and 12-hour oral dosing at 50 and 100 mg/kg, respectively, would be sufficient to maintain targeted values. Clinically, doses and frequencies may need escalation based on differences in species and individuals, and drug levels should be monitored.

Excretion of radionuclides in human breast milk following administration of 125I-fibrinogen, 99Tc/sup m/-MAA and 51Cr-EDTA

International Nuclear Information System (INIS)

Mattsson, S.; Johansson, L.; Nosslin, B.; Ahlgren, L.

1981-01-01

Very few biokinetic and dosimetric data for estimating the absorbed dose to a breast-feeding child are available in the literature. The few available are usually case reports. We have measured the activity concentration in breast milk from one patient after administration of 125 I-fibrinogen, from two patients after administration of 99 Tc/sup m/-macroaggregated albumin, and from one patient after administration of 51 Cr-EDTA. We have compared our data with earlier published results and estimated the absorbed dose to the breast-feeding child using biokinetic data presented in this work and recently published S-values for new-born children

Radiation-induced strand-breaks and DNA-protein crosslinks depend predominantly on the dose, oxygen concentration and repair time

International Nuclear Information System (INIS)

Wheeler, K.T.; Miyagi, Y.; Zhang, H.

1995-01-01

It has been known for many years that the DNA damage produced by ionizing radiation depends upon the oxygen concentration around the DNA. For example, the number of DNA strand-breaks (SBs) formed per unit dose decreases at low oxygen concentrations, and the number of DNA-protein crosslinks formed per unit dose increases at low oxygen concentrations. If radiation-induced SBs and DPCs are to be useful for detecting and/or quantifying hypoxic cells in solid tumors, the formation of these lesions must depend predominantly on the oxygen concentration around the DNA. All other physical, biological, and physiological factors must either be controllable or have little influence on the assay used to measure these lesions. This paper is a summary of the authors' recent experiments to determine if the radiation-induced SBs and DPCs measured by alkaline elution may be used to estimate the hypoxic fraction or fractional hypoxic volume of solid tumors

Pharmacokinetics of butorphanol after intravenous, intramuscular, and oral administration in Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Guzman, David Sanchez-Migallon; Flammer, Keven; Paul-Murphy, Joanne R; Barker, Steven A; Tully, Thomas N

2011-09-01

Previous studies have validated the clinical use of opioids with kaap-receptor affinities for pain management in birds. Butorphanol, a kappa opioid receptor agonist and a mu opioid receptor antagonist, is currently considered by many clinicians to be the opioid of choice for this use. However, despite studies reporting the analgesic properties of butorphanol in psittacine birds, dosing intervals have not been established for any psittacine species. The goals of this study in the Hispaniolan Amazon parrot (Amazona ventralis) were to evaluate the pharmacokinetics of butorphanol tartrate after intravenous (IV), intramuscular (IM), and oral (PO) administration and to determine the bioavailability of butorphanol tartrate after oral administration. Twelve Hispaniolan Amazon parrots were used in the study, with a complete-crossover experimental design and a 3-month period separating each part of the study. The birds were randomly assigned to 3 groups (n = 4) for each stage. Butorphanol tartrate was administered once at a dose of 5 mg/kg in the basilic vein or pectoral muscles or as an oral solution delivered via feeding tube into the crop for the IV, IM, and PO studies, respectively. After butorphanol administration, blood samples were collected at 1, 5, 15, 30, 60, 90, 120, 180, and 240 minutes for the IV and IM studies and at 5, 15, 30, 60, 90, 120, 180, 240, and 300 minutes for the PO study. Because of the size limitation of the birds, naive pooling of datum points was used to generate a mean plasma butorphanol concentration at each time point. For each study, birds in each group (n = 4) were bled 3 times after dosing. Plasma butorphanol concentrations were determined by high-performance liquid chromatography/tandem mass spectrometry, and pharmacokinetic parameters were calculated. Butorphanol tartrate was found to have high bioavailability and rapid elimination following IM administration. In contrast, oral administration resulted in low bioavailability (Amazon

Estimates concentrations in bottled 222Rn of the dose due to mineral waters in Iran

International Nuclear Information System (INIS)

Assadi, M. R.; Esmaealnejad, M.; Rahmatinejad, Z.

2006-01-01

Radon is a radionuclide that has the main role in exposure. Radon in water causes exposure in whole body but the largest dose being received by the stomach, as EPA (Environmental Protection Agency) estimates that radon in drinking water causes about 168 cancer deaths per year: 89 p ercent f rom lung cancer caused by breathing released to the indoor air from water and 11 p ercent f rom stomach cancer caused by consuming water containing radon. Now days the consumption of bottled mineral waters has become very popular. As is known, some kinds of mineral waters contain naturally occurring radionuclides in higher concentration than the usual drinking (tap) water. Surveys and reports on radon in most surface waters is low compared with radon level in groundwater and mineral water. In our work, the concentration of Rn(222) was determined in some bottled mineral waters available in Iran , and in next step the dose contribution ; due to ingestion ; for 1 l d -1 bottled mineral water consumption.

Bioavailability of diclofenac potassium at low doses

Science.gov (United States)

Hinz, Burkhard; Chevts, Julia; Renner, Bertold; Wuttke, Henrike; Rau, Thomas; Schmidt, Andreas; Szelenyi, Istvan; Brune, Kay; Werner, Ulrike

2005-01-01

Aim Diclofenac-K has been recently launched at low oral doses in different countries for over-the-counter use. However, given the considerable first-pass metabolism of diclofenac, the degree of absorption of diclofenac-K at low doses remained to be determined. The aim of this study was to determine the bioavailability of low-dose diclofenac-K. Methods A randomized, three-way, cross-over study was performed in 10 subjects. Each received diclofenac-K, 22.5 mg via short-term i.v. infusion and orally at single doses of 12.5 mg and 25 mg. Results Mean (± SD) times to maximal plasma concentration (tmax) of diclofenac were 0.48 ± 0.28 h (12.5 mg) and 0.93 ± 0.96 h (25 mg). The absolute bioavailability of diclofenac-K after oral administration did not differ significantly in the 12.5-mg and 25-mg dose group (63.1 ± 12.6% vs. 65.1 ± 19.4%, respectively). The 90% confidence intervals for the AUC∞ and AUCt ratios for the two oral regimes were 82.6, 103.4% (point estimate 92.4%) and 86.2, 112.9% (point estimate 98.6%), respectively. These values were within the acceptance criteria for bioequivalence (80–125%). Conclusions Our data indicate that diclofenac-K is rapidly and well absorbed at low dose, and are consistent with a rapid onset of action of the drug. Abbreviations AUC, area under plasma concentraton-time curve; Cmax, peak plasma concentration; CI, confidence interval; COX, cyclooxygenase; D, dose; F, absolute bioavailability; tmax, time to reach Cmax. PMID:15606444

Systemic effects of low-dose dopamine during administration of cytarabine.

Science.gov (United States)

Connelly, James; Benani, Dina J; Newman, Matthew; Burton, Bradley; Crow, Jessica; Levis, Mark

2017-09-01

Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m 2 /dose or greater, with or without dopamine at ≤5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low-dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function.

Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone in normal volunteers.

Science.gov (United States)

Jung, Caroline; Greco, Santo; Nguyen, Hanh H T; Ho, Jui T; Lewis, John G; Torpy, David J; Inder, Warrick J

2014-11-26

Glucocorticoid replacement is essential in patients with primary and secondary adrenal insufficiency, but many patients remain on higher than recommended dose regimens. There is no uniformly accepted method to monitor the dose in individual patients. We have compared cortisol concentrations in plasma, saliva and urine achieved following "physiological" and "stress" doses of hydrocortisone as potential methods for monitoring glucocorticoid replacement. Cortisol profiles were measured in plasma, saliva and urine following "physiological" (20 mg oral) or "stress" (50 mg intravenous) doses of hydrocortisone in dexamethasone-suppressed healthy subjects (8 in each group), compared to endogenous cortisol levels (12 subjects). Total plasma cortisol was measured half-hourly, and salivary cortisol and urinary cortisol:creatinine ratio were measured hourly from time 0 (between 0830 and 0900) to 5 h. Endogenous plasma corticosteroid-binding globulin (CBG) levels were measured at time 0 and 5 h, and hourly from time 0 to 5 h following administration of oral or intravenous hydrocortisone. Plasma free cortisol was calculated using Coolens' equation. Plasma, salivary and urine cortisol at 2 h after oral hydrocortisone gave a good indication of peak cortisol concentrations, which were uniformly supraphysiological. Intravenous hydrocortisone administration achieved very high 30 minute cortisol concentrations. Total plasma cortisol correlated significantly with both saliva and urine cortisol after oral and intravenous hydrocortisone (P cortisol and urinary cortisol:creatinine ratio may provide useful alternatives to plasma cortisol measurements to monitor replacement doses in hypoadrenal patients.

Radiation dose to workers due to the inhalation of dust during granite fabrication

International Nuclear Information System (INIS)

Zwack, L M; Stewart, J H; McCarthy, J F; Allen, J G; McCarthy, W B

2014-01-01

There has been very little research conducted to determine internal radiation doses resulting from worker exposure to ionising radiation in granite fabrication shops. To address this issue, we estimated the effective radiation dose of granite workers in US fabrication shops who were exposed to the maximum respirable dust and silica concentrations allowed under current US regulations, and also to concentrations reported in the literature. Radiation doses were calculated using standard methods developed by the International Commission on Radiological Protection. The calculated internal doses were very low, and below both US occupational standards (50 mSv yr −1 ) and limits applicable to the general public (1 mSv yr −1 ). Workers exposed to respirable granite dust concentrations at the US Occupational Safety and Health Administration (OSHA) respirable dust permissible exposure limit (PEL) of 5 mg m −3 over a full year had an estimated radiation dose of 0.062 mSv yr −1 . Workers exposed to respirable granite dust concentrations at the OSHA silica PEL and at the American Conference of Governmental Industrial Hygienists Threshold Limit Value for a full year had expected radiation doses of 0.007 mSv yr −1 and 0.002 mSv yr −1 , respectively. Using data from studies of respirable granite dust and silica concentrations measured in granite fabrication shops, we calculated median expected radiation doses that ranged from <0.001 to 0.101 mSv yr −1 . (paper)

Clinical study of a new therapy for nerve agent poisoning: Ascending dose tolerance study of HI-6 + atropine

Energy Technology Data Exchange (ETDEWEB)

Clement, J.G.; Bailey, D.G.; Madill, H.D.; Spence, J.D.

1993-05-13

HI-6 was rapidly absorbed from an IM injection site. Maximum HI-6 plasma concentrations of 1.88, 4.96, 8.31 15.0 ug/ml were found 28-36 min after administration and maintained above 4 ug/ml concentration for 0, 39, 112 172.5 min following administration of 62.5, 125, 250 or 500 mg HI-6 + atropine (2 mg), respectively. The calculated half life of HI-6 was 78.2 min following 62.5 mg HI-6 + atropine dose and approximately 64-67 min following 125-500 mg HI-6 + atropine doses. Approximately 50 % of the total dose of HI-6 was eliminated unchanged in the urine. There were significant changes (p < 0.05) in AST, CPK, creatinine and gamma GT following the 500 mg HI-6 + atropine dose but they were not considered to be clinically significant. Urinalysis, hematology and semen analysis over the 24 hr observation period was uneventful. There were no clinically significant changes in heart rate or ECG trace, respiration or blood pressure, visual and mental acuity following HI-6 + atropine.

Comparison of the pharmacokinetics of imipenem after intravenous and intrathecal administration in rabbits.

Science.gov (United States)

Wang, Y; Qiu, L; Dong, J; Wang, B; Shi, Z; Liu, B; Wang, W; Zhang, J; Cai, S; Ye, G; Cai, X

2013-03-01

Intrathecal administration of antibiotics has potentially high effectiveness for the treatment for severe intracranial infections, particularly nosocomial meningitis. The use of intrathecal injection of antibiotics has been reported mostly in case reports. However, there is sparse data regarding the pharmacokinetics of antibiotics after intrathecal administration. This study investigated whether intrathecal injection is an effective method for the administration of imipenem. The pharmacokinetics of imipenem after intrathecal and intravenous administration of 1:1 imipenem: cilastatin (IMI/CIL) to rabbits were compared. The AUC0-t in the cerebrospinal fluid for intrathecal administration was approximately twice that of an equal dose of intravenous administration at doses of 0.35, 0.7, and 1.4 mg/kg. Brain concentrations of imipenem after intrathecal injection were three times greater than observed after intravenous injection and remained high for at least 8 hours post-injection. Elimination of imipenem after administration by either route was primarily via urine, but a transient surge of imipenem in bile and intestinal tissue was observed. Results indicate that there is a clinical potential for intrathecally administered IMI/CIL. Further studies are warranted to investigate the potential for seizure and to assess the translatability of the rabbit model to human treatment.

Doses to the hand during the administration of radiolabeled antibodies containing Y-90, Tc-99m, I-131, and Lu-177

Energy Technology Data Exchange (ETDEWEB)

Barber, D.E. [Minnesota Univ., Minneapolis, MN (United States). School of Public Health; Carsten, A.L.; Kaurin, D.G.L.; Baum, J.W. [Brookhaven National Lab., Upton, NY (United States)

1997-02-01

Exposure of the hands of medical personnel administering radiolabeled antibodies (RABs) was evaluated on the basis of (a) observing and photo-documenting administration techniques, and (b) experimental data on doses to thermoluminescent dosimeters (TLDs) on fingers of phantom hands holding syringes, and on syringes, with radionuclides in the syringes in each case. Actual exposure data for I-131 and Lu-177 were obtained in field studies. Variations in handling and administration techniques were identified. Dose rates measured using TLDs on the surface of loaded syringes were adjusted for differences in electronic stopping power, absorption coefficients, and attenuation between dosimeters and tissue to estimate dose-to-skin averaged over 1 cm{sup 2} at 7 mg cm{sup {minus}2} depth for Y-90, Tc-99m, I-131, and Lu-177. Dose rate coefficients to the skin, if in contact with the syringe wall, were 89, 1.9, 3.8, and 0.41 {micro}Sv s{sup {minus}1} per 37 MBq (1 mCi) for Y-90, Tc-99m, I-131, and Lu-177, respectively. For dose reduction, when using Y-90 the importance was clearly indicated of (a) avoiding direct contact with syringes containing RABs, if practical, and (b) using a beta-particle shield on the syringe. In using a syringe for injection, doses can best be approximated for the geometry studied by (a) wearing a finger dosimeter on the middle finger, toward the outside of the hand, on the hand operating the plunger, and (b) wearing finger dosimeters on the inner (palm) side of the finger on the hand that supports the syringe for energetic beta-particle emitters, such as Y-90 and Re-188.

Doses to the hand during the administration of radiolabeled antibodies containing Y-90, Tc-99m, I-131, and Lu-177

International Nuclear Information System (INIS)

Barber, D.E.

1997-02-01

Exposure of the hands of medical personnel administering radiolabeled antibodies (RABs) was evaluated on the basis of (a) observing and photo-documenting administration techniques, and (b) experimental data on doses to thermoluminescent dosimeters (TLDs) on fingers of phantom hands holding syringes, and on syringes, with radionuclides in the syringes in each case. Actual exposure data for I-131 and Lu-177 were obtained in field studies. Variations in handling and administration techniques were identified. Dose rates measured using TLDs on the surface of loaded syringes were adjusted for differences in electronic stopping power, absorption coefficients, and attenuation between dosimeters and tissue to estimate dose-to-skin averaged over 1 cm 2 at 7 mg cm -2 depth for Y-90, Tc-99m, I-131, and Lu-177. Dose rate coefficients to the skin, if in contact with the syringe wall, were 89, 1.9, 3.8, and 0.41 microSv s -1 per 37 MBq (1 mCi) for Y-90, Tc-99m, I-131, and Lu-177, respectively. For dose reduction, when using Y-90 the importance was clearly indicated of (a) avoiding direct contact with syringes containing RABs, if practical, and (b) using a beta-particle shield on the syringe. In using a syringe for injection, doses can best be approximated for the geometry studied by (a) wearing a finger dosimeter on the middle finger, toward the outside of the hand, on the hand operating the plunger, and (b) wearing finger dosimeters on the inner (palm) side of the finger on the hand that supports the syringe for energetic beta-particle emitters, such as Y-90 and Re-188

Concentration activities of natural radionuclides in three fish species in Brazilian coast and their contributions to the absorbed doses

International Nuclear Information System (INIS)

Pereira, Wagner de S.; Py Junior, Delcy de A.; Kelecom, Alphonse

2009-01-01

Activity concentrations of U-238, Ra-226, Pb-210, Th-232 e Ra-228 were analysed in three fish species at the Brasilian Coast. The fish 'Cubera snapper' (Lutjanus cyanopterus, Cuvier, 1828), in the region of Ceara and 'Whitemouth croaker' (Micropogonias furnieri, Desmarest, 1823) and 'Lebranche mullet' (Mugil liza, Valenciennes, 1836) in the region of Rio de Janeiro. These concentrations were transformed in absorbed dose rate using a dose conversion factor in unit of gray per year (μGy y -1 ), per becquerel per kilogram (Bq kg -1 ). Only the absorbed dose due to intake of radionuclides was examined, and the contributions due to radionuclides present in water and sediment were disregarded. The radionuclides were considered to be uniformly distributed in the fish body. The limit of the dose rate used, proposed by the Department of Energy of the USA, is equal to 3.65 10 03 mGy y -1 . The average dose rate due to the studied radionuclides is equal to 6.09 10 00 μGy y -1 , a value minor than 0.1% than the limits indicated by DOE, and quite similar to that found in the literature for 'benthic' fish. The most important radionuclides were the alpha emitters Ra-226 having 61 % of absorbed dose rate. U-238 and Th-232, each contributes with approximately 20 % of the absorbed dose rate. These three radionuclides are responsible for almost 100% of the dose rate received by the studied organisms. The beta emitters Ra-228 and Pb-210 account for approximately 1 % of the absorbed dose rate. (author)

Studying the effect of administration route and treatment dose on the selection of enrofloxacin resistance in commensal Escherichia coli in broilers.

Science.gov (United States)

Chantziaras, Ilias; Smet, Annemieke; Haesebrouck, Freddy; Boyen, Filip; Dewulf, Jeroen

2017-07-01

Factors potentially contributing to fluoroquinolone resistance selection in commensal Escherichia coli strains in poultry were studied through a series of in vivo experiments. The effect of the initial prevalence of enrofloxacin resistance in the E. coli gut microbiota, effect of the bacterial fitness of the enrofloxacin-resistant strain and effect of treatment with enrofloxacin (effect of dose and effect of route of administration) were assessed. Four in vivo studies with broiler chickens were performed. Right after hatching, the chicks were inoculated with either a bacteriologically fit or a bacteriologically non-fit fluoroquinolone-resistant strain as either a minority or the majority of the total E. coli population. Six days later, the chicks were treated for three consecutive days either orally or parenterally and using three different doses (under-, correct- and over-dose) of enrofloxacin. The faecal shedding of E. coli strains was quantified by plating on agar plates either supplemented or not supplemented with enrofloxacin. Linear mixed models were used to assess the effect of the aforementioned variables on the selection of enrofloxacin resistance. The factors that significantly contributed were treatment ( P  <   0.001), bacterial fitness of the resistant donor strain ( P  <   0.001), administration route ( P  =   0.052) and interactions between bacterial fitness and administration route ( P  <   0.001). In the currently used models, fluoroquinolone resistance selection was influenced by treatment, bacterial fitness of the inoculation strain and administration route. The use of oral treatment seems to select more for fluoroquinolone resistance, particularly in the model where a non-fit strain was used for inoculation. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis.

Science.gov (United States)

Mogensen, Stine; Sverrisdóttir, Eva; Sveinsdóttir, Kolbrún; Treldal, Charlotte; Jensen, Kenneth; Jensen, Anders Bonde; Kristensen, Claus Andrup; Jacobsen, Jette; Kreilgaard, Mads; Petersen, Janne; Andersen, Ove

2017-01-01

The aim was to investigate systemic exposure after administration of a novel bupivacaine lozenge in healthy individuals with normal mucosa and in head and neck cancer (HNC) patients with oral mucositis. A lozenge containing 5, 10, 25 and 50 mg bupivacaine, respectively, was administered as single dose to 10 healthy individuals, and a lozenge containing 25 mg bupivacaine was administered as single dose to 10 HNC patients with oral mucositis and as multiple doses to five patients with HNC. Blood samples were collected for 6 hr from the healthy individuals and 3 hr from the patients with HNC, respectively, after administration. The plasma concentration-time profiles of bupivacaine were fitted to pharmacokinetic models using nonlinear mixed-effects modelling, evaluating demographics and health status as covariates. The population pharmacokinetics (PK) of bupivacaine lozenge was best described by a two-compartment distribution model with absorption transit compartments. All the observed plasma concentrations were well below the bupivacaine concentrations (2000-2250 ng/ml) which have caused toxic symptoms. The PK model suggested that relative bioavailability was two times higher in HNC patients with oral mucositis grade 1-2 and three times higher in HNC patients with oral mucositis grade 3-4 than in the healthy individuals. Simulations showed that the plasma concentrations would be below the toxic limit after repeated dosing every second hour with 25 mg bupivacaine for five days. The 25-mg bupivacaine lozenges were safe without systemic toxic levels of bupivacaine or risk of side effects. Based on PK simulations of repeated doses of 25 mg every two hours for 16 hr a day, the lozenges can be administered with minimum risk of exceeding the toxic limit. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects.

Science.gov (United States)

Suriyo, Tawit; Pholphana, Nanthanit; Ungtrakul, Teerapat; Rangkadilok, Nuchanart; Panomvana, Duangchit; Thiantanawat, Apinya; Pongpun, Wanwisa; Satayavivad, Jutamaad

2017-06-01

Andrographis paniculata has been widely used in Scandinavian and Asian counties for the treatment of the common cold, fever, and noninfectious diarrhea. The present study was carried out to investigate the physiological effects of short-term multiple dose administration of a standardized A. paniculata capsule used for treatment of the common cold and uncomplicated upper respiratory tract infections, including blood pressure, electrocardiogram, blood chemistry, hematological profiles, urinalysis, and blood coagulation in healthy Thai subjects. Twenty healthy subjects (10 males and 10 females) received 12 capsules per day orally of 4.2 g of a standardized A. paniculata crude powder (4 capsules of 1.4 g of A. paniculata , 3 times per day, 8 h intervals) for 3 consecutive days. The results showed that all of the measured clinical parameters were found to be within normal ranges for a healthy person. However, modulation of some parameters was observed after the third day of treatment, for example, inductions of white blood cells and absolute neutrophil count in the blood, a reduction of plasma alkaline phosphatase, and an induction of urine pH. A rapid and transient reduction in blood pressure was observed at 30 min after capsule administration, resulting in a significant reduction of mean systolic blood pressure. There were no serious adverse events observed in the subjects during the treatment period. In conclusion, this study suggests that multiple oral dosing of A. paniculata at the normal therapeutic dose for the common cold and uncomplicated upper respiratory tract infections modulates various clinical parameters within normal ranges for a healthy person. Georg Thieme Verlag KG Stuttgart · New York.

Zolpidem prescribing practices before and after Food and Drug Administration required product labeling changes

OpenAIRE

Norman, Jessica L; Fixen, Danielle R; Saseen, Joseph J; Saba, Laura M; Linnebur, Sunny A

2017-01-01

Background: Women have higher morning serum zolpidem concentrations than men after taking an evening dose, potentially leading to increased risk of harm. On 19 April 2013, the United States Food and Drug Administration required labeling changes for zolpidem, recommending an initial dose of no greater than 5 mg (immediate release) or 6.25 mg (controlled release) per night in women. Objectives: The primary objective of this study was to compare prescribing practices before and after the 2013 zo...

Polonium-210 concentration of cigarettes traded in Cuba and their estimated dose contribution due to smoking

International Nuclear Information System (INIS)

Brigido Flores, O.; Montalvan Estrada, A.; Fabelo Bonet, O.; Barreras Caballero, A.

2015-01-01

Cigarette smoking is one of the pathways that might contribute significantly to the increase in the radiation dose reaching man, due to the relatively large concentrations of polonium-210 found in tobacco leaves. The results of 200 Po determination on the 11 most frequently smoked brands of cigarettes and cigars which constitute over 75% of the total cigarette consumption in Cuba are presented and discussed. Moreover, the polonium content in cigarette smoke was estimated on the basis of its activity in cigarettes, ash, fresh filters and post-smoking filters. 210 Po was determined by gas flow proportional detector after spontaneous deposition of 210 Po on a high copper-content disk. The annual committed equivalent dose for lungs and the annual effective dose for smokers between 12-17 years old and for adults were calculated on the basis of the 210 Po inhalation through cigarette smoke. The results showed concentration ranging from 9.3 to 14.4 mBq per cigarette with a mean value of 11.8 ± 0.6 mBq.Cig -1 . the results of this work indicate that Cuban smokers who smoke one pack (20 cigarettes) per day inhale from 62 to 98 mBq.d -1 of 210 Po and smokers between 12-17 years old who consume 10 cigarettes daily inhale from 30-50 mBq.d -1 . The average committed equivalent dose for lungs is estimated to be 466 ± 36 and 780 ± 60 μSv.year -1 for young and adult smokers, respectively and annual committed effective dose is calculated to be 60 ± 5 and 100 ± 8 μSv for these two groups of smokers, respectively. (Author)

Pharmacokinetic evaluation of novel midazolam gel formulations following buccal administration to healthy dogs.

Science.gov (United States)

Aldawsari, Mohammed F; Lau, Vivian W; Babu, Ramapuram J; Arnold, Robert D; Platt, Simon R

2018-01-01

OBJECTIVE To determine the physiochemical properties and pharmacokinetics of 3 midazolam gel formulations following buccal administration to dogs. ANIMALS 5 healthy adult hounds. PROCEDURES In phase 1 of a 2-phase study, 2 gel formulations were developed that contained 1% midazolam in a poloxamer 407 (P1) or hydroxypropyl methylcellulose (H1) base and underwent rheological and in vitro release analyses. Each formulation was buccally administered to 5 dogs such that 0.3 mg of midazolam/kg was delivered. Each dog also received midazolam hydrochloride (0.3 mg/kg, IV). There was a 3-day interval between treatments. Blood samples were collected immediately before and at predetermined times for 8 hours after drug administration for determination of plasma midazolam concentration and pharmacokinetic analysis. During phase 2, a gel containing 2% midazolam in a hydroxypropyl methylcellulose base (H2) was developed on the basis of phase 1 results. That gel was buccally administered such that midazolam doses of 0.3 and 0.6 mg/kg were delivered. Each dog also received midazolam (0.3 mg/kg, IV). All posttreatment procedures were the same as those for phase 1. RESULTS The H1 and H2 formulations had lower viscosity, greater bioavailability, and peak plasma midazolam concentrations that were approximately 2-fold as high, compared with those for the P1 formulation. The mean peak plasma midazolam concentration for the H2 formulation was 187.0 and 106.3 ng/mL when the midazolam dose administered was 0.6 and 0.3 mg/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that buccal administration of gel formulations might be a viable alternative for midazolam administration to dogs.

Beneficial effects of low dose Musa paradisiaca on the semen quality of male Wistar rats.

Science.gov (United States)

Alabi, A S; Omotoso, Gabriel O; Enaibe, B U; Akinola, O B; Tagoe, C N B

2013-03-01

This study aimed at determining the effects of administration of mature green fruits of Musa paradisiaca on the semen quality of adult male Wistar rats. THE ANIMALS USED FOR THE STUDY WERE GROUPED INTO THREE: the control group, given 2 ml of double distilled water, a low dose group given 500 mg/kg/day and a high dose group given 1000 mg/kg/day of the plantain fruits, which was made into flour, and dissolved in 2 ml of double distilled water for easy oral administration. Significant increment in the semen parameters was noticed in animals that received a lower dose of the plantain flour, but those animals who received the high dose had marked and very significant reduction in sperm cell concentration and percentage of morphologically normal spermatozoa. Musa paradisiaca should be consumed in moderate quantities in order to derive its beneficial effects of enhancing male reproductive functions.

Estimative of alpha radiation dose due to natural concentration of Ra-226 in waters from Pocos de Caldas

International Nuclear Information System (INIS)

Sigaud, G.M.

1979-01-01

A dosimetric model for calculating the annual dose equivalent for an individual and the annual collective dose equivalent from 226 Ra is developed. This model is applied to the measured concentrations of 226 Ra in waters of the hydro graphic basins of the Pocos de Caldas plateau, using the pathways of drinking water and ingestion of food grown in irrigated fields. A linear model for simulating potential 226 Ra contamination of the waters of the region is also applied, and the doses from these contaminations are estimated using the dosimetric model developed. (author)

Single dose pharmacokinetics of fenspiride hydrochloride: phase I clinical trial.

Science.gov (United States)

Montes, B; Catalan, M; Roces, A; Jeanniot, J P; Honorato, J M

1993-01-01

The absolute bioavailability of fenspiride has been studied in twelve healthy volunteers. It was administered IV and orally in single doses of 80 mg fenspiride hydrochloride according to a randomised crossover pattern. Following IV administration, the plasma clearance of fenspiride was about 184 ml.min-1, and its apparent volume of distribution was moderately large (215 l). When given orally as a tablet, fenspiride exhibited fairly slow ab- sorption; the maximum plasma concentration (206 ng.ml-1) was achieved 6 h after administration. The absolute bioavailability was almost complete (90%). The tablet had slow release characteristics. The elimination half-life obtained from the plasma data was 14 to 16 h independent of the route of administration.

Intranasal administration of a therapeutic HIV vaccine (Vacc-4x induces dose-dependent systemic and mucosal immune responses in a randomized controlled trial.

Directory of Open Access Journals (Sweden)

Kristin Brekke

Full Text Available Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant.Safety and immunogenicity were tested in patients on effective ART. They were randomized to low, medium or high dose Vacc-4x or adjuvant alone, administered four times at weekly intervals with no booster. Vacc-4x-specific T cell responses were measured in vitro by proliferation and in vivo by a single DTH skin test at the end of study. Nasal and rectal mucosal secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune regulation induced by Vacc-4x was assessed by functional blockade of the regulatory cytokines IL-10 and TGF-β.Vacc-4x proliferative T cell responses increased only among the vaccinated (p ≤ 0.031. The low dose group showed the greatest increase in Vacc-4x CD8+T cell responses (p = 0.037 and developed larger DTH (p = 0.005 than the adjuvant group. Rectal (distal Vacc-4x IgA and IgG antibodies also increased (p = 0.043 in this group. In contrast, the high dose generated higher nasal (local Vacc-4x IgA (p = 0.028 and serum IgG (p = 0.030 antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x CD4+T cell responses were associated with low proliferation (r = -0.82, p < 0.001 and high regulation (r = 0.61, p = 0.010 at baseline.Intranasal administration of Vacc-4x with Endocine was safe and induced dose-dependent vaccine-specific T cell responses and both mucosal and systemic humoral responses. The clinical significance of dose, immune regulation and mucosal immunity warrants further investigation.ClinicalTrials.gov NCT01473810.

Pharmacokinetics of enrofloxacin after oral, intramuscular and bath administration in crucian carp (Carassius auratus gibelio).

Science.gov (United States)

Shan, Q; Fan, J; Wang, J; Zhu, X; Yin, Y; Zheng, G

2018-02-01

The pharmacokinetics of enrofloxacin (ENR) was studied in crucian carp (Carassius auratus gibelio) after single administration by intramuscular (IM) injection and oral gavage (PO) at a dose of 10 mg/kg body weight and by 5 mg/L bath for 5 hr at 25°C. The plasma concentrations of ENR and ciprofloxacin (CIP) were determined by HPLC. Pharmacokinetic parameters were calculated based on mean ENR or CIP concentrations using WinNonlin 6.1 software. After IM, PO and bath administration, the maximum plasma concentration (C max ) of 2.29, 3.24 and 0.36 μg/ml was obtained at 4.08, 0.68 and 0 hr, respectively; the elimination half-life (T 1/2β ) was 80.95, 62.17 and 61.15 hr, respectively; the area under the concentration-time curve (AUC) values were 223.46, 162.72 and 14.91 μg hr/ml, respectively. CIP, an active metabolite of enrofloxacin, was detected and measured after all methods of drug administration except bath. It is possible and practical to obtain therapeutic blood concentrations of enrofloxacin in the crucian carp using IM, PO and bath immersion administration. © 2017 John Wiley & Sons Ltd.

Determination of Radon-222 and Thoron Concentration in Decorative Stone Warehouses Indoor Air and the Received Effective Dose by Staff

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Amir Hossein Mahvi

2015-06-01

Full Text Available Background: Radon is a colorless, odorless, and radioactive gas that can be emitted from decorative stones such as granite, marble, etc. Inhaling radon gas in a long period may cause for incidence of lung cancer among peoples. Material and Methods: In this cross-sectional descriptive study, Radon 222 and Thoron concentrations in background and indoor air were measured in four decorative stones warehouse using portable radon meter(RTM1688-2 model. Totally, 24 samples of 24- hours concentrations in indoor air and 24 samples of 4-hours concentrations of Radon 222 and thoron in the background air at three stages were measured. Then, received effective dose of Radon 222 and Thoron was calculated by UNSCEAR equations. Results: The mean radon concentrations for indoor and background air were 74±37 and 34±16 Bq/m3, respectively. The mean radon concentrations for indoor air in decorative stones warehouses for DSW1, DSW2, DSW3 and DSW4 were 72.50±34, 98.25±43, 34.42±18 and 88.92±51 Bq/m3, respectively. The received effective dose mean of Radon 222 and Thoron by the staff at 8 working hours was 0.53±0.18 and 0.05±0.03 mSv/y and in 16 working hours was 1.05±0.36 and 0.11±0.07 mSv/y, respectively. Generally, the mean received effective dose by staff from Radon at 8 and 16 working hours was 0.58±0.2  and 1.16±0.41 mSv/y, respectively. Conclusions: Radon concentration mean in indoor air and the received effective dose mean by staff was lower than the standards level. Decorative stone warehouses were the resources for accumulation of Radon gas that can be reduced by corrective actions.

14C-Methylenebisphenylisocyanate (14C-MDI). Study of absorption after single dermal and intradermal administration in rats

International Nuclear Information System (INIS)

Leibold, E.; Hoffmann, H.D.; Hildebrand, B.

1999-01-01

The absorption, distribution and excretion of radioactivity was studied in groups of four male Wistar rats following a single dermal and intradermal administration of 14 C- Methylenebisphenylisocyanate ( 14 C-MDI) at nominal dose levels of 4.0 and 0.4 mg/cm 2 for dermal administration and 0.4 mg/animal for intradermal administration. These dose levels nominally corresponded to 40 and 4.0 mg/animal for dermal administration. Considering the animal weights, dose levels corresponded to about 140 and 14 mg/kg body weight (dermal administration) and 1.4 mg/kg body weight (intradermal administration). In the experiments with dermal administration, animals were exposed for 8 hours and sacrificed 8, 24 or 120 h after beginning of exposure. In the experiment with intradermal administration, animals were sacrificed 120 h after treatment. After dermal administration of 14 C-MDI, mean recoveries of radioactivity from all dose groups were in the range from 97.86 to 108.07% of the total radioactivity administered. Generally, the largest proportion of radioactivity was found at the application site and dressing. The total amount of radioactivity absorbed (including excreta, cage wash, tissues/organs and carcass) increased with increasing sacrifice time. Dermal absorption was very low and quantitatively similar at both dose levels; maximally ca. 0.9 % of the applied radioactivity was absorbed. After intradermal administration of 14 C-MDI, the mean recovery of radioactivity was 100.90 % of the radioactivity administered. The largest proportion of radioactivity was found at the application site. The total amount of radioactivity absorbed (including excreta, cage wash, tissues/organs and carcass) amounted to about 26 % of the radioactivity applied. Irrespective of the mode of administration of 1 4C -MDI, concentrations of radioactivity in tissues and organs generally were below 1 μg Eq/g at 120 h after administration. In summary, the results of this study comparing systemic

Relative effects of plasma, fibrinogen concentrate, and factor XIII on ROTEM coagulation profiles in an in vitro model of massive transfusion in trauma.

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Schmidt, David E; Halmin, Märit; Wikman, Agneta; Östlund, Anders; Ågren, Anna

2017-10-01

Massive traumatic haemorrhage is aggravated through the development of trauma-induced coagulopathy, which is managed by plasma transfusion and/or fibrinogen concentrate administration. It is yet unclear whether these treatments are equally potent in ensuring adequate haemostasis, and whether additional factor XIII (FXIII) administration provides further benefits. In this study, we compared ROTEM whole blood coagulation profiles after experimental massive transfusion with different transfusion regimens in an in vitro model of dilution- and transfusion-related coagulopathy. Healthy donor blood was mixed 1 + 1 with six different transfusion regimens. Each regimen contained RBC, platelet concentrate, and either fresh frozen plasma (FFP) or Ringer's acetate (RA). The regimens were further augmented through addition of a low- or medium-dose fibrinogen concentrate and FXIII. Transfusion with FFP alone was insufficient to maintain tissue-factor activated clot strength, coincidental with a deficiency in fibrin-based clot strength. Fibrinogen concentrate conserved, but did not improve coagulation kinetics and overall clot strength. Only combination therapy with FFP and low-dose fibrinogen concentrate improved both coagulation kinetics and fibrin-based clot strength. Administration of FXIII did not result in an improvement of clot strength. In conclusion, combination therapy with both FFP and low-dose fibrinogen concentrate improved clotting time and produced firm clots, representing a possible preferred first-line regimen to manage trauma-induced coagulopathy when RBC and platelets are also transfused. Further research is required to identify optimal first-line transfusion fluids for massive traumatic haemorrhage.

Nanostructured lipid carriers-based flurbiprofen gel after topical administration: acute skin irritation, pharmacodynamics, and percutaneous absorption mechanism.

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Song, Aihua; Su, Zhen; Li, Sanming; Han, Fei

2015-01-01

In order to assess the preliminary safety and effectiveness of nanostructured lipid carriers-based flurbiprofen gel (FP NLC-gel), the acute irritation test, in vivo pharmacodynamics evaluation and pharmacokinetic study were investigated after topical application. No dropsy and erythema were observed after continuous dosing 7 d of FP NLC-gel on the rabbit skin, and the xylene-induced ear drossy could be inhibited by FP NLC-gel at different dosages. The maximum concentration of FP in rats muscle was 2.03 μg/g and 1.55 μg/g after oral and topical administration, respectively. While the peak concentration in untreated muscle after topical administration was only 0.37 μg/mL. And at any time, following topical administration the mean muscle-plasma concentration ratio Cmuscle/CPlasma was obviously higher than that following oral administration. Results indicated that FP could directly penetrate into the subcutaneous muscle tissue from the administration site. Thus, the developed FP NLC-gel could be a safe and effective vehicle for topical delivery of FP.

Radon concentration in air and external gamma dose rate. Is there a correlation?

International Nuclear Information System (INIS)

Yoshimura, E.M.; Umisedo, N.K.; Marcos Rizzotto; Hugo Velasco; Valladares, D.L.

2016-01-01

We checked the existence of correlations between experimentally determined radon concentration in indoor air and gamma dose rate, in different environments: residences, workplaces in subway stations and radiotherapies, and a gold mine. Except for the mine environment, where a linear correlation (r 2 = 0.86) was obtained with statistical significance, we found no correlations between those quantities. Both radiation sources are originated from natural radionuclides, nonetheless the observation of correlations depends on various conditions, as we discuss here. (author)

Concentration of metallothionein in mice livers after a small dose of irradiation

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Saitou, Mikio; Yanai, Takanori; Hasegawa, Hidenao; Otsu, Hiroshi; Sato, Fumiaki [Inst. for Environmental Sciences, Rokkasho, Aomori (Japan); Akata, Naofumi; Kanaiwa-Kudo, Shouko; Matsumoto, Tsuneya; Noda, Yuko

1998-12-01

This study was made to determine whether metallothionein (MT) is induced by a small dose (0.5 Gy) irradiation. One hundred B6C3F1/Nrs mice of each sex, 8-10 weeks old, were used in the sham study (unirradiated controls) and experimental (irradiated) groups. Eighty mice of each sex were given acute whole body irradiation with {sup 197}Cs{gamma}-rays under SPF conditions; two doses of 0.5 and 5.0 Gy at 30 cm distance from the source at the rate of 0.563 Gy/min. Twenty mice of each sex were used in the sham study. Every ten male and female mouse was killed by cervical dislocation on days 1, 7, 14 and 21 after irradiation. The same numbers of male and female control mice were killed on days 0 and 21. Livers were removed immediately after death, and concentration of MT was examined. In both the males and females, the MT concentration of the 5 Gy-group peaked on the first day after irradiation, and there was no difference in comparison with the control values between the 7th and 21st days. In contrast, on no day did the MT concentration for the 0.5 Gy-group showed a significant difference from the control group. The time dependency patterns of the female and male mice also showed no significant differences for 5 Gy- and 0.5 Gy-groups, but the mean values of the MT concentration was lower in the males than in the females on the 1st day. Results of the direct quantitation of MT by the enzyme-linked immunoabsorbent assay (ELISA) also showed peak MT accumulation on the 1st day for both male and female mice. These were also shown by the atomic absorption spectrometry (AAS) and the inductively coupled plasma mass spectrometry (ICP-MS) analyses. But peak heights for the males and females showed a tendency inverse to that of the AAS and ICP-MS analyses. This discrepancy is attributable to the technical problem encountered in the experiment. On the basis of our findings, MT does not seem to be related to acquired radioresistance in mice. (K.H.)

Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

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Zygmunt Warzecha

2017-04-01

Full Text Available Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Results: Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Conclusion: Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.

A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration

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Sun CL

2015-05-01

Full Text Available Changling Sun,1,3,* Xueling Wang,1,* Zhaozhu Zheng,2 Dongye Chen,1 Xiaoqin Wang,2 Fuxin Shi,1 Dehong Yu,1 Hao Wu11Department of Otolaryngology–Head and Neck Surgery, Xinhua Hospital, Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, 2National Engineering Laboratory for Modern Silk, Soochow University, Suzhou, 3Department of Otolaryngology–Head and Neck Surgery, Affiliated Hospital of Jiangnan University, The Fourth People’s Hospital of Wuxi City, Wuxi, People’s Republic of China*These authors have contributed equally to this workAbstract: This study aimed to investigate the sustained drug release properties and hearing protection effect of polyethylene glycol-coated polylactic acid (PEG-PLA stealth nanoparticles loaded with dexamethasone (DEX. DEX was fabricated into PEG-PLA nanoparticles using an emulsion and evaporation technique, as previously reported. The DEX-loaded PEG-PLA nanoparticles (DEX-NPs had a hydrodynamic diameter of 130±4.78 nm, and a zeta potential of -26.13±3.28 mV. The in vitro release of DEX from DEX-NPs lasted 24 days in phosphate buffered saline (pH 7.4, 5 days in artificial perilymph (pH 7.4, and 1 day in rat plasma. Coumarin 6-labeled NPs placed onto the round window membrane (RWM of guinea pigs penetrated RWM quickly and accumulated to the organs of Corti, stria vascularis, and spiral ganglion cells after 1 hour of administration. The DEX-NPs locally applied onto the RWM of guinea pigs by a single-dose administration continuously released DEX in 48 hours, which was significantly longer than the free DEX that was cleared out within 12 hours after administration at the same dose. Further functional studies showed that locally administrated single-dose DEX-NPs effectively preserved outer hair cells in guinea pigs after cisplatin insult and thus significantly attenuated hearing loss at 4 kHz and 8�

Maternal methadone dosing schedule and fetal neurobehavior

Science.gov (United States)

Jansson, Lauren M.; DiPietro, Janet A.; Velez, Martha; Elko, Andrea; Knauer, Heather; Kivlighan, Katie T.

2008-01-01

Objective Daily methadone maintenance is the standard of care for opiate dependency during pregnancy. Previous research has indicated that single-dose maternal methadone administration significantly suppresses fetal neurobehaviors. The purpose of this study was to determine if split-dosing would have less impact on fetal neurobehavior than single-dose administration. Methods Forty methadone-maintained women were evaluated at peak and trough maternal methadone levels on single- and split-dosing schedules. Monitoring sessions occurred at 36 and 37 weeks gestation in a counterbalanced study design. Fetal measures included heart rate, variability, accelerations, motor activity and fetal movement-heart rate coupling (FM-FHR). Maternal measures included heart period, variability, skin conductance, respiration and vagal tone. Repeated measure analysis of variance was used to evaluate within-subject changes between split- and single-dosing regimens. Results All fetal neurobehavioral parameters were suppressed by maternal methadone administration, regardless of dosing regimen. Fetal parameters at peak were significantly lower during single vs. split methadone administration. FM-FHR coupling was less suppressed from trough to peak during split-dosing vs. single-dosing. Maternal physiologic parameters were generally unaffected by dosing condition. Conclusion Split- dosed fetuses displayed less neurobehavioral suppression from trough to peak maternal methadone levels as compared to single-dosed fetuses. Split-dosing may be beneficial for methadone-maintained pregnant women. PMID:19085624

Administration of the non-steroidal anti-inflammatory drug ibuprofen increases macrophage concentrations but reduces necrosis during modified muscle use

Science.gov (United States)

Cheung, E. V.; Tidball, J. G.

2003-01-01

OBJECTIVE: To test the hypothesis that ibuprofen administration during modified muscle use reduces muscle necrosis and invasion by select myeloid cell populations. METHODS: Rats were subjected to hindlimb unloading for 10 days, after which they experienced muscle reloading by normal weight-bearing to induce muscle inflammation and necrosis. Some animals received ibuprofen by intraperitoneal injection 8 h prior to the onset of muscle reloading, and then again at 8 and 16 h following the onset of reloading. Other animals received buffer injection at 8 h prior to reloading and then ibuprofen at 8 and 16 h following the onset of reloading. Control animals received buffer only at each time point. Quantitative immunohistochemical analysis was used to assess the presence of necrotic muscle fibers, total inflammatory infiltrate, neutrophils, ED1+ macrophages and ED2+ macrophages at 24 h following the onset of reloading. RESULT: Administration of ibuprofen beginning 8 h prior to reloading caused significant reduction in the concentration of necrotic fibers, but increased the concentration of inflammatory cells in muscle. The increase in inflammatory cells was attributable to a 2.6-fold increase in the concentration of ED2+ macrophages. Animals treated with ibuprofen 8 h following the onset of reloading showed no decrease in muscle necrosis or increase in ED2+ macrophage concentrations. CONCLUSION: Administration of ibuprofen prior to increased muscle loading reduces muscle damage, but increases the concentration of macrophages that express the ED2 antigen. The increase in ED2+ macrophage concentration and decrease in necrosis may be mechanistically related because ED2+ macrophages have been associated with muscle regeneration and repair.

Optimizing lithium dosing in hemodialysis

DEFF Research Database (Denmark)

Bjarnason, N H; Munkner, R; Kampmann, J P

2006-01-01

in which we developed an algorithm based on a 2-compartment distribution without elimination. The GFR estimate led to plasma concentrations 3-4 times lower than those anticipated. In contrast, the estimates based on V(d) and the algorithm derived from pharmacokinetic modeling led to comparable loading dose...... in this patient with no residual kidney function. We did not observe adverse effects related to this regimen, which was monitored from 18 days to 8 months of therapy, and the patient experienced relief from her severe depressive disorder. In conclusion, dialysis patients may be treated with lithium administrated...

Changes in heparin dose response slope during cardiac surgery: possible result in inaccuracy in predicting heparin bolus dose requirement to achieve target ACT.

Science.gov (United States)

Ichikawa, Junko; Mori, Tetsu; Kodaka, Mitsuharu; Nishiyama, Keiko; Ozaki, Makoto; Komori, Makiko

2017-09-01

The substantial interpatient variability in heparin requirement has led to the use of a heparin dose response (HDR) technique. The accuracy of Hepcon-based heparin administration in achieving a target activated clotting time (ACT) using an HDR slope remains controversial. We prospectively studied 86 adult patients scheduled for cardiac surgery requiring cardiopulmonary bypass. The total dose of calculated heparin required for patient and pump priming was administered simultaneously to achieve a target ACT of 450 s for HDR on the Hepcon HMS system. Blood samples were obtained after the induction of anesthesia, at 3 min after heparin administration and after the initiation of CPB to measure kaolin ACT, HDR slope, whole-blood heparin concentration based on the HDR slope and anti-Xa heparin concentration, antithrombin and complete blood count. The target ACT of 450 s was not achieved in 68.6% of patients. Compared with patients who achieved the target ACT, those who failed to achieve their target ACT had a significantly higher platelet count at baseline. Correlation between the HDR slope and heparin sensitivity was poor. Projected heparin concentration and anti-Xa heparin concentration are not interchangeable based on the Bland-Altman analysis. It can be hypothesized that the wide discrepancy in HDR slope versus heparin sensitivity may be explained by an inaccurate prediction of the plasma heparin level and/or the change in HDR of individual patients, depending on in vivo factors such as extravascular sequestration of heparin, decreased intrinsic antithrombin activity level and platelet count and/or activity.

Effect of Low Dose Gamma Radiation Upon the Concentration of Calcium and Inorganic Phosphorus in the Blood Plasma of Chickens

International Nuclear Information System (INIS)

Kraljevic, P.; Vilic, M.; Miljanic, S.; Simpraga, M.

2003-01-01

In our previous paper it has been showed that the irradiation of chickens eggs before incubation by low dose gamma irradiation effects upon growth of the chickens hatched from irradiated eggs as well as upon activity of ALT and AST, and on the concentration of total proteins, glucose and cholesterol in the blood plasma of those chickens. Therefore in this paper an attempt was made to determine the effects of irradiation of eggs by low dose of ionizing radiation on the 19th day of incubation upon the concentration of calcium (Ca) and inorganic phosphorus (P) in the blood plasma of chickens hatched from irradiated eggs. The eggs of heavy breeding chickens (Gent, line COBB 500) were irradiated by a dose of 0.15 Gy gamma radiation (6 0C o source) on the 19th day of incubation. Along with the chickens, which were hatched from irradiated eggs, there was a control group of chickens hatched from nonirradiated eggs. All other conditions were the same for both groups. After hatching, blood samples were taken on day 1, 3, 5, 7, 10, 20, 30 and 42. The concentration of Ca was determined calorimetrically using Randox optimized kits, while the concentration of P was determined by Herbos dijagnostika Sisak (Croatia) optimized kits. The concentration of Ca in the blood plasma of chickens hatched from irradiated eggs was significantly increased on the first day, while it was decreased on the day 42. The concentration of P was decreased on the first day in blood plasma of chickens hatched from irradiated eggs. The fact that the concentration of both minerals in blood plasma of chickens hatched from irradiated eggs was significantly changed on the first day proves that the irradiation of eggs by low dose of ionizing radiation on the nineteenth day of incubation had an effect on metabolism of both minerals in those chickens. (author)

Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration.

Science.gov (United States)

McFadden, Lisa M; Hoonakker, Amanda J; Vieira-Brock, Paula L; Stout, Kristen A; Sawada, Nicole M; Ellis, Jonathan D; Allen, Scott C; Walters, Elliot T; Nielsen, Shannon M; Gibb, James W; Alburges, Mario E; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

2011-08-01

Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent [i.e., postnatal day (PND) 40] rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a "challenge" high-dose METH regimen when administered at PND90. Mechanisms underlying this "resistance" were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity. Copyright © 2011 Wiley-Liss, Inc.

Evaluation of divided attention psychophysical task performance and effects on pupil sizes following smoked, vaporized and oral cannabis administration.

Science.gov (United States)

Newmeyer, Matthew N; Swortwood, Madeleine J; Taylor, Megan E; Abulseoud, Osama A; Woodward, Thomas H; Huestis, Marilyn A

2017-08-01

Establishing science-based driving per se blood Δ 9 -tetrahydrocannabinol (THC) limits is challenging, in part because of prolonged THC detection in chronic, frequent users. Therefore, documenting observable signs of impairment is important for driving under the influence of drugs. We evaluated frequent and occasional cannabis smokers' performance on the modified Romberg balance, one leg stand (OLS), and walk and turn (WAT) tasks, and pupil size effects following controlled placebo (0.001% THC), smoked, vaporized and oral (6.9% [~50.4 mg] THC) cannabis administration. Significant effects following inhaled doses were not observed due to delayed tasks administration 1.5 and 3.5 h post-dose, but significant impairment was observed after oral dosing (blood THC concentrations peaked 1.5-3.5 h post-dose). Occasional smokers' odds of exhibiting ≥2 clues on the OLS or WAT following oral dosing were 6.4 (95% CI 2.3-18.4) times higher than after placebo, with THC and 11-hydroxy-THC blood concentrations individually producing odds ratios of 1.3 (1.1-1.5) and 1.5 (1.3-1.8) for impairment in these tasks, respectively. Pupil sizes after oral dosing under the direct lighting condition were significantly larger than after placebo by mean (SE, 95% CI) 0.4 (0.1, 0.2-0.6) mm at 1.5 h and 0.5 (0.2, 0.2-0.8) mm at 3.5 h among all participants. Oral cannabis administration impaired occasional cannabis users' performance on the OLS and WAT tasks compared to placebo, supporting other reports showing these tasks are sensitive to cannabis-related impairment. Occasional smokers' impairment was related to blood THC and 11-hydroxy-THC concentrations. These are important public health policy findings as consumption of edible cannabis products increases. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Tacrolimus concentration/dose ratio as a therapeutic drug monitoring strategy: The influence of gender and comedication

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Rančić Nemanja

2015-01-01

Full Text Available Background/Aim. A combination of tacrolimus and other drugs such as corticosteroids has been commonly used immunosuppresive regimens. On the other hand, there is a growing body of evidence that male and female may differ in their response to the equal drug treatment. The aim of the study was to estimated the use of tacrolimus concentration/dose (C/D ratio for the assessment of the influence of gender differences and comedication on tacrolimus exposure in renal transplant recipients. Methods. This prospective case series study included 54 patients, in which the unit of monitoring was outpatient examination (1,872 of the renal transplant patients. The patients were monitored in the period 2010-2014, starting one month after the transplantation. Tacrolimus trough concentrations (TTC were measured by chemiluminescence microparticles immunoassay. Results. TTC and the tacrolimus C/D ratio were significantly lower in the females comparing with the males. Contrary to the males, in the females a significant increase of the tacrolimus daily dose (TDD per body weight and TTC, along with the corticosteroid dose increase, was not accompanied by any significant changes in the tacrolimus C/D ratio; in different corticosteroid doses faster elimination of tacrolimus was found with the exception of the doses > 0.25 mg/kg. In the patients treated with proton pump inhibitors, mainly with pantoprazole TDD per body weight and TTC were significantly higher, while the tacrolimus C/D ratio was significantly lower compared to the patients without this treatment. In the patients treated with calcium channel blockers, TDD per body weight was significantly lower (particularly with amlodipine while the tacrolimus C/D ratio was higher compared to the patients who were not treated by them. Conclusion. A lower tacrolimus exposure was detected in females in comparison to males. When gender differences were considered in the context of different corticosteroid doses, faster

Plasma concentrations, behavioural and physiological effects following intravenous and intramuscular detomidine in horses.

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Mama, K R; Grimsrud, K; Snell, T; Stanley, S

2009-11-01

Detomidine hydrochloride is used to provide sedation, muscle relaxation and analgesia in horses, but a lack of information pertaining to plasma concentration has limited the ability to correlate drug concentration with effect. To build on previous information and assess detomidine for i.v. and i.m. use in horses by simultaneously assessing plasma drug concentrations, physiological parameters and behavioural characteristics. Systemic effects would be seen following i.m. and i.v. detomidine administration and these effects would be positively correlated with plasma drug concentrations. Behavioural (e.g. head position) and physiological (e.g. heart rate) responses were recorded at fixed time points from 4 min to 24 h after i.m. or i.v. detomidine (30 microg/kg bwt) administration to 8 horses. Route of administration was assigned using a balanced crossover design. Blood was sampled at predetermined time points from 0.5 min to 48 h post administration for subsequent detomidine concentration measurements using liquid chromatography-mass spectrometry. Data were summarised as mean +/- s.d. for subsequent analysis of variance for repeated measures. Plasma detomidine concentration peaked earlier (1.5 min vs. 1.5 h) and was significantly higher (105.4 +/- 71.6 ng/ml vs. 6.9 +/- 1.4 ng/ml) after i.v. vs. i.m. administration. Physiological and behavioural changes were of a greater magnitude and observed at earlier time points for i.v. vs. i.m. groups. For example, head position decreased from an average of 116 cm in both groups to a low value 35 +/- 23 cm from the ground 10 min following i.v. detomidine and to 64 +/- 24 cm 60 min after i.m. detomidine. Changes in heart rate followed a similar pattern; low value of 17 beats/min 10 min after i.v. administration and 29 beats/min 30 min after i.m. administration. Plasma drug concentration and measured effects were correlated positively and varied with route of administration following a single dose of detomidine. Results support a

Impact of intra-arterial administration of boron compounds on dose-volume histograms in boron neutron capture therapy for recurrent head-and-neck tumors

International Nuclear Information System (INIS)

Suzuki, Minoru; Sakurai, Yoshinori; Nagata, Kenji; Kinashi, Yuko; Masunaga, Shinichiro; Ono, Koji; Maruhashi, Akira; Kato, Ituro; Fuwa, Nobukazu; Hiratsuka, Junichi; Imahori, Yoshio

2006-01-01

Purpose: To analyze the dose-volume histogram (DVH) of head-and-neck tumors treated with boron neutron capture therapy (BNCT) and to determine the advantage of the intra-arterial (IA) route over the intravenous (IV) route as a drug delivery system for BNCT. Methods and Materials: Fifteen BNCTs for 12 patients with recurrent head-and-neck tumors were included in the present study. Eight irradiations were done after IV administration of boronophenylalanine and seven after IA administration. The maximal, mean, and minimal doses given to the gross tumor volume were assessed using a BNCT planning system. Results: The results are reported as median values with the interquartile range. In the IA group, the maximal, mean, and minimal dose given to the gross tumor volume was 68.7 Gy-Eq (range, 38.8-79.9), 45.0 Gy-Eq (range, 25.1-51.0), and 13.8 Gy-Eq (range, 4.8-25.3), respectively. In the IV group, the maximal, mean, and minimal dose given to the gross tumor volume was 24.2 Gy-Eq (range, 21.5-29.9), 16.4 Gy-Eq (range, 14.5-20.2), and 7.8 Gy-Eq (range, 6.8-9.5), respectively. Within 1-3 months after BNCT, the responses were assessed. Of the 6 patients in the IV group, 2 had a partial response, 3 no change, and 1 had progressive disease. Of 4 patients in the IA group, 1 achieved a complete response and 3 a partial response. Conclusion: Intra-arterial administration of boronophenylalanine is a promising drug delivery system for head-and-neck BNCT

An in situ caries study on the interplay between fluoride dose and concentration in milk.

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Lippert, F; Martinez-Mier, E A; Zero, D T

2014-07-01

This randomized, cross-over in situ study investigated the impact of sodium fluoride dose and concentration in milk on caries lesion rehardening, fluoridation and acid resistance. Twenty-eight subjects wore two gauze-covered enamel specimens with preformed lesions placed buccally on their mandibular partial dentures for three weeks. Participants used fluoride-free dentifrice throughout the study and consumed once daily one of the five study treatments: no fluoride in 200 ml milk (0F-200), 1.5 or 3 mg fluoride in either 100 (1.5F-100; 3F-100) or 200 ml milk (1.5F-200; 3F-200). After three weeks, specimens were retrieved. Knoop hardness was used to determine rehardening and resistance to a secondary acid challenge. Enamel fluoride uptake (EFU) was determined using a microbiopsy technique. A linear fluoride dose-response was observed for all study variables which exhibited similar overall patterns. All the treatments resulted in rehardening, with 0F-200 inducing the least and 3F-100 the most. Apart from 1.5F-200, all the treatments resulted in statistically significantly more rehardening compared to 0F-200. The fluoride doses delivered in 100 ml provided directionally although not statistically significantly more rehardening than those delivered in 200 ml milk. EFU data exhibited better differentiation between treatments: all fluoridated milk treatments delivered more fluoride to lesions than 0F-200; fluoride in 100 ml demonstrated statistically significantly higher EFU than fluoride in 200 ml milk. Findings for acid resistance were also more discerning than rehardening data. The present study has provided further evidence for the anti-caries benefits of fluoridated milk. Both fluoride dose and concentration appear to impact the cariostatic properties of fluoride in milk. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tissue distribution of enrofloxacin after intramammary or simulated systemic administration in isolated perfused sheep udders.

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López Cadenas, Cristina; Fernández Martínez, Nélida; Sierra Vega, Matilde; Diez Liébana, Maria J; Gonzalo Orden, Jose M; Sahagún Prieto, Ana M; García Vieitez, Juan J

2012-11-01

To determine the tissue distribution of enrofloxacin after intramammary or simulated systemic administration in isolated perfused sheep udders by measuring its concentration at various sample collection sites. 26 udders (obtained following euthanasia) from 26 healthy lactating sheep. For each isolated udder, 1 mammary gland was perfused with warmed, gassed Tyrode solution. Enrofloxacin (1 g of enrofloxacin/5 g of ointment) was administered into the perfused gland via the intramammary route or systemically via the perfusion fluid (equivalent to a dose of 5 mg/kg). Samples of the perfusate were obtained every 30 minutes for 180 minutes; glandular tissue samples were obtained at 2, 4, 6, and 8 cm from the teat base after 180 minutes. The enrofloxacin content of the perfusate and tissue samples was analyzed via high-performance liquid chromatography with UV detection. After intramammary administration, maximun perfusate enrofloxacin concentration was detected at 180 minutes and, at this time, mean tissue enrofloxacin concentration was detected and mean tissue enrofloxacin concentration was 123.80, 54.48, 36.72, and 26.42 μg/g of tissue at 2, 4, 6, and 8 cm from the teat base, respectively. Following systemic administration, perfusate enrofloxacin concentration decreased with time and, at 180 minutes, tissue enrofloxacin concentrations ranged from 40.38 to 35.58 μg/g of tissue. By 180 minutes after administration via the intramammary or systemic route in isolated perfused sheep mammary glands, mean tissue concentration of enrofloxacin was greater than the minimum inhibitory concentration required to inhibit growth of 90% of many common mastitis pathogens in sheep. Use of either route of administration (or in combination) appears suitable for the treatment of acute mastitis in sheep.

Comparative chlorpyrifos pharmacokinetics via multiple routes of exposure and vehicles of administration in the adult rat

International Nuclear Information System (INIS)

Smith, Jordan Ned; Campbell, James A.; Busby-Hjerpe, Andrea L.; Lee, Sookwang; Poet, Torka S.; Barr, Dana B.; Timchalk, Charles

2009-01-01

Chlorpyrifos (CPF) is a commonly used organophosphorus pesticide. A number of toxicity and mechanistic studies have been conducted in animals, where CPF has been administered via a variety of different exposure routes and dosing vehicles. This study compared chlorpyrifos (CPF) pharmacokinetics using oral, intravenous (IV), and subcutaneous (SC) exposure routes and corn oil, saline/Tween 20, and dimethyl sulfoxide (DMSO) as dosing vehicles. Two groups of rats were co-administered target doses (5 mg/kg) of CPF and isotopically labeled CPF (L-CPF). One group was exposed by both oral (CPF) and IV (L-CPF) routes using saline/Tween 20 vehicle; whereas, the second group was exposed by the SC route using two vehicles, corn oil (CPF) and DMSO (L-CPF). A third group was only administered CPF by the oral route in corn oil. For all treatments, blood and urine time course samples were collected and analyzed for 3,5,6-trichloro-2-pyridinol (TCPy), and isotopically labeled 3,5,6-trichloro-2-pyridinol (L-TCPy). Peak TCPy/L-TCPy concentrations in blood (20.2 μmol/l), TCPy/L-TCPy blood AUC (94.9 μmol/l h), and percent of dose excreted in urine (100%) were all highest in rats dosed orally with CPF in saline/Tween 20 and second highest in rats dosed orally with CPF in corn oil. Peak TCPy concentrations in blood were more rapidly obtained after oral administration of CPF in saline/Tween 20 compared to all other dosing scenarios (>1.5 h). These results indicate that orally administered CPF is more extensively metabolized than systemic exposures of CPF (SC and IV), and vehicle of administration also has an effect on absorption rates. Thus, equivalent doses via different routes and/or vehicles of administration could potentially lead to different body burdens of CPF, different rates of bioactivation to CPF-oxon, and different toxic responses. Simulations using a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for CPF are consistent with these possibilities

Effect of chronic administration of phenobarbital, or bromide, on pharmacokinetics of levetiracetam in dogs with epilepsy.

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Muñana, K R; Nettifee-Osborne, J A; Papich, M G

2015-01-01

Levetiracetam (LEV) is a common add-on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs. To evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs. Eighteen client-owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB-BR group, n = 6). Prospective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high-pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area-under-the-curve (AUC) calculated to the last measured time point. Compared to the PB and PB-BR groups, the BR group had significantly higher peak concentration (Cmax ) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 μg/mL, respectively, P phenobarbital in dogs. Copyright © 2015 by the American College of Veterinary Internal Medicine.

[Estimation of effective doses derived from radon in selected SPA centers that use geothermal waters based on the information of radon concentrations].

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Walczak, Katarzyna; Zmyślony, Marek

2013-01-01

Geothermal waters contain, among other components, soluble radon gas. Alpha radioactive radon is a health hazard to humans, especially when it gets into the respiratory tract. SPA facilities that use geothermal water can be a source of an increased radiation dose to people who stay there. Based on the available literature concerning radon concentrations, we assessed exposure to radon among people - workers and visitors of Spa centers that use geothermal waters. Radon concentrations were analyzed in 17 geothermal centers: in Greece (3 centers), Iran (5), China (4) and India (5). Doses recived by people in the SPA were estimated using the formula that 1 hour exposure to 1 Bq/m3 of radon concentration and equilibrium factor F = 0.4 corresponds to an effective dose of 3.2 nSv. We have found that radon levels in SPAs are from a few to several times higher than those in confined spaces, where geothermal waters are not used (e.g., residential buildings). In 82% of the analyzed SPAs, workers may receive doses above 1 mSv/year. According to the relevant Polish regulations, people receiving doses higher than 1 mSv/year are included in category B of radiation exposure and require regular dosimetric monitoring. Doses received by SPA visitors are much lower because the time of their exposure to radon released from geothermal water is rather short. The analysis of radon concentration in SPA facilities shows that the radiological protection of people working with geothermal waters plays an important role. It seems reasonable to include SPA workers staying close to geotermal waters into a dosimetric monitoring program.

Dose-dependent effects of endotoxin on neurobehavioral functions in humans.

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Jan-Sebastian Grigoleit

Full Text Available Clinical and experimental evidence document that inflammation and increased peripheral cytokine levels are associated with depression-like symptoms and neuropsychological disturbances in humans. However, it remains unclear whether and to what extent cognitive functions like memory and attention are affected by and related to the dose of the inflammatory stimulus. Thus, in a cross-over, double-blind, experimental approach, healthy male volunteers were administered with either placebo or bacterial lipopolysaccharide (LPS at doses of 0.4 (n = 18 or 0.8 ng/kg of body weight (n = 16. Pro- and anti-inflammatory cytokines, norephinephrine and cortisol concentrations were analyzed before and 1, 1.75, 3, 4, 6, and 24 h after injection. In addition, changes in mood and anxiety levels were determined together with working memory (n-back task and long term memory performance (recall of emotional and neutral pictures of the International Affective Picture System. Endotoxin administration caused a profound transient physiological response with dose-related elevations in body temperature and heart rate, increases in plasma interleukin (IL-6, IL-10, tumor necrosis factor (TNF-α and IL-1 receptor antagonist (IL-1ra, salivary and plasma cortisol, and plasma norepinephrine. These changes were accompanied by dose-related decreased mood and increased anxiety levels. LPS administration did not affect accuracy in working memory performance but improved reaction time in the high-dose LPS condition compared to the control conditon. In contrast, long-term memory performance was impaired selectively for emotional stimuli after administration of the lower but not of the higher dose of LPS. These data suggest the existence of at least two counter-acting mechanisms, one promoting and one inhibiting cognitive performance during acute systemic inflammation.

Multifaceted empathy of healthy volunteers after single doses of MDMA: A pooled sample of placebo-controlled studies.

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Kuypers, Kim Pc; Dolder, Patrick C; Ramaekers, Johannes G; Liechti, Matthias E

2017-05-01

Previous placebo-controlled experimental studies have shown that a single dose of MDMA can increase emotional empathy in the multifaceted empathy test (MET) without affecting cognitive empathy. Although sufficiently powered to detect main effects of MDMA, these studies were generally underpowered to also validly assess contributions of additional parameters, such as sex, drug use history, trait empathy and MDMA or oxytocin plasma concentrations. The present study examined the robustness of the MDMA effect on empathy and investigated the moderating role of these additional parameters. Participants ( n = 118) from six placebo-controlled within-subject studies and two laboratories were included in the present pooled analysis. Empathy (MET), MDMA and oxytocin plasma concentrations were assessed after oral administration of MDMA (single dose, 75 or 125 mg). Trait empathy was assessed using the interpersonal reactivity index. We confirmed that MDMA increased emotional empathy at both doses without affecting cognitive empathy. This MDMA-related increase in empathy was most pronounced during presentation of positive emotions as compared with negative emotions. MDMA-induced empathy enhancement was positively related to MDMA blood concentrations measured before the test, but independent of sex, drug use history and trait empathy. Oxytocin concentrations increased after MDMA administration but were not associated with behavioral effects. The MDMA effects on emotional empathy were stable across laboratories and doses. Sex did not play a moderating role in this effect, and oxytocin levels, trait empathy and drug use history were also unrelated. Acute drug exposure was of significant relevance in the MDMA-induced emotional empathy elevation.

Impact of carprofen administration on stress and nociception responses of calves to cautery dehorning.

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Stock, M L; Barth, L A; Van Engen, N K; Millman, S T; Gehring, R; Wang, C; Voris, E A; Wulf, L W; Labeur, Léa; Hsu, W H; Coetzee, J F

2016-02-01

The objective of this study was to investigate the effects of carprofen administered immediately before cautery dehorning on nociception and stress. Forty Holstein calves aged approximately 6 to 8 wk old were either placebo treated and sham dehorned ( = 10) or cautery dehorned following administration of carprofen (1.4 mg/kg) subcutaneously ( = 10) or orally ( = 10) or a subcutaneous and oral placebo ( = 10) in a randomized, controlled trial. All animals were given a cornual nerve block using lidocaine before dehorning. Response variables including mechanical nociception threshold, ocular temperature, heart rate, and respiratory rate were measured before and following cautery dehorning for 96 h. Blood samples were also collected over 96 h following dehorning and analyzed for plasma cortisol and substance P concentrations by RIA. Plasma carprofen concentration and ex vivo PGE concentrations were also determined for this time period. Average daily gain was calculated for 7 d after dehorning. Data were analyzed using a linear mixed effects model with repeated measures, controlling for baseline values by their inclusion as a covariate in addition to planned contrasts. Dehorning was associated with decreased nociception thresholds throughout the study and a stress response immediately after dehorning, following the loss of local anesthesia, and 48 h after dehorning compared with sham-dehorned calves. Carprofen was well absorbed after administration and reached concentrations that inhibited ex vivo PGE concentrations for 72 h (subcutaneous) and 96 h (oral) compared with placebo-treated calves ( Carprofen-treated calves tended to be less sensitive ( = 0.097) to nociceptive threshold tests. Overall, at the dosing regimen studied, the effect of carprofen on sensitivity and stress following cautery dehorning was minimal. Consideration of route of administration and dose determination studies may be warranted.

The Safety, Effectiveness and Concentrations of Adjusted Lopinavir/Ritonavir in HIV-Infected Adults on Rifampicin-Based Antitubercular Therapy

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Decloedt, Eric H.; Maartens, Gary; Smith, Peter; Merry, Concepta; Bango, Funeka; McIlleron, Helen

2012-01-01

Objective Rifampicin co-administration dramatically reduces plasma lopinavir concentrations. Studies in healthy volunteers and HIV-infected patients showed that doubling the dose of lopinavir/ritonavir (LPV/r) or adding additional ritonavir offsets this interaction. However, high rates of hepatotoxicity were observed in healthy volunteers. We evaluated the safety, effectiveness and pre-dose concentrations of adjusted doses of LPV/r in HIV infected adults treated with rifampicin-based tuberculosis treatment. Methods Adult patients on a LPV/r-based antiretroviral regimen and rifampicin-based tuberculosis therapy were enrolled. Doubled doses of LPV/r or an additional 300 mg of ritonavir were used to overcome the inducing effect of rifampicin. Steady-state lopinavir pre-dose concentrations were evaluated every second month. Results 18 patients were enrolled with a total of 79 patient months of observation. 11/18 patients were followed up until tuberculosis treatment completion. During tuberculosis treatment, the median (IQR) pre-dose lopinavir concentration was 6.8 (1.1–9.2) mg/L and 36/47 (77%) were above the recommended trough concentration of 1 mg/L. Treatment was generally well tolerated with no grade 3 or 4 toxicity: 8 patients developed grade 1 or 2 transaminase elevation, 1 patient defaulted additional ritonavir due to nausea and 1 patient developed diarrhea requiring dose reduction. Viral loads after tuberculosis treatment were available for 11 patients and 10 were undetectable. Conclusion Once established on treatment, adjusted doses of LPV/r co-administered with rifampicin-based tuberculosis treatment were tolerated and LPV pre-dose concentrations were adequate. PMID:22412856

Administrative limits for tritium concentrations found in non-potable groundwater at nuclear power facilities

International Nuclear Information System (INIS)

Parker, R.; Hart, D.; WIllert, C.

2012-01-01

Currently, there is a regulatory limit available for tritium in drinking water, but no such limit for non-potable groundwater. Voluntary administrative limits for site groundwater may be established at nuclear power facilities to ensure minimal risk to human health and the environment, and provide guidance for investigation or other actions intended to prevent exceedances of future regulatory or guideline limits. This work presents a streamlined approach for nuclear power facilities to develop three tiers of administrative limits for tritium in groundwater so that facilities can identify abnormal/uncontrolled releases of tritium at an early stage, and take appropriate actions to investigate, control, and protect groundwater. Tier 1 represents an upper limit of background, Tier 2 represents a level between background and Tier 3, and Tier 3 represents a risk-based concentration protective of down-gradient receptors. (author)

Determination of indoor radon concentration levels and the associated annual effective dose rate in some Ghanaian dwellings

International Nuclear Information System (INIS)

Nsiah-Akoto, I.

2010-01-01

Radon and its decay products in indoor air are the main source of natural internal irradiation of man. In this present work, the indoor radon concentration, the annual exposure, the annual effective dose and the annual dose equivalent to the lung received by the population were estimated in the dwellings at Dome in the Ga-East District of the Greater Accra Region, Ghana using time-integrated passive radon detectors; LR-115 Type II solid state nuclear track detector (SSNTD) technique. The primary objective of this project was to assess the annual effective dose rate due to the indoor radon concentration levels and the associated level of risk. Measurements were carried out from December 2009 to March 2010. After the 3 months exposure, the detectors were subjected to chemical etching in a 2.5M analytical grade sodium hydroxide solution at (60 ±1) o C, for 90mins in a constant temperature water bath to enlarge the latent tracks produced by alpha particles from the decay of radon. The etched tracks were magnified using the microfiche reader and counted with a tally counter. The mean indoor radon concentration was found to be (466.9±1.2) Bqm -3 and the mean annual exposure was (2.03±0.08) WLM. Assuming an indoor occupancy factor of 0.4 and 0.4 for equilibrium factor for radon indoors, we found out that the mean Rn-222 effective dose rate and the annual equivalent dose rate to the lung in the present study dwellings was (14.13±0.22)mSvy -1 and (3.74 E-07 ±3.50 E-06)Svy -1 respectively. The mean values of radon concentrations at Dome, Kwabenya, Biakpa, and South-Eastern part of Ghana, Prestea and Kassena-Nakana District in the previous research ranged from (9.4±0.5) to (518.7±4.0) Bqm -3 . The mean annual exposure, annual effective dose rate and the annual equivalent for the previous work ranged from (0.04±0.03)WLM to (0.58±0.05)WLM, (0.28±0.08) to (15.54±0.69mSvy -1 ), (8.23E-12±4.33E-07) to (4.15E-07± 1.13E-04) respectively. Odds ratios (ORs) for lung

Evaluation of toxicity after periocular and intravitreal administration of carboplatin in rabbit eyes

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Denisa Darsová

2011-01-01

Full Text Available The aim of this study was to characterize the extent of toxicity of focal carboplatin administration and to identify the dose limiting toxicity in rabbit eyes depending on administered concentrations. New Zealand white male rabbits (n = 18 were treated with 1 of 3 regimens: a single periocular injection of 15 mg of carboplatin (group I, a single periocular injection of 30 mg of carboplatin (group II and a single transcorneal intravitreal injection of 0.05 mg of carboplatin (group III. Ophthalmologic examinations and vitreous samplings were performed under dissociative anaesthesia at regular intervals during next 2 (groups I and III or 3 (group II weeks. Carboplatin concentrations in vitreous samples were assessed by atomic absorption spectroscopy. At the end of experiments, all rabbit eyes were obtained for histopathologic examination. Clinical and histological evidence of toxicity was graded into four grades according to anatomical structures of the rabbit eye. The dose limiting toxicity was reached in group II after periocular injection of 30 mg of carboplatin and in group III after intravitreal injection of 0.05 mg of carboplatin. No systemic toxicity was observed in any group. Focal carboplatin administration may decrease systemic exposure to this cytotoxic drug in the retinoblastoma treatment. This moreover suggests that focal carboplatin administration is a promising approach and challenge for advanced retinoblastoma chemotherapy.

Dose-Dependent Effect of Intravenous Administration of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Neonatal Stroke Mice

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Tanaka, Emi; Ogawa, Yuko; Mukai, Takeo; Sato, Yoshiaki; Hamazaki, Takashi; Nagamura-Inoue, Tokiko; Harada-Shiba, Mariko; Shintaku, Haruo; Tsuji, Masahiro

2018-01-01

Neonatal brain injury induced by stroke causes significant disability, including cerebral palsy, and there is no effective therapy for stroke. Recently, mesenchymal stem cells (MSCs) have emerged as a promising tool for stem cell-based therapies. In this study, we examined the safety and efficacy of intravenously administered human umbilical cord-derived MSCs (UC-MSCs) in neonatal stroke mice. Pups underwent permanent middle cerebral artery occlusion at postnatal day 12 (P12), and low-dose (1 × 104) or high-dose (1 × 105) UC-MSCs were administered intravenously 48 h after the insult (P14). To evaluate the effect of the UC-MSC treatment, neurological behavior and cerebral blood flow were measured, and neuroanatomical analysis was performed at P28. To investigate the mechanisms of intravenously injected UC-MSCs, systemic blood flowmetry, in vivo imaging and human brain-derived neurotrophic factor (BDNF) measurements were performed. Functional disability was significantly improved in the high-dose UC-MSC group when compared with the vehicle group, but cerebral blood flow and cerebral hemispheric volume were not restored by UC-MSC therapy. The level of exogenous human BDNF was elevated only in the cerebrospinal fluid of one pup 24 h after UC-MSC injection, and in vivo imaging revealed that most UC-MSCs were trapped in the lungs and disappeared in a week without migration toward the brain or other organs. We found that systemic blood flow was stable over the 10 min after cell administration and that there were no differences in mortality among the groups. Immunohistopathological assessment showed that the percent area of Iba1-positive staining in the peri-infarct cortex was significantly reduced with the high-dose UC-MSC treatment compared with the vehicle treatment. These results suggest that intravenous administration of UC-MSCs is safe for a mouse model of neonatal stroke and improves dysfunction after middle cerebral artery occlusion by modulating

Dose-Dependent Effect of Intravenous Administration of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Neonatal Stroke Mice

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Emi Tanaka

2018-03-01

Full Text Available Neonatal brain injury induced by stroke causes significant disability, including cerebral palsy, and there is no effective therapy for stroke. Recently, mesenchymal stem cells (MSCs have emerged as a promising tool for stem cell-based therapies. In this study, we examined the safety and efficacy of intravenously administered human umbilical cord-derived MSCs (UC-MSCs in neonatal stroke mice. Pups underwent permanent middle cerebral artery occlusion at postnatal day 12 (P12, and low-dose (1 × 104 or high-dose (1 × 105 UC-MSCs were administered intravenously 48 h after the insult (P14. To evaluate the effect of the UC-MSC treatment, neurological behavior and cerebral blood flow were measured, and neuroanatomical analysis was performed at P28. To investigate the mechanisms of intravenously injected UC-MSCs, systemic blood flowmetry, in vivo imaging and human brain-derived neurotrophic factor (BDNF measurements were performed. Functional disability was significantly improved in the high-dose UC-MSC group when compared with the vehicle group, but cerebral blood flow and cerebral hemispheric volume were not restored by UC-MSC therapy. The level of exogenous human BDNF was elevated only in the cerebrospinal fluid of one pup 24 h after UC-MSC injection, and in vivo imaging revealed that most UC-MSCs were trapped in the lungs and disappeared in a week without migration toward the brain or other organs. We found that systemic blood flow was stable over the 10 min after cell administration and that there were no differences in mortality among the groups. Immunohistopathological assessment showed that the percent area of Iba1-positive staining in the peri-infarct cortex was significantly reduced with the high-dose UC-MSC treatment compared with the vehicle treatment. These results suggest that intravenous administration of UC-MSCs is safe for a mouse model of neonatal stroke and improves dysfunction after middle cerebral artery occlusion by

Radioactivity concentration variation with depth and assessment of workers' doses in selected mining sites

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C.U. Nwankwo

2015-04-01

Full Text Available Mining workers are exposed to radiation in the process of extracting minerals from the earth crust. In this research, activity concentration of the radionuclides in samples collected at different depths in Komu (0–220 ft and Olode (0–30 ft mining sites, Oyo State, Nigeria and the associated workers' radiological risks were assessed. Gemstones from these sites are mined for local and international markets. The radionuclide contents of the samples were determined using Gamma spectroscopy technique. At Komu, 238U and 232Th concentrations, with few exceptions, increased with depth while that of 40K had no defined pattern. At Olode site, 238U and 232Th concentrations decreased with depth while that of 40K was almost constant. Internal hazard indices at Komu in some cases indicated an unacceptable level of risk to workers. Workers' doses would have been underestimated by between 12 and 55% if the activity concentrations of samples in the pit were not included in the calculation.

Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer.

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Fujioka, Rumi; Mochizuki, Nobuo; Ikeda, Masafumi; Sato, Akihiro; Nomura, Shogo; Owada, Satoshi; Yomoda, Satoshi; Tsuchihara, Katsuya; Kishino, Satoshi; Esumi, Hiroyasu

2018-01-01

Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle.

Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer.

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Rumi Fujioka

Full Text Available Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle.

Acute oral administration of low doses of methylphenidate targets calretinin neurons in the rat septal area.

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Alvaro eGarcía-Aviles

2015-03-01

Full Text Available Methylphenidate (MPD is a commonly administered drug to treat children suffering from attention deficit hyperactivity disorder (ADHD. Alterations in septal driven hippocampal theta rhythm may underlie attention deficits observed in these patients. Amongst others, the septo-hippocampal connections have long been acknowledged to be important in preserving hippocampal function. Thus, we wanted to ascertain if methylphenidate administration, which improves attention in patients, could affect septal areas connecting with hippocampus. We used low and orally administered methylphenidate doses (1.3; 2.7 and 5mg/Kg to rats what mimics the dosage range in humans. In our model, we observed no effect when using 1.3mg/Kg methylphenidate; whereas 2.7 and 5 mg/Kg induced a significant increase in c-fos expression specifically in the medial septum, an area intimately connected to the hippocampus. We analyzed dopaminergic areas such as nucleus accumbens and striatum, and found that only 5mg/Kg induced c-fos levels increase. In these areas tyrosine hydroxylase correlated well with c-fos staining, whereas in the medial septum the sparse tyrosine hydroxylase fibres did not overlap with c-fos positive neurons. Double immunofluorescence of c-fos with neuronal markers in the septal area revealed that co-localization with choline acethyl transferase, parvalbumin, and calbindin with c-fos did not change with MPD treatment; whereas, calretinin and c-fos double labeled neurons increased after MPD administration. Altogether, these results suggest that low and acute doses of methylphenidate primary target specific populations of caltretinin medial septal neurons.

[Creation of experimental emphysema by the intratracheal administration of papain].

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Basmadzhieva, K; Kolev, K; Balabaeva, L

1981-01-01

The authors formed lung emphysema in white rats under experimental conditions by intratracheal application of various concentrations of papaine at different intervals. In the performed experiment the most suitable dose for formation of emphysema was two fold administration of 2 milligrams of papaine. The following indices were observed in the experimental and control animals: body weight, weight coefficient of the internal organs, indices of lipid and nucleinic metabolism in homogenates of lung as well as histomorphologic examination of lung.

Measurement of Natural Radioactive Nuclide Concentrations and the Dose Estimation of Workers Originated from Radon in Manganese Ore Mine

International Nuclear Information System (INIS)

Mansour, N.A.; Hassan, N.M.; Blasy, M.R.

2013-01-01

Manganese ore is widely used in many industries. Such as ore contain natural radioactive nuclides at various concentrations. If this ore contain high concentrations of natural radioactive nuclides, workers handling them might be exposed to significant levels of radiation. Therefore it is important to determine the radioactive nuclides in this ore. Also the regulation of radon concentration at workplaces has gained an accentuated importance in all countries. Nevertheless, at this time there is no globally accepted workplace protocol that sets out safe radon concentration values. In this study the radon concentration measured by using an Alpha Guard radon monitor, the equilibrium factor which was greater than the value given in literature, effective radiation dose, which are necessary for the exact estimation of the radiation dose originating from radon. The regulation of radon concentration at workplaces has gained an accentuated importance in all countries. Approach: The natural radionuclides ( 238 U, 232 Th and 40 K) contents of manganese ore samples collected from Umm Bogma, southwest Sinai and from the mountain access Hamid South Eastern Desert, Egypt have been determined by low background spectroscopy using hyper-pure germanium (HPGe) detector. Results: The mean activities due to the three radionuclides ( 238 U, 232 Th and 40 K) were found to be 1500±65, 490±65 and 364±45 Bqkg -1 , respectively. The absorbed dose rate due to the natural radioactivity in samples under investigation ranged from 1522±45 → 1796±43 nGyh -1 . The radium equivalent activity varied from 3807±114→ 4446±133 Bqkg -1 .The representative external hazard index values for the corresponding samples are also estimated. Conclusion: The results of this assessment obtained by the gamma-ray spectroscopic analysis, have indicated that the levels of natural radioactivity were lower than the international recommended limits.

The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration.

Science.gov (United States)

Umigai, N; Murakami, K; Ulit, M V; Antonio, L S; Shirotori, M; Morikawa, H; Nakano, T

2011-05-15

Crocetin, a unique carotenoid with a short carbon chain length, is an active compound of saffron and Gardenia jasminoides Ellis used as traditional herbal medicine. The present study was undertaken to investigate the pharmacokinetic profiles of crocetin in healthy adult subjects. The study was conducted as an open-label, single dose escalation with 10 Filipino volunteers (5 men and 5 women). The subjects received a single dose of crocetin at three doses (7.5, 15 and 22.5 mg) in one week interval. Blood samples were collected from the brachial vein before and at 1, 2, 4, 6, 8, 10 and 24 h after administration. Plasma concentrations of crocetin were determined by high-performance liquid chromatography (HPLC). Crocetin was rapidly absorbed and detected within an hour of administration with a mean time to reach maximum concentration (T(max)) of crocetin ranging from 4.0 to 4.8 h. The mean values of C(max) and AUC(0-24h) ranged from 100.9 to 279.7 ng/ml and 556.5 to 1720.8 ng. h/ml respectively. C(max) and AUC values increased with dose proportional manner. Crocetin was eliminated from human plasma with a mean elimination half life (T(½) of 6.1 to 7.5 h. In summary, there were no serious adverse events up to 22.5 mg dose of crocetin while crocetin was found to be absorbed more quickly than the other carotenoids such as β-carotene, lutein and lycopene. Copyright © 2010 Elsevier GmbH. All rights reserved.

Striatal dopamine release in vivo following neurotoxic doses of methamphetamine and effect of the neuroprotective drugs, chlormethiazole and dizocilpine.

Science.gov (United States)

Baldwin, H A; Colado, M I; Murray, T K; De Souza, R J; Green, A R

1993-03-01

1. Administration to rats of methamphetamine (15 mg kg-1, i.p.) every 2 h to a total of 4 doses resulted in a neurotoxic loss of striatal dopamine of 36% and of 5-hydroxytryptamine (5-HT) in the cortex (43%) and hippocampus (47%) 3 days later. 2. Administration of chlormethiazole (50 mg kg-1, i.p.) 15 min before each dose of methamphetamine provided complete protection against the neurotoxic loss of monoamines while administration of dizocilpine (1 mg kg-1, i.p.) using the same dose schedule provided substantial protection. 3. Measurement of dopamine release in the striatum by in vivo microdialysis revealed that methamphetamine produced an approximate 7000% increase in dopamine release after the first injection. The enhanced release response was somewhat diminished after the third injection but still around 4000% above baseline. Dizocilpine (1 mg kg-1, i.p.) did not alter this response but chlormethiazole (50 mg kg-1, i.p.) attenuated the methamphetamine-induced release by approximately 40%. 4. Dizocilpine pretreatment did not influence the decrease in the dialysate concentration of the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) produced by administration of methamphetamine while chlormethiazole pretreatment decreased the dialysate concentration of these metabolites still further. 5. The concentration of dopamine in the dialysate during basal conditions increased modestly during the course of the experiment. This increase did not occur in chlormethiazole-treated rats. HVA concentrations were unaltered by chlormethiazole administration. 6. Chlormethiazole (100-1000 microM) did not alter methamphetamine (100 microM) or K+ (35 mM)-evoked release of endogenous dopamine from striatal prisms in vitro. 7. Several NMDA antagonists prevent methamphetamine-induced neurotoxicity; however chlormethiazole is not an NMDA antagonist. Inhibition of striatal dopamine function prevents methamphetamine-induced toxicity of both dopamine and 5

Optimizing lithium dosing in hemodialysis

DEFF Research Database (Denmark)

Bjarnason, N H; Munkner, R; Kampmann, J P

2006-01-01

We studied a 62-year-old female hemodialysis patient during initiation and maintenance of lithium carbonate therapy. Three different methods were applied to estimate the regimen: a scenario based on volume of distribution (V(d)), a scenario based on glomerular filtration rate (GFR), and a scenario...... estimates. Furthermore, the maintenance dose estimated from the central compartment (V1) led to plasma concentrations within the therapeutic range. Thus, a regimen where 12.2 mmol lithium was given after each hemodialysis session resulted in stable between-dialysis plasma lithium concentrations...... in this patient with no residual kidney function. We did not observe adverse effects related to this regimen, which was monitored from 18 days to 8 months of therapy, and the patient experienced relief from her severe depressive disorder. In conclusion, dialysis patients may be treated with lithium administrated...

Safety and PK/PD correlation of TV-1106, a recombinant fused human albumin-growth hormone, following repeat dose administration to monkeys.

Science.gov (United States)

Ashkenazi, Nurit; Rosenstock, Moti; Hallak, Hussein; Bassan, Merav; Rasamoelisolo, Michele; Leuschner, Jost; Shinar, Doron

TV-1106 is a recombinant human albumin genetically fused to growth hormone which is intended to reduce the frequency of injections for GH therapy users. We report the safety, tolerability, pharmacokinetics and pharmacodynamics of repeated subcutaneous injections of TV-1106 in Cynomolgus monkeys. Cynomolgus monkeys received four weekly subcutaneous injections of 0, 5, 10 or 20mg/kg TV-1106 and were monitored for safety signals throughout the study. Serum levels of TV-1106 and insulin-like growth factor 1 (IGF-1) were assayed. Treated animals showed no adverse effects or histopathological changes. TV-1106 serum concentrations showed sustained exposure to the drug. Exposure increased in a dose-dependent manner with peak concentrations at approximately 24h post-dosing and elimination half-lives in the range of 12 to 24h. IGF-1 serum concentrations were elevated throughout the entire study duration, indicative of the pharmacological response. There was a clear correlation between change in IGF-1 levels and dose or exposure to TV-1106. The safety, pharmacokinetic and pharmacodynamic findings support the further development of TV-1106 as a once-weekly administered treatment for patients with GHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Corneal pharmacokinetics of the 2% diacerein eye drops between multiple administration and single administration

Directory of Open Access Journals (Sweden)

Ke Yang

2018-04-01

Full Text Available AIM: To compare the pharmacokinetic differences of the 2% diacerein eye drops between conjunctival sac multiple administration and single administration in the cornea, and to provide the experimental basis for clinicians to use the conjunctival sac multiple administration.METHODS: Male Kunming mice were randomly divided into the multiple administration group and the single administration group. The multiple administration group were given diacerein eye drop every 2min(3 times in total. The concentrations of the metabolites of diacerein in the cornea were measured by high performance liquid chromatography after given eye drop 5, 15, 30, 60, 120, and 180min. The pharmacokinetic parameters were calculated by pharmacokinetic software(DAS2.1.1. RESULTS: The metabolites of diacerein, rhein, was detected in the cornea at each time point. The concentration of the metabolite of diacerein in the cornea was 318.678±40.88, 210.02±25.66, 188.83±31.74, 112.24±11.70, 90.28±22.01 and 57.67±13.71μg/g after given eye drop 5, 15, 30, 60, 120, and 180min in the multiple administration group. The concentration in the single administration group was 145.17±19.29, 97.95±10.49, 71.18±18.70, 39.11±2.44, 18.10±2.34 and 9.08±2.04μg/g respectively. The concentration of rhein in the cornea was the highest at 5min after the administration in the two groups. The concentration of the multiple administration group was higher than that in the single administration group at 5, 15, 30, 60, 120, and 180min(PCONCLUSION: Compared with the single administration, the conjunctival sac multiple administration has the advantages of high drug concentration and long duration. Therefor the conjunctival sac multiple administration is a more effective method to treat acute infectious corneal diseases.

{sup 14}C-Methylenebisphenylisocyanate ({sup 14}C-MDI). Study of absorption after single dermal and intradermal administration in rats

Energy Technology Data Exchange (ETDEWEB)

Leibold, E.; Hoffmann, H.D.; Hildebrand, B

1999-07-01

The absorption, distribution and excretion of radioactivity was studied in groups of four male Wistar rats following a single dermal and intradermal administration of {sup 14}C- Methylenebisphenylisocyanate ({sup 14}C-MDI) at nominal dose levels of 4.0 and 0.4 mg/cm{sup 2} for dermal administration and 0.4 mg/animal for intradermal administration. These dose levels nominally corresponded to 40 and 4.0 mg/animal for dermal administration. Considering the animal weights, dose levels corresponded to about 140 and 14 mg/kg body weight (dermal administration) and 1.4 mg/kg body weight (intradermal administration). In the experiments with dermal administration, animals were exposed for 8 hours and sacrificed 8, 24 or 120 h after beginning of exposure. In the experiment with intradermal administration, animals were sacrificed 120 h after treatment. After dermal administration of {sup 14}C-MDI, mean recoveries of radioactivity from all dose groups were in the range from 97.86 to 108.07% of the total radioactivity administered. Generally, the largest proportion of radioactivity was found at the application site and dressing. The total amount of radioactivity absorbed (including excreta, cage wash, tissues/organs and carcass) increased with increasing sacrifice time. Dermal absorption was very low and quantitatively similar at both dose levels; maximally ca. 0.9 % of the applied radioactivity was absorbed. After intradermal administration of {sup 14}C-MDI, the mean recovery of radioactivity was 100.90 % of the radioactivity administered. The largest proportion of radioactivity was found at the application site. The total amount of radioactivity absorbed (including excreta, cage wash, tissues/organs and carcass) amounted to about 26 % of the radioactivity applied. Irrespective of the mode of administration of 1{sup 4C}-MDI, concentrations of radioactivity in tissues and organs generally were below 1 {mu}g Eq/g at 120 h after administration. In summary, the results of this

Vitamin A status of Filipino preschool children given a massive oral dose.

Science.gov (United States)

Perlas, L A; Florentino, R F; Fuertes, R T; Madriaga, J R; Cheong, R L; Desnacido, J A; Marcos, J M; Cabrera, M I

1996-12-01

The protection period of a 200,000 IU of vitamin A on Filipino children was determined. Subjects were 105 children aged 1-5 years given a single massive dose during the "Araw ng Sangkap Pinoy" (ASAP) in March 1995. Serum retinol was measured by HPLC at baseline, one, two, four and six months after the administration of the dose. Results showed that baseline serum retinol levels were significantly lower than all follow-up values. Serum retinol values were maintained at levels higher than pre-supplementation values although the values decreased on the second month after supplementation. The proportions of deficient and low (values at baseline were significantly lower (p values. The WHO recommendation of 200,000 IU was effective in increasing serum retinol concentrations and maintaining it above pre-supplementation levels up to 6 months after administration of the dose. It also replenished organic vitamin A reserves as shown by the dose response (S30DR) approach. Incidence of infection also decreased among the children. Supplementation with vitamin A has likewise resulted in an increase in hemoglobin values and a decrease in the proportion of anemics (Hb < 11.0 g/dl) among the children.

An fMRI study on variation of visuospatial cognitive performance of young male due to highly concentrated oxygen administration

Science.gov (United States)

Chung, Soon Cheol; Kim, Ik Hyeon; Tack, Gye Rae; Sohn, Jin Hun

2004-04-01

This study investigated the effects of 30% oxygen administration on the visuospatial cognitive performance using fMRI. Eight college students (right-handed, average age 23.5) were selected as subjects for this study. Oxygen supply equipment which gives 21% and 30% oxygen at a constant rate of 8L/min was developed for this study. To measure the performance of visuospatial cognition, two questionnaires with similar difficulty containing 20 questions each were also developed. Experiment was designed as two runs: run for visuospatial cognition test with normal air (21% of oxygen) and run for visuospatial cognition test with highly concentrated air (30% of oxygen). Run consists of 4 blocks and each block has 8 control problems and 5 visuospatial problems. Functional brain images were taken from 3T MRI using single-shot EPI method. Activities of neural network due to performing visuospatial cognition test were identified using subtraction procedure, and activation areas while performing visuospatial cognition test were extracted using double subtraction procedure. Activities were observed at occipital lobe, parietal lobe, and frontal lobe when performing visuospatial cognition test following both 21% and 30% oxygen administration. But in case of only 30% oxygen administration there were more activities at left precuneus, left cuneus, right postcentral gyrus, bilateral middle frontal gyri, right inferior frontal gyrus, left superior frontal gyrus, bilateral uvula, bilateral pyramis, and nodule compared with 21% oxygen administration. From results of visuospatial cognition test, accuracy rate increased in case of 30% oxygen administration. Thus it could be concluded that highly concentrated oxygen administration has positive effects on the visuospatial cognitive performance.

Estimation of effective doses derived from radon in selected SPA centers that use geothermal waters based on the information of radon concentrations

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Katarzyna Walczak

2013-04-01

Full Text Available Background: Geothermal waters contain, among other components, soluble radon gas. Alpha radioactive radon is a health hazard to humans, especially when it gets into the respiratory tract. SPA facilities that use geothermal water can be a source of an increased radiation dose to people who stay there. Based on the available literature concerning radon concentrations, we assessed exposure to radon among people - workers and visitors of Spa centers that use geothermal waters. Material and Methods: Radon concentrations were analyzed in 17 geothermal centers: in Greece (3 centers, Iran (5, China (4 and India (5. Doses recived by people in the SPA were estimated using the formula that 1 hour exposure to 1 Bq/m3 of radon concentration and equilibrium factor F = 0.4 corresponds to an effective dose of 3.2 nSv. Results: We have found that radon levels in SPAs are from a few to several times higher than those in confined spaces, where geothermal waters are not used (e.g., residential buildings. In 82% of the analyzed SPAs, workers may receive doses above 1 mSv/year. According to the relevant Polish regulations, people receiving doses higher than 1 mSv/year are included in category B of radiation exposure and require regular dosimetric monitoring. Doses received by SPA visitors are much lower because the time of their exposure to radon released from geothermal water is rather short. Conclusions: The analysis of radon concentration in SPA facilities shows that the radiological protection of people working with geothermal waters plays an important role. It seems reasonable to include SPA workers staying close to geotermal waters into a dosimetric monitoring program. Med Pr 2013;64(2:193–198

Some radioactivity concentrations and ingestion dose projections arising from consumption of food containing Chernobyl contamination

International Nuclear Information System (INIS)

Paz, L.R. de la; Palattao, M.V.; Estacio, J.F.L.; Anden, A.

1987-04-01

Doses arising from the ingestion of radioactive contamination coming from Chernobyl accident are calculated using various radioactivity limits adopted by different organizations after the accident. These are compared with that allowed in the Philippines. Projected concentrations of Cs-137 and Cs-134 in various food items in the affected countries, one month and one year after the accident are calculated using a model proposed by Boone, Ng and Palms. Except for food produced in one or two hot spots, the projected concentrations after one year are expected to return to within the range of pre-Chernobyl values. (Auth.) 12 refs.; 13 tabs.; 6 figs

Toxicity of lead acetate to female rabbits after chronic subcutaneous administration. Pt. 1. Biochemical and clinical effects

Energy Technology Data Exchange (ETDEWEB)

Falke, H.E. (Nijverheidsorganisatie TNO, Zeist (Netherlands). Toxicology and Nutrition Inst.); Zwennis, W.C.M. (Nijverheidsorganisatie TNO, Rijswijk (Netherlands). Medical Biological Lab.)

1990-10-01

The effect of chronic subcutaneous administration of lead acetate was studied in female rabbits. The low-dose group (15 animals) received three times a week 0.10-0.20 {mu}g/kg body weight and the high-dose group (15 animals) 0.80-1.20 {mu}g/kg. The control group received the vehicle only. Concentrations of lead in blood in the low-dose group increased to ca. 400 {mu}g/l after 70 days and in the high-dose group to ca. 900 {mu}g/l after 110 days. After 7.5 months eight animals of each group were sacrificed. The remaining rabbits were kept for an additional 4 months without treatment. Blood lead concentrations decreased with a half-time of 60-70 days. During exposure the gain in body weight was lower in the high-dose group than in the control group and the low-dose group. The high-dose group developed slight anaemia and low MCV, MCH and MCHC, and basophilic stipping of erythrocytes. These effects disappeared during recovery. ALAD activity in erythrocytes was very low during exposure in both exposed groups and did not reach control values during recovery. During exposure the concentrations of ZPP and ALA-U increased, but only ALA-U returned to normal during recovery. No other effects of lead on the composition of the urine were observed. No effects were observed on plasma urea and creatinine concentrations. In the high-dose group the concentration of ALAD in the liver decreased by 30%. During recovery this effect was no longer present. No effects were seen in cytochrome P-450 content or cytochrome P-450-dependent enzyme activities. Lead was mainly stored in bones, but some also in several soft tissues. After recovery the concentrations in soft tissues decreased to a variable degree. In the high-dose group the relative weights of heart and liver increased. These effects disappeared during recovery. At 400 {mu}g lead/l blood no adverse effects were observed that did occur at the high dose level. (orig.).