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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

Steady-State Serum T3 Concentrations for 48 Hours Following the Oral Administration of a Single Dose of 3,5,3'-Triiodothyronine Sulfate (T3S).

Science.gov (United States)

Santini, Ferruccio; Giannetti, Monica; Ricco, Ilaria; Querci, Giorgia; Saponati, Giorgio; Bokor, Daniela; Rivolta, Giovanni; Bussi, Simona; Braverman, Lewis E; Vitti, Paolo; Pinchera, Aldo

2014-07-01

Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A desulfating pathway reverses this process, and thyromimetic effects have been observed following the parenteral administration of 3,5,3'-triiodothyronine (T3) sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of T3. Twenty-eight hypothyroid patients (7 men and 21 women; mean age, 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T3) prior to 131I remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group), or 160 μg (16 patients/group) of T3S was administered 3 days before the planned administration of 131I. Blood samples for serum T3S and total T3 (TT3) concentrations were obtained at various times up to 48 hours after T3S administration. At all T3S doses, serum T3S concentrations increased, reaching a peak at 2 to 4 hours and progressively returning to basal levels within 8 to 24 hours. The T3S maximum concentration (Cmax) and area under the 0- to 48-hour concentration-time curve (AUC0-48h) were directly and significantly related to the administered dose. An increase in serum TT3 concentration was observed (significant after 1 hour), and the concentration increased further at 2 and 4 hours and then remained steady up to 48 hours after T3S administration. There was a significant direct correlation between the TT3 AUC0-48h and the administered dose of T3S. No changes in serum free thyroxine (T4) concentrations during the entire study period were observed, whereas serum thyroid-stimulating hormone levels increased slightly at 48 hours, but this was not related to the dose of T3S. No adverse events were reported. (1) T3S is

Effects of Oral Administration of Nicotine on Organ Weight, Serum ...

African Journals Online (AJOL)

This study investigated the effects of oral administration of nicotine on body and reproductive organ weight, serum testosterone level and testicular histology in adult male rats. Forty male rats divided into five groups and treated for a period of 30 days with 0.5mg/kg (low dose) and 1.0mg/kg (high dose) body weight of ...

Serum concentrations of buprenorphine after oral and parenteral administration in male mice

DEFF Research Database (Denmark)

Kalliokoski, Otto; Jacobsen, Kirsten R; Hau, Jann

2011-01-01

Buprenorphine is the most commonly used drug for peri-operative pain relief in laboratory rodents. The systemic concentrations of buprenorphine were measured in mice following administration intravenously (IV), subcutaneously (SC), orally by gavage and by voluntary ingestion, to determine the post-administration...... serum concentration of buprenorphine. Voluntarily ingested buprenorphine resulted in long-lasting high serum concentrations, as did oral gavage administration (24h serum concentration: 110ngh/mL for both routes of administration). In contrast, buprenorphine administered parenterally remained...... in the circulation for a substantially shorter time (24h serum concentration for IV and SC were 40ngh/mL and 30ngh/mL, respectively). This marked difference was probably due to the higher dose used for oral administration, which is regarded necessary for sufficient analgesic effect, and to the slower absorption...

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

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

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.

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

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

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

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.

Pharmacokinetics of guaifenesin following administration of multiple doses to exercised Thoroughbred horses.

Science.gov (United States)

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

2016-08-01

Guaifenesin is an expectorant commonly used in performance horses to aid in the clearance of mucus from the airways. Guaifenesin is also a centrally acting skeletal muscle relaxant and as such is a prohibited drug with withdrawal necessary prior to competition. To the authors' knowledge, there are no reports in the literature describing single or multiple oral administrations of guaifenesin in the horse to determine a regulatory threshold and related withdrawal time. Therefore, the objective of the current study was to describe the pharmacokinetics of guaifenesin following oral administration in order to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 2 g of guaifenesin orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum guaifenesin concentrations were determined and pharmacokinetic parameters calculated. Guaifenesin was rapidly absorbed (Tmax of 15 min) following oral administration. The Cmax was 681.3 ± 323.8 ng/mL and 1080 ± 732.8 following the first and last dose, respectively. The serum elimination half-life was 2.62 ± 1.24 h. Average serum guaifenesin concentrations remained above the LOQ of the assay (0.5 ng/mL) by 48 h postadministration of the final dose in 3 of 9 horses. © 2016 John Wiley & Sons Ltd.

Studies on the absorption of iron after oral administration in piglets

International Nuclear Information System (INIS)

Thoren-Tolling, K.

1975-01-01

72 newborn piglets from 9 litters were used to determinate the retention and distribution in the body of labelled iron given either orally as ferrous fumarate (100 mg Fe 2+ ) or iron dextran (200 mg Fe 3+ ), or by injection as iron dextran (100 mg Fe 3+ ). About 25-30 % of the radioiron from a single oral dose of labelled ferrous fumarate (100 mg Fe 2+ ), and about 55-60 % from a single oral dose of labelled iron dextran (200 mg Fe 3+ ) were absorbed by the body. As iron is excreted throughout the experiment, only about 20% and 40-50% respectively of the radio-iron from these iron compounds were recovered 3 weeks after treatment. The total amounts of labelled iron retained in the body after oral administration of the same doses of these iron compounds, alone or in combination, were compared. A slight retardation of the absorption of ferrous iron was observed when iron dextran was administered simultaneeously. The absorption of iron dextran was not influenced by the simultaneous administration of ferrous fumarate. The importance of the liver as the main iron storage site was shown, and the rapid utilization of iron from storage sites, about 2-3 weeks after treatment was demonstrated. The concentration of labelled iron in urine and some lymphglands was measured. Only minute quantities of radio-iron were excreted in the urine throughout the entire experiment. The lymph nodes seem to act as iron stones after administration of iron dextran. The importance of the lymphatic tissue in absorption and storage of labelled iron is discussed. (author)

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

Science.gov (United States)

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

The engagement of oral-associated lymphoid tissues during oral versus gastric antigen administration.

Science.gov (United States)

Bankvall, Maria; Östberg, Anna-Karin; Jontell, Mats; Wold, Agnes; Östman, Sofia

2016-09-01

The role of oral-associated lymphoid tissues during induction of oral tolerance still remains elusive. Therefore, the aim was to compare T-cell activation and induction of tolerance to ovalbumin (OVA) presented through either of two routes; deposited into the oral cavity, or the stomach, thereby bypassing the oral cavity. OVA was administered by the oral or gastric route to BALB/c mice that had received OVA-specific DO11.10+ CD4(+) T cells, stained with CellTrace(™) Violet dye, through intravenous injection. Proliferating OVA-specific T cells were detected in the nose-associated lymphoid tissues (NALT) and the cervical, mesenteric and peripheral lymph nodes at different time-points following OVA exposure. OVA-specific T-cell proliferation was initially observed in the NALT 1 hr after oral, but not gastric, administration. However, at day 1, proliferation at this site was also detected after gastric administration and profound proliferation was observed at all sites by day 4. For the oral route the degree of proliferation observed was lower in the peripheral lymph nodes by day 4 compared with the other sites. These results demonstrate a similar activation pattern achieved by the two routes. However, the NALT distinguishes itself as a site of rapid T-cell activation towards fed antigens irrespective of feeding regimen. To evaluate induction of tolerance a semi-effective OVA dose was used, to detect differences in the degree of tolerance achieved. This was performed in a model of OVA-induced airway hypersensitivity. No differences in tolerance induction were observed between the two administration routes. © 2016 John Wiley & Sons Ltd.

Morning administration of oral methamphetamine dose-dependently disrupts nighttime sleep in recreational stimulant users.

Science.gov (United States)

Herrmann, Evan S; Johnson, Patrick S; Bruner, Natalie R; Vandrey, Ryan; Johnson, Matthew W

2017-09-01

Use of amphetamine-type stimulants (e.g., methamphetamine) is associated with acute sleep disruptions. No prior reports have characterized the acute effects of methamphetamine on sleep using polysomnography, the gold standard for objective sleep monitoring. Recreational stimulant users (n=19) completed a baseline assessment, which included questionnaires assessing demographic and substance use characteristics, and the Pittsburgh Sleep Quality Index (PSQI), which assesses sleep quality over the past month. Participants were administered 0mg (placebo), 20mg, or 40mg oral methamphetamine at 08:15h on study days, using a double-blind, randomized, within-subjects design. Sleep was monitored using polysomnography from 22:20 that evening until 06:15 the following morning. PSQI scores indicated more than half of participants reported poor sleep quality at baseline. Methamphetamine dose-dependently increased sleep latency, and decreased total sleep time, sleep efficiency, time in NREM 2 sleep, number of REM periods, and total time in REM sleep. Sleep under placebo conditions was consistent with what would be expected from healthy adults. Morning oral administration of methamphetamine produces robust disruptions in nighttime sleep. Future research should examine relations between stimulant use and sleep disruption in naturalistic settings, with regard to both stimulant abuse and licit prescription use. Copyright © 2017. Published by Elsevier B.V.

Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses.

Science.gov (United States)

Linardi, Renata L; Stokes, Ashley M; Keowen, Michael L; Barker, Steven A; Hosgood, Giselle L; Short, Charles R

2012-02-01

To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses. 6 healthy adult horses. Horses received single doses (each 0.15 mg/kg) of an oral formulation of methadone hydrochloride orally or intragastrically or an injectable formulation of the drug orally, intragastrically, or IV (5 experimental treatments/horse; 2-week washout period between each experimental treatment). A blood sample was collected from each horse before and at predetermined time points over a 360-minute period after each administration of the drug to determine serum drug concentration by use of gas chromatography-mass spectrometry analysis and to estimate pharmacokinetic parameters by use of a noncompartmental model. Horses were monitored for adverse effects. In treated horses, serum methadone concentrations were equivalent to or higher than the effective concentration range reported for humans, without induction of adverse effects. Oral pharmacokinetics in horses included a short half-life (approx 1 hour), high total body clearance corrected for bioavailability (5 to 8 mL/min/kg), and small apparent volume of distribution corrected for bioavailability (0.6 to 0.9 L/kg). The bioavailability of methadone administered orally was approximately 3 times that associated with intragastric administration. Absorption of methadone in the small intestine in horses appeared to be limited owing to the low bioavailability after intragastric administration. Better understanding of drug disposition, including absorption, could lead to a more appropriate choice of administration route that would enhance analgesia and minimize adverse effects in horses.

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.

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....

Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia.

Science.gov (United States)

Poncin, Marc; Zulu, Gideon; Voute, Caroline; Ferreras, Eva; Muleya, Clara Mbwili; Malama, Kennedy; Pezzoli, Lorenzo; Mufunda, Jacob; Robert, Hugues; Uzzeni, Florent; Luquero, Francisco J; Chizema, Elizabeth; Ciglenecki, Iza

2018-02-01

To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting. In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose. We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.

Non-randomized study on the effects of preoperative radiotherapy and daily administration of low-dose cisplatin against those of radiotherapy alone for oral cancer. Effects on local control, control of metastases, and overall survival

International Nuclear Information System (INIS)

Kurita, Hiroshi; Ohtsuka, Akiko; Kobayashi, Hiroichi; Kurashina, Kenji; Shikama, Naoto; Oguchi, Masahiko

2000-01-01

Cisplatin is a known radiation modifier. Our previous study suggested that daily administration of low-dose cisplatin enhanced the efficacy of radiotherapy against primary oral squamous carcinoma. In this paper, we follow the patients who participated in the previous study and survey the benefit of combination low-dose cisplatin in improving local control, prevention of metastases, and overall survival. This study included patients with surgically resectable advanced oral tumors. Ten patients underwent preoperative radiotherapy of 30-40 Gy/15-20 days with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten other patients received external radiotherapy alone. All patients then underwent a planned radical tumor resection. No significant difference was see in loco-regional control rates (primary: 86 vs. 88%, neck: 83 vs. 78% at 48 months) or incidence of metastasis (70 vs. 64%) between the two groups. Nor was there a significant difference in the overall survival rate (60 vs. 66%). The results of this study suggest that the concomitant use of daily administration of low-dose cisplatin with preoperative radiation brings no statistically significant benefit in improving local control and survival rate in patients with advanced resectable oral cancer. (author)

Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis

NARCIS (Netherlands)

Hoekstra, Monique; Haagsma, C.; Neef, C; Proost, Johannes H; Knuif, A.; van der Laar, M.

Objective. To determine the bioavailability of higher oral doses of methotrexate (MTX) in adult patients with rheumatoid arthritis (RA). Methods. A pharmacokinetic analysis was performed in 15 patients with RA taking a stable dose of MTX (greater than or equal to25 mg weekly). Separated by 2 weeks,

Effect of Oral Administration of “Gadagi” Tea on Lipid Profile in Rats ...

African Journals Online (AJOL)

Abstract: Effect of oral administration of “Gadagi” tea on lipid profile was assessed in 50 healthy male albino rats which were grouped and administered with different doses(mg/kg) i.e low dose (380mg/kg, 415mg/kg, 365mg/kg,. 315mg/kg for “sak”, ”sada” and “magani” respectively), standard dose (760mg/kg, 830mg/kg, ...

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

Science.gov (United States)

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

2013-10-01

The pharmacokinetic profile of meloxicam in clinically healthy koalas (n = 15) was investigated. Single doses of meloxicam were administered intravenously (i.v.) (0.4 mg/kg; n = 5), subcutaneously (s.c.) (0.2 mg/kg; n = 1) or orally (0.2 mg/kg; n = 3), and multiple doses were administered to two groups of koalas via the oral or s.c. routes (n = 3 for both routes) with a loading dose of 0.2 mg/kg for day 1 followed by 0.1 mg/kg s.i.d for a further 3 days. Plasma meloxicam concentrations were quantified by high-performance liquid chromatography. Following i.v. administration, meloxicam exhibited a rapid clearance (CL) of 0.44 ± 0.20 (SD) L/h/kg, a volume of distribution at terminal phase (Vz ) of 0.72 ± 0.22 L/kg and a volume of distribution at steady state (Vss ) of 0.22 ± 0.12 L/kg. Median plasma terminal half-life (t(1/2)) was 1.19 h (range 0.71-1.62 h). Following oral administration either from single or repeated doses, only maximum peak plasma concentration (C(max) 0.013 ± 0.001 and 0.014 ± 0.001 μg/mL, respectively) was measurable [limit of quantitation (LOQ) >0.01 μg/mL] between 4-8 h. Oral bioavailability was negligible in koalas. Plasma protein binding of meloxicam was ~98%. Three meloxicam metabolites were detected in plasma with one identified as the 5-hydroxy methyl derivative. This study demonstrated that koalas exhibited rapid CL and extremely poor oral bioavailability compared with other eutherian species. Accordingly, the currently recommended dose regimen of meloxicam for this species appears inadequate. © 2013 John Wiley & Sons Ltd.

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

Directory of Open Access Journals (Sweden)

Gabriela A. Albarellos

2013-10-01

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

Antinociceptive effects after oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

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Sanchez-Migallon Guzman, David; Souza, Marcy J; Braun, Jana M; Cox, Sherry K; Keuler, Nicholas S; Paul-Murphy, Joanne R

2012-08-01

To evaluate antinociceptive effects on thermal thresholds after oral administration of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). Animals-15 healthy adult Hispaniolan Amazon parrots. 2 crossover experiments were conducted. In the first experiment, 15 parrots received 3 treatments (tramadol at 2 doses [10 and 20 mg/kg] and a control suspension) administered orally. In the second experiment, 11 parrots received 2 treatments (tramadol hydrochloride [30 mg/kg] and a control suspension) administered orally. Baseline thermal foot withdrawal threshold was measured 1 hour before drug or control suspension administration; thermal foot withdrawal threshold was measured after administration at 0.5, 1.5, 3, and 6 hours (both experiments) and also at 9 hours (second experiment only). For the first experiment, there were no overall effects of treatment, hour, period, or any interactions. For the second experiment, there was an overall effect of treatment, with a significant difference between tramadol hydrochloride and control suspension (mean change from baseline, 2.00° and -0.09°C, respectively). There also was a significant change from baseline for tramadol hydrochloride at 0.5, 1.5, and 6 hours after administration but not at 3 or 9 hours after administration. Tramadol at a dose of 30 mg/kg, PO, induced thermal antinociception in Hispaniolan Amazon parrots. This dose was necessary for induction of significant and sustained analgesic effects, with duration of action up to 6 hours. Further studies with other types of noxious stimulation, dosages, and intervals are needed to fully evaluate the analgesic effects of tramadol hydrochloride in psittacines.

Halloysite Nanotubes-Induced Al Accumulation and Fibrotic Response in Lung of Mice after 30-Day Repeated Oral Administration.

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Wang, Xue; Gong, Jiachun; Rong, Rui; Gui, Zongxiang; Hu, Tingting; Xu, Xiaolong

2018-03-21

Natural halloysite (Al 2 Si 2 O 5 (OH) 4 · nH 2 O) nanotubes (HNT) are clay materials with hollow tubular structure and are widely applied in many fields. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility; however, the in vivo toxicity of HNTs remains unclear. In this study, the biodistribution and pulmonary toxicity of the purified HNTs in mice were investigated after intragastric administration for 30 days. HNTs have high stability in biological conditions. Oral administration of HNTs caused significant Al accumulation predominantly in the lung with relative slight effects on Si biodistribution. Oral administration of HNTs stimulated the growth of the mice at low dose (5 mg/kg BW) with no pulmonary toxicity but inhibited the mouse growth and resulted in oxidative stress and inflammation in lung at high dose (50 mg/kg BW). In addition, oral HNTs at high dose could be absorbed from the gastrointestinal tract and deposited in lung and could also induce pulmonary fibrosis.

Extensive metabolism and route-dependent pharmacokinetics of bisphenol A (BPA) in neonatal mice following oral or subcutaneous administration

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Draganov, Dragomir I.; Markham, Dan A.; Beyer, Dieter; Waechter, John M.; Dimond, Stephen S.; Budinsky, Robert A.; Shiotsuka, Ronald N.; Snyder, Stephanie A.; Ehman, Kimberly D.; Hentges, Steven G.

2015-01-01

Orally administered bisphenol A (BPA) undergoes efficient first-pass metabolism to produce the inactive conjugates BPA-glucuronide (BPA-G) and BPA-sulfate (BPA-S). This study was conducted to evaluate the pharmacokinetics of BPA, BPA-G and BPA-S in neonatal mice following the administration of a single oral or subcutaneous (SC) dose. This study consisted of 3 phases: (1) mass-balance phase in which effective dose delivery procedures for oral or SC administration of 3 H-BPA to postnatal day three (PND3) mice were developed; (2) pharmacokinetic phase during which systemic exposure to total 3 H-BPA-derived radioactivity in female PND3 mice was established; and (3) metabolite profiling phase in which 50 female PND3 pups received either a single oral or SC dose of 3 H-BPA. Blood was collected from 5 pups/route/time-point at various times post-dosing, the blood plasma samples were pooled by group, and time-point and samples were profiled by HPLC with fraction collection. Fractions were analyzed for total radioactivity and data used to reconstruct radiochromatograms and to integrate individual peaks. The identity of the BPA, BPA-G, and BPA-S peaks was confirmed using authentic standards and LC–MS/MS analysis. The result of this study revealed that female PND3 mice have the capacity to metabolize BPA to BPA-G, BPA-S and other metabolites after both routes of administration. Systemic exposure to free BPA is route-dependent as the plasma concentrations were lower following oral administration compared to SC injection

Reducing radiation exposure during oral I-131 therapy administration

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Trujillo, J.; Krinsky, S.; Wilson, B.; Teague, E.

1982-01-01

A new, closed-system method to reduce air-, direct-, and incidental-contamination during therapeutic administration of oral I-131 was experimentally evaluated on twelve patients. We studied a standard control population using the routine practice of drinking the solution through a straw and compared results with our new technique. Various measurements were performed throughout all phases of dose administration to assess the relative difference of the two approaches. Using the closed system method before and during iodine administration revealed between 100 and 1000 times less activity per millimeter of air sample; whereas, the direct radiation exposure values were higher for the control population. Both the experimental and control methods had similar levels of incidental contamination

Evaluation of Cardiopulmonary Toxicity Following Oral Administration of Multi-walled Carbon Nanotubes in Wistar Rats

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Ehsan Zayerzadeh

2016-07-01

Full Text Available Objective(s: Carbon nanotubes have unique mechanical, electrical, and thermal properties, with potential different applications in nanomedicine, electronics, and other industries. These new applications of carbon nanotubes in different industries lead to the increased exposure risk of nanomaterials to human. Up to now, all aspects of carbon nanotubes toxicity are not completely clear following human and animal exposures with these novel compounds. The aim of this study was to assess cardiopulmonary toxicity of multi-walled carbon nanotubes following oral administration in rats with respect to the histopathological and biochemical evaluation. Methods: In the present investigation, we studied cardiorespiratory toxicity of multi-wall carbon nanotubes (MWCNT with regard to histopathological changes and some biomarkers including TnT, CK-MB and LDH in experimental rats following oral administration. One dose per 24 h of MWCNT suspension was administered orally (gavage technique to animals at the doses of 500, 1000 and 2000 mg/kg/day BW for 5 days. Results: The results of these study showed oral administration of MWCNT induces histopathological complications such as severe alveolar edema and hemorrhage in lungs and myocytolysis in heart of all experimental groups of animals. In all of the groups, troponin T level showed no changes when compared to baseline. Lactate dehydrogenase and CK-MB activity showed significant increment in all of animal groups following oral administration of carbon nanotubes. Conclusions: It can be concluded that oral exposure of MWCNT may be toxic for cardiovascular and respiratory systems, because MWCNT induced biochemical alterations and histopathological abnormalities in these vital systems.

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

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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

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

Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal Uptake of Acyclovir Following Oral Dosing

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Ravi S.Talluri

2009-10-01

Full Text Available Objective: To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV in rats. Methods: Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV, L-valine- D-valine-acyclovir (LDACV and D-valine-L-valine acyclovir (DLACV prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results: Following i.v. administration, the area under the curve (AUC in µM*min of generated ACV was in the order of LACV › LDACV › DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 µM*min, respectively. DLACV exhibited poor oral absorption. Cmax (µM and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions: LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV. Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.

Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal Uptake of Acyclovir Following Oral Dosing

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

2009-01-01

Objective To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV) in rats. Methods Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV), L-valine-D-valine-acyclovir (LDACV) and D-valine-L-valine acyclovir (DLACV) prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results Following i.v. administration, the area under the curve (AUC) in μM*min of generated ACV was in the order of LACV > LDACV > DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 μM*min, respectively. DLACV exhibited poor oral absorption. Cmax (μM) and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV. Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration. PMID:23861607

Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir following Intravenous and Oral Administrations in Rats: A study Involving in vivo corneal Uptake of Acyclovir following Oral Dosing

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Ravi S. Talluri

2009-01-01

Full Text Available Objective To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV in rats. Methods Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV, L-valine-D-valine-acyclovir (LDACV and D-valine-L-valine acyclovir (DLACV prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results Following i.v. administration, the area under the curve (AUC in μM*min of generated ACV was in the order of LACV > LDACV > DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 μM*min, respectively. DLACV exhibited poor oral absorption. C max (μM and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.

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.

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

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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

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

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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

Promotion or suppression of experimental metastasis of B16 melanoma cells after oral administration of lapachol

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Maeda, Masayo; Murakami, Manabu; Takegami, Tsutomu; Ota, Takahide

2008-01-01

Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] is a vitamin K antagonist with antitumor activity. The effect of lapachol on the experimental metastasis of murine B16BL6 melanoma cells was examined. A single oral administration of a high toxic dose of lapachol (80-100 mg/kg) 6 h before iv injection of tumor cells drastically promoted metastasis. This promotion of metastasis was also observed in T-cell-deficient mice and NK-suppressed mice. In vitro treatment of B16BL6 cells with lapachol promoted metastasis only slightly, indicating that lapachol promotes metastasis primarily by affecting host factors other than T cells and NK cells. A single oral administration of warfarin, the most commonly used vitamin K antagonist, 6 h before iv injection of tumor cells also drastically promoted the metastasis of B16BL6 cells. The promotion of metastasis by lapachol and warfarin was almost completely suppressed by preadministration of vitamin K3, indicating that the promotion of metastasis by lapachol was derived from vitamin K antagonism. Six hours after oral administration of lapachol or warfarin, the protein C level was reduced maximally, without elongation of prothrombin time. These observations suggest that a high toxic dose of lapachol promotes metastasis by inducing a hypercoagulable state as a result of vitamin K-dependent pathway inhibition. On the other hand, serial oral administration of low non-toxic doses of lapachol (5-20 mg/kg) weakly but significantly suppressed metastasis by an unknown mechanism, suggesting the possible use of lapachol as an anti-metastatic agent

Effects of Oral Prednisone Administration on Serum Cystatin C in Dogs.

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Muñoz, J; Soblechero, P; Duque, F J; Macías-García, B; Ruiz, P; Zaragoza, C; Barrera, R

2017-11-01

Oral administration of glucocorticoid alters serum cystatin C (sCysC) concentration in humans. To determine if oral administration of prednisone alters sCysC in dogs without pre-existing renal disease. Forty six dogs were included: 10 dogs diagnosed with steroid responsive meningitis arteritis (SRMA; group A), 20 dogs diagnosed of pituitary-dependent hyperadrenocorticism (PDH; group B), and 16 healthy control dogs (group C). Retrospective observational study. SRMA diagnosed dogs were administered prednisone 4 mg/kg/24 h PO 7 days, reducing the dose to 2 mg/kg/24 h 7 days before medication withdrawal. In group A, sampling was performed at days 0, 7, 14 and a final control at day 21. Blood and urine samples were collected in the 3 groups, and in group A, sampling was performed at all time points (days 1, 7, 14, and 21). In group A, sCysC was significantly higher at day 7 compared to the control group (0.4 ± 0.04 mg/L vs. 0.18 ± 0.03 mg/L mean ± SEM respectively P 0.05). Dogs with PDH included in group B did not have significant differences in sCysC (0.22 ± 0.03 mg/L) compared to control (P > 0.05). Oral administration of prednisone unlike altered endogenous glucocorticoid production, increases sCysC in dogs in a dose-dependent fashion. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Excretion and metabolism of 1-nitropyrene in rats after oral or intraperitoneal administration

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Dutcher, J.S.; Sun, J.D.; Bechtold, W.E.; Unkefer, C.J.

1985-01-01

The metabolism and excretion of 1-nitropyrene (NP), a prevalent NPAH, by Fischer-344 rats after intraperitoneal (ip) or oral administration was studied. Radiolabeled NP was administered to rats (10 mg NP/kg body wt), and urine and feces were collected for 7 days. After ip administration of [ 14 C]NP, 60% of the radioactivity was found in the urine and 20% in the feces. Likewise, 55 and 35% of the orally administered 14 C was found in urine and feces, respectively. Both urine and feces were analyzed by high-pressure liquid chromatography for metabolites. The majority of the radioactivity in both urine and feces was associated with very polar metabolites, none accounting for more than 10% of the dose. Small amounts (less than 1% of the dose) of aminopyrene (AP), acetylaminopyrene, and NP were detected. A urinary metabolite (3-8% of the dose) was found that converted to acetylaminopyrene phenol (two isomers) when urine was heated overnight at 37 0 C at pH 4.5. More of this metabolite (2.2 times) as well as AP (1.8 times), was excreted after oral than after ip administration of NP. The NP metabolites found in this study demonstrate that reduction of the nitro group is a significant route of NP metabolism in rats. Since nitroreduction appears to be necessary in the activation of NPAHs to bacterial mutagens, this indicates that similar metabolic pathways are present in rats (catalyzed by mammalian and/or gut bacterial enzymes) and that activation of NPAHs to carcinogens or toxins by nitroreduction is possible. 29 references, 8 figures

Oral administration of piperine for the control of aflatoxin intoxication in rats.

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Gagini, Thalita B; Silva, Robson E; Castro, Isabela S; Soares, Breno A; Lima, Marco E F; Brito, Marilene F; Mazur, Carlos; Direito, Glória M; Danelli, Maria das Graças M

2010-04-01

Aflatoxins are mycotoxins that have important toxic effects on human and animal health, even if consumed at low doses. The oral administration of piperine (1.12 mg/kg) during 23 days in rats seemingly interfered with the toxicity of aflatoxins, decreasing hepatic injuries and the leukocyte depletion in experimentally intoxicated animals.

Two cases of "cannabis acute psychosis" following the administration of oral cannabis

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Pin Marie

2005-04-01

Full Text Available Abstract Background Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users. Case presentations We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented. Conclusion While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur.

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

Thallium-201 myocardial imaging during pharmacologic coronary vasodilation: comparison of oral and intravenous administration of dipyridamole

International Nuclear Information System (INIS)

Taillefer, R.; Lette, J.; Phaneuf, D.C.; Leveille, J.; Lemire, F.; Essiambre, R.

1986-01-01

Although the diagnostic utility of thallium-201 myocardial imaging after dipyridamole infusion is well established, the intravenous form of the drug is not yet commercially available in North America. Fifty patients referred for coronary angiography were prospectively studied. Within a 2 week period, each patient underwent cardiac catheterization and thallium-201 myocardial imaging after both oral and intravenous dipyridamole administration. For the oral protocol, patients were randomly assigned to treatment with either 200 or 400 mg of dipyridamole in tablet form. Coronary artery stenoses of 70% or greater were considered significant. For the 25 patients who received a 200 mg oral dose of dipyridamole, the scintigraphic study showed perfusion defects in 65% of patients with significant coronary artery disease after the oral dose and in 85% of patients after the intravenous dose. For the 25 patients who received a 400 mg oral dose, the sensitivity of the scintigram was 84% after the oral dose and 79% after the intravenous dose. Except for headache and nausea, side effects were less severe and less frequent with oral (either 200 or 400 mg) than with intravenous dipyridamole. Because of the delayed and variable absorption of dipyridamole tablets, the oral studies required a longer period of medical supervision (45 to 60 minutes), and aminophylline was empirically administered after completion of the first set of thallium-201 images. It is concluded from this study that thallium-201 myocardial imaging after coronary vasodilation with a 400 mg oral dose of dipyridamole is a safe, widely available and reliable alternative for the evaluation of coronary artery disease in patients unable to achieve an adequate exercise level on stress testing

Effect of titanium dioxide nanoparticles on the cardiovascular system after oral administration.

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Chen, Zhangjian; Wang, Yun; Zhuo, Lin; Chen, Shi; Zhao, Lin; Luan, Xianguo; Wang, Haifang; Jia, Guang

2015-12-03

Titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various consumer products, especially food and personal care products. Compared to the well-characterized adverse cardiovascular effect of inhaled ambient ultrafine particles, research on the health response to orally administrated TiO2 NPs is still limited. In our study, we performed an in vivo study in Sprague-Dawley rats to understand the cardiovascular effect of TiO2 NPs after oral intake. After daily gastrointestinal administration of TiO2 NPs at 0, 2, 10, 50 mg/kg for 30 and 90 days, heart rate (HR), blood pressure, blood biochemical parameters and histopathology of cardiac tissues was assessed to quantify cardiovascular damage. Mild and temporary reduction of HR and systolic blood pressure as well as an increase of diastolic blood pressure was observed after daily oral administration of TiO2 NPs for 30 days. Injury of cardiac function was observed after daily oral administration of TiO2 NPs for 90 days as reflected in decreased activities of lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH) and creatine kinase (CK). Increased white blood cells count (WBC) and granulocytes (GRN) in blood as well as increased concentrations of tumor necrosis factor α (TNF α) and interleukin 6 (IL-6) in the serum indicated inflammatory response initiated by TiO2 NPs exposure. It was hypothesize that cardiac damage and inflammatory response are the possible mechanisms of the adverse cardiovascular effects induced by orally administrated TiO2 NPs. Data from our study suggested that even at low dose of TiO2 NPs can induce adverse cardiovascular effects after 30 days or 90 days of oral exposure, thus warranting concern for the dietary intake of TiO2 NPs for consumers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

Conscious sedation by oral administration of midazolam in paediatric dental treatment.

Science.gov (United States)

Erlandsson, A L; Bäckman, B; Stenström, A; Stecksén-Blicks, C

2001-01-01

Midazolam is a short-acting benzodiazepine with rapid onset, short duration of action and minimal side effects. The aim of this study was to evaluate the oral administration of midazolam as pre-operative sedation in the dental treatment of uncooperative pediatric patients. Included in the study were 160 children with a mean age of 6.7 +/- 2.6 years (1-14 years), 83 boys and 77 girls. All the patients had been referred for specialist treatment due to behavioral management problems. Treatment was performed in 250 sessions. All the children received an oral dose of 0.2 mg/kg body weight of midazolam. Acceptance of treatment was evaluated according to Rud & Kisling. Local anesthesia followed by restorative treatment and/or extractions constituted more than 90% of the performed treatments. Of the 250 sessions, 63% were performed with total acceptance and 30% with doubtful acceptance. In 7%, no treatment could be performed. No serious complications were registered during or after treatment. All the children were able to leave the clinic one hour after treatment. In conclusion, we consider oral administration of midazolam a safe form of premedication. The route of administration, the short waiting-time and half-life, in combination with a level of sedation that allows treatment to be performed, are the principal advantages of conscious sedation with orally administered midazolam.

Oral administration of yessotoxin stabilizes E-cadherin in mouse colon

International Nuclear Information System (INIS)

Callegari, Federica; Sosa, Silvio; Ferrari, Sara; Soranzo, Maria Rosa; Pierotti, Silvia; Yasumoto, Takeshi; Tubaro, Aurelia; Rossini, Gian Paolo

2006-01-01

YTX has been shown to disrupt the E-cadherin-catenin system in cultured epithelial cells, raising some concern that ingestion of seafood contaminated by YTX might favour tumour spreading and metastasis formation in vivo. In order to probe whether YTX might affect cadherin systems in vivo, we have set up a study involving repeated oral dosing of the toxin in mice (1 mg/kg/day, for 7 days) and analysis of E-cadherin and N-cadherin in tissue extracts obtained at the end of the dosing scheme, as well as 1 and 3 months after YTX administration. We found that the E-cadherin pools obtained from lung and kidney were not altered by YTX in any of our experimental conditions. Extracts from mouse colon contained intact E-cadherin and an E-cadherin fragment of about 90 kDa (ECRA 9 ), displaying a molecular alteration resembling that caused by YTX in cultured cells. We found that the relative proportion of ECRA 9 , as compared to intact E-cadherin, was higher in colon extracts from control mice than from YTX-treated animals, indicating that oral administration of YTX to mice stabilizes E-cadherin of mouse colon. No significant difference could be detected in samples prepared from colons obtained 30 or 90 days after termination of YTX treatment. Oral administration of YTX to mice did not lead to a significant increase in the fragments of E-cadherin detectable in serum, neither it altered the N-cadherin pool of mouse heart. Electron microscopy analysis showed no substantial ultrastructural differences between controls and YTX-treated mice. Our findings show that ingestion of food contaminated by YTX poses a low risk of disruption of the E-cadherin system in vivo

Bioavailibility of higher dose methotrexate comparing oral and subcutaneous route of administration in patients with rheumatoid arthritis

NARCIS (Netherlands)

Hoekstra, Monique; Hoekstra, M.; Haagsma, Cees; Neef, Cees; Proost, Johannes; van de Laar, Mart A F J; Knuif, Antonius

2004-01-01

OBJECTIVE: To determine the bioavailability of higher oral doses of methotrexate (MTX) in adult patients with rheumatoid arthritis (RA). METHODS: A pharmacokinetic analysis was performed in 15 patients with RA taking a stable dose of MTX (> or = 25 mg weekly). Separated by 2 weeks, a pharmacokinetic

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.

PHARMACOKINETICS OF DICLOFENAC SODIUM AND PAPAVERINE HYDROCHLORIDE AFTER ORAL ADMINISTRATION OF TABLETS TO RABBITS.

Science.gov (United States)

Kasperek, Regina; Zimmer, Łukasz; Jawień, Wojciech; Poleszak, Ewa

2015-01-01

Non-compartmental pharmacokinetic analysis of diclofenac sodium (DIC) and papaverine hydrochloride (PAP) after oral administration of composed tablets to rabbits was developed. HPLC method for determination of DIC and PAP in rabbit plasma was developed and validated. Chromatographic separation of DIC, PAP and the IS was achieved on a Zorbax SB C18 5-µm column (150 mm x 4.6 mm) using methanol-water (55:45, v/v) as mobile phase at a flow rate of 0.8 mL/min. Pharmacokinetic analysis showed that oral administration of a tablet composed of DIC and PAP do not change the pharmacokinetic parameters such as MRT, MAT, Cl and bioavailability of the active substances compared with single administration of DIC and PAP after single dose.

Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

Science.gov (United States)

Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

2018-01-20

Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted 5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

Halloysite nanotubes-induced Al accumulation and oxidative damage in liver of mice after 30-day repeated oral administration.

Science.gov (United States)

Wang, Xue; Gong, Jiachun; Gui, Zongxiang; Hu, Tingting; Xu, Xiaolong

2018-06-01

Halloysite (Al 2 Si 2 O 5 (OH) 4 ·nH 2 O) nanotubes (HNTs) are natural clay materials and widely applied in many fields due to their natural hollow tubular structures. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility, however the in vivo toxicity of HNTs remains unclear. The objective of this study was to assess the hepatic toxicity of the purified HNTs in mice via oral route. The purified HNTs were orally administered to mice at 5, 50, and 300 mg/kg body weight (BW) every day for 30 days. Oral administration of HNTs stimulated the growth of the mice at the low dose (5 mg/kg BW) with no liver toxicity, but inhibited the growth of the mice at the middle (50 mg/kg BW) and high (300 mg/kg BW) doses. In addition, oral administration of HNTs at the high dose caused Al accumulation in the liver but had no marked effect on the Si content in the organ. The Al accumulation caused significant oxidative stress in the liver, which induced hepatic dysfunction and histopathologic changes. These findings demonstrated that Al accumulation-induced oxidative stress played an important role in the oral HNTs-caused liver injury. © 2018 Wiley Periodicals, Inc.

Elimination of cetirizine 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

2016-10-01

Cetirizine is an antihistamine used in performance horses for the treatment of hypersensitivity reactions and as such a withdrawal time is necessary prior to competition. The objective of the current study was to describe the disposition and elimination of cetirizine following oral administration in order to provide additional serum concentration data upon which appropriate regulatory recommendations can be established. Nine exercised thoroughbred horses were administered 0.4 mg/kg of cetirizine orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum cetirizine concentrations were determined and selected pharmacokinetic parameters determined. The serum elimination half-life was 5.83 ± 0.841 h. Average serum cetirizine concentrations were still above the LOQ of the assay (0.05 ng/mL) at 48 h (final sample collected) postadministration of the final dose. © 2016 John Wiley & Sons Ltd.

The effects of oral and intramuscular administration and dose escalation of enrofloxacin on the selection of quinolone resistance among Salmonella and coliforms in pigs

DEFF Research Database (Denmark)

Wiuff, C.; Lykkesfeldt, J.; Svendsen, O.

2003-01-01

The effect of route of administration and dose of enrofloxacin (Baytril(R)) on the development of fluoroquinolone resistance in Salmonella and Escherichia coli in the intestinal tract of pigs was investigated. Healthy pigs at the age of 8-10 weeks were infected with a mixture of susceptible wild......-type (MICciprofloxacin = 0.03 mug/ml) and a mutant Salmonella typhimurium with reduced susceptibility to fluoroquinolones (MICciprofloxacin 0.5 mug/ml) (in the ratio 99: 1) and treated with 2.5 mg/kg bwt enrofloxacin by either intramuscular (i.m.) or oral (p.o.) administration at time points either 4 or 24 It after....... The Salmonella infection was cleared in all cases during the 2 weeks independent of frequency of resistance. The study showed that resistance is very easily selected by treatment with enrofloxacin at the recommended dose 2.5 mg/kg bwt, but also that the intensity of selection can be reduced by using...

In vivo analysis of supersaturation/precipitation/absorption behavior after oral administration of pioglitazone hydrochloride salt; determinant site of oral absorption.

Science.gov (United States)

Tanaka, Yusuke; Sugihara, Masahisa; Kawakami, Ayaka; Imai, So; Itou, Takafumi; Murase, Hirokazu; Saiki, Kazunori; Kasaoka, Satoshi; Yoshikawa, Hiroshi

2017-08-30

The purpose of this study was to evaluate in vivo supersaturation/precipitation/absorption behavior in the gastrointestinal (GI) tract based on the luminal concentration-time profiles after oral administration of pioglitazone (PG, a highly permeable lipophilic base) and its hydrochloride salt (PG-HCl) to rats. In the in vitro precipitation experiment in the classic closed system, while the supersaturation was stable in the simulated gastric condition, PG drastically precipitated in the simulated intestinal condition, particularly at a higher initial degree of supersaturation. Nonetheless, a drastic and moderate improvement in absorption was observed in vivo at a low and high dose of PG-HCl, respectively. Analysis based on the luminal concentration of PG after oral administration of PG-HCl at a low dose revealed that most of the dissolved PG emptied from the stomach was rapidly absorbed before its precipitation in the duodenum. At a high dose of PG-HCl, PG partly precipitated in the duodenum but was absorbed to some extent. Therefore, the extent of the absorption was mainly dependent on the duodenal precipitation behavior. Furthermore, a higher-than expected absorption after oral administration of PG-HCl from in vitro precipitation study may be due to the absorption process in the small intestine, which suppresses the precipitation by removal of the drug. This study successfully clarify the impact of the absorption process on the supersaturation/precipitation/absorption behavior and key absorption site for a salt formulation of a highly permeable lipophilic base based on the direct observation of in vivo luminal concentration. Our findings may be beneficial in developing an ideal physiologically based pharmacokinetic model and in vitro predictive dissolution tools and/or translating the in silico and in vitro data to the in vivo outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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.

[Oral loading dose of phenytoin in the treatment of serial seizures, prevention of seizure recurrence and rapid drug substitution].

Science.gov (United States)

Sokić, D; Janković, S M

1994-01-01

Over a period of nine months twenty-five epileptic patients were treated with the oral loading dose of phenytoin. The dose ranged from 12 to 23 mg/kg body weight during 1 to 12 hours. In 20 patients with serial seizures or intolerance to other antiepileptic drugs this treatment was effective. Seizures also stopped in 2 of 4 patients with serial partial motor seizures. These 2 patients required both higher loading dose and faster rate of administration than the other patients. A patient with epilepsia partialis continua failed to respond to the treatment. Patients that received phenytoin through the naso-gastric tube, in respect to oral administration, required higher doses to obtain therapeutic plasma levels of phenytoin. One patient had mild nausea, 3 mild dizziness, and 1 tinitus on the first day of the treatment. There was no correlation between a given dose and the achieved phenytoin plasma levels. In our opinion the therapy with oral loading dose of phenytoin is highly effective in the treatment of serial generalized seizures and rapid antiepileptic drug substitution, and partially effective in the prevention of partial motor seizures. It produces only mild and transient side-effects.

Brief oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients.

Science.gov (United States)

Mori, Takehiko; Yamazaki, Rie; Aisa, Yoshinobu; Nakazato, Tomonori; Kudo, Masumi; Yashima, Tomoko; Kondo, Sakiko; Ikeda, Yasuo; Okamoto, Shinichiro

2006-04-01

We previously reported the efficacy of oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis. The purpose of this study was to evaluate whether the further shortening of the duration of oral cryotherapy could minimize its side effects while sparing its efficacy. Seventeen consecutive recipients of allogeneic hematopoieic stem cell transplant conditioned with high-dose melphalan in combination with fludarabine alone or with fludarabine and additional radiation were enrolled in the study. The severity of stomatitis was graded according to the National Cancer Institute-Common Toxicity Criteria. Patients were kept on oral cryotherapy shortly before, during, and for additional 30 min after the completion of melphalan administration (60-min oral cryotherapy). Patients who were also enrolled in our previous study received the same type of oral cryotherapy but for additional 90 min after the completion of melphalan administration (120-min oral cryotherapy), and they served as controls. Only 2 (11.8%) of 17 patients receiving 60-min oral cryotherapy and 2 (11.1%) of 18 patients receiving 120-min oral cryotherapy developed grade 2 or 3 stomatitis, respectively. The difference between groups was not statistically significant (P = 0.677). The incidence of unpleasant symptoms such as chills and nausea during oral cryotherapy decreased significantly with 60-min oral cryotherapy, as compared with that associated with 120-min oral cryotherapy (P cryotherapy is as effective as 120-min oral cryotherapy at preventing high-dose melphalan-induced stomatitis, and shorter treatment might have contributed to relieve patient discomfort during oral cryotherapy.

Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats

Directory of Open Access Journals (Sweden)

Jia Choi

2018-01-01

Full Text Available Gelidium elegans extract (GEE is derived from a red alga from the Asia–Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

Supraspinally-administered agmatine attenuates the development of oral fentanyl self-administration

Science.gov (United States)

Wade, Carrie L.; Schuster, Daniel J.; Domingo, Kristine M.; Kitto, Kelley F.; Fairbanks, Carolyn A.

2009-01-01

The decarboxylation product of arginine, agmatine, has effectively reduced or prevented opioid-induced tolerance and dependence when given either systemically (intraperitoneally or subcutaneously) or centrally (intrathecally or intracerebroventricularly). Systemically administered agmatine also reduces the escalation phase of intravenous fentanyl self-administration in rats. The present study assessed whether centrally (intracerebroventricular, i.c.v.) delivered agmatine could prevent the development of fentanyl self-administration in mice. Mice were trained to respond under a fixed-ratio 1 (FR1) schedule for either fentanyl (0.7 μg/70 μl, p.o.) or food reinforcement. Agmatine (10 nmol/5 μl), injected i.c.v. 12-14h before the first session and every other evening (12-14h before session) for 2 weeks, completely attenuated oral fentanyl self-administration (but not food-maintained responding) compared to saline-injected controls. When agmatine was administered after fentanyl self-administration had been established (day 8) it had no attenuating effects on bar pressing. This dose of agmatine does not decrease locomotor activity as assessed by rotarod. The present findings significantly extend the previous observation that agmatine prevents opioid-maintained behavior to a chronic model of oral fentanyl self-administration as well as identifying a supraspinal site of action for agmatine inhibition of drug addiction. PMID:18495108

Pharmacokinetics of opicapone, a third-generation COMT inhibitor, after single and multiple oral administration: A comparative study in the rat

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Gonçalves, Daniela [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); Alves, Gilberto, E-mail: gilberto@fcsaude.ubi.pt [CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); CICS-UBI – Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã (Portugal); Fortuna, Ana [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); Soares-da-Silva, Patrício [Department of Research and Development, BIAL – Portela & Ca S.A., Av. da Siderurgia Nacional, 4745-457 S. Mamede do Coronado (Portugal); MedInUP – Center for Drug Discovery and Innovative Medicines, University Porto, Porto (Portugal); Falcão, Amílcar [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal)

2017-05-15

Opicapone is a novel potent, reversible and purely peripheral catechol-O-methyltransferase inhibitor that has been developed to be used as an adjunct to levodopa/aromatic L-amino acid decarboxylase inhibitor therapy for Parkinson's disease. Thus, this study aimed to compare the plasma pharmacokinetics of opicapone and its active metabolite (BIA 9-1079) after the administration of single and multiple oral doses to rats. Wistar rats (n = 8 per group) were orally treated with single (30, 60 or 90 mg/kg) or multiple (30 mg/kg once-daily for seven consecutive days) oral doses of opicapone. Blood samples were collected up to 24 h post-dosing through a cannula introduced in the tail vein of rats. After quantifying opicapone and BIA 9-1079 in plasma, a non-compartmental pharmacokinetic analysis was performed. Opicapone was quickly absorbed (time to reach the maximum plasma concentration ≤ 2 h) in both dosage regimens and the extent of systemic exposure to opicapone increased approximately in a dose-proportional manner after single-dosing within the studied dose range (30–90 mg/kg). Opicapone and BIA 9-1079 showed a relatively short plasma elimination half-life (1.58–4.50 h) and a small systemic accumulation after multiple-dosing. Hence, no pharmacokinetic concerns are expected when opicapone is administered with a once-daily dosing regimen. - Highlights: • Opicapone is relatively rapid absorbed after oral administration to rats. • Systemic exposure to opicapone increases approximately in a dose-proportional manner. • Opicapone and BIA 9-1079 show a small systemic accumulation after multiple-dosing.

Safety of fluralaner oral solution, a novel systemic antiparasitic treatment for chickens, in laying hens after oral administration via drinking water.

Science.gov (United States)

Prohaczik, Angella; Menge, Monika; Huyghe, Bruno; Flochlay-Sigognault, Annie; Traon, Gaëlle Le

2017-08-08

Poultry mites are the most significant pest affecting production systems in the egg-laying industry. Fluralaner is a novel systemic insecticide and acaricide that is effective against poultry mites (Dermanyssus gallinae, Ornithonyssus sylviarum) in chickens after oral administration. This study investigated the safety of oral administration of a 1% solution of fluralaner in drinking water to laying hens at the recommended treatment dose and at multiples of this dose. One hundred-twenty healthy 28-week-old laying hens, weighing 1.4-2.1 kg at first administration, were included in the study, and allocated to 4 treatment groups of 30 hens each receiving daily doses of 0, 0.5, 1.5 and 2.5 mg fluralaner/kg body weight, equivalent to 0, 1, 3, and 5 times the recommended dose of fluralaner. The product was administered via drinking water on a total of six occasions, as 3-day treatment periods twice with an interval of 4 days with no treatment (treatment on days 1, 2, 3 and 8, 9, 10), representing 3 times the recommended number of administrations. Hens supplied with non-medicated drinking water served as controls. During the study, all hens were clinically observed, and their health was carefully monitored including body weight, food and water consumption, hematology, clinical chemistry, and withdrawal reflex test. Eggs laid over the study were evaluated for main characteristics (e.g. weight, shape, strength, shell thickness and soundness, albumen height, yolk color, Haugh unit and presence of blood and/or meat spots). Following euthanasia of the hens at the end of the second treatment period (day 11) or 18 days later (day 29), complete gross post-mortem examination, including organ weight determination, and histopathological examination of multiple tissues were conducted. There were no clinical findings related to fluralaner treatment. Statistically significant differences between the treated groups and the control group were observed for some clinical pathology

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.

Comparison of oral versus rectal administration of acetaminophen with codeine in postoperative pediatric adenotonsillectomy patients.

Science.gov (United States)

Owczarzak, Vicki; Haddad, Joseph

2006-08-01

To examine whether acetaminophen with codeine administered per rectum is an effective alternative for pain control compared with oral administration after an adenotonsillectomy. A prospective, randomized control study. Seventy-five children aged 1 to 5 were recruited for this study. Each child was assigned randomly to receive either rectal or oral postoperative pain medication. A journal with eight questions was kept for 10 days after the operation, and an overall survey of five questions was filled out at the first postoperative visit. Postoperative pain was adequately controlled in those patients receiving suppositories when compared with those patients receiving oral pain medication. Adverse effects and total number of doses given per day were similar. Parents found the suppositories easy to administer, and more parents would switch or consider switching from oral pain medication to suppositories if given the choice. The suppositories achieved equivalent pain control as oral medication with few side effects and good tolerance. Furthermore, many parents preferred the suppositories to oral medication in maintaining postoperative pain control because of ease of administration. If given the choice for future surgeries, many parents would switch or consider switching from oral pain medication to suppositories.

Mouse single oral dose toxicity test of bupleuri radix aqueous extracts.

Science.gov (United States)

Kim, Kyung-Hu; Gam, Cheol-Ou; Choi, Seong-Hun; Ku, Sae-Kwang

2012-03-01

The aim of this study was to evaluate the single oral dose toxicity of Bupleuri Radix (BR) aqueous extracts, it has been traditionally used as anti-inflammatory agent, in male and female mice. BR extracts (yield = 16.52%) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 14 principal organs were examined. As the results, no BR extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs were detected up to 2,000 mg/kg in both female and male mice, except for soft feces and related body weight decrease detected in male mice treated with 2,000 mg/kg. Therefore, LD50 (50% lethal dose) and approximate LD of BR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg, respectively. Although it was also observed that the possibilities of digestive disorders, like soft feces when administered over 2,000 mg/kg of BR extracts in the present study, these possibilities of digestive disorders can be disregard in clinical use because they are transient in the highest dosages male only.

Formulation design of oral pediatric Acetazolamide suspension: dose uniformity and physico-chemical stability study.

Science.gov (United States)

Santoveña, Ana; Suárez-González, Javier; Martín-Rodríguez, Cristina; Fariña, José B

2017-03-01

The formulation of an active pharmaceutical ingredient (API) as oral solution or suspension in pediatrics is a habitual practice, due to the non-existence of many commercialized medicines in pediatric doses. It is also the simplest way to prepare and administer them to this vulnerable population. The design of a formulation that assures the dose and the system stability depends on the physico-chemical properties of the API. In this study, we formulate a class IV API, Acetazolamide (AZM) as suspension for oral administration to pediatric population. The suspension must comply attributes of quality, safety and efficacy for this route of administration. We use simple compounding procedures, as well as fewer pure excipients, as recommended for children. Mass and uniformity content assays and physical and chemical stability studies were performed. To quantify the API an UPLC method was used. We verified the physico-chemical stability of the suspensions and that they passed the mass test of the European Pharmacopeia (EP), but not the dose uniformity test. This reveals that AZM must be formulated as liquid forms with a more complex system of excipients (not usually indicated in pediatrics), or otherwise solid forms capable of assuring uniformity of mass and dose for every dosage unit.

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).

Intravenous voriconazole after toxic oral administration

NARCIS (Netherlands)

Alffenaar, J.W.C.; Van Assen, S.; De Monchy, J.G.R.; Uges, D.R.A.; Kosterink, J.G.W.; Van Der Werf, T.S.

In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate

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...

Effect of combined oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models.

Science.gov (United States)

Rock, Erin M; Connolly, Cassidy; Limebeer, Cheryl L; Parker, Linda A

2016-09-01

The purpose of this study was to evaluate the potential of oral combined cannabis constituents to reduce nausea. The objective of this study was to determine the effect of combining subthreshold oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models of conditioned gaping. The potential of intragastric (i.g.) administration of THC, CBDA, or combined doses, to interfere with acute nausea-induced conditioned gaping (acute nausea) or the expression of contextually elicited conditioned gaping (anticipatory nausea), was evaluated. For acute nausea, i.g. administration of subthreshold doses of THC (0.5 and 1 mg/kg) or CBDA (0.5 and 1 μg/kg) significantly suppressed acute nausea-induced gaping, whereas higher individual doses of both THC and CBDA were maximally effective. Combined i.g. administration of higher doses of THC and CBDA (2.5 mg/kg THC-2.5 μg/kg CBDA; 10 mg/kg THC-10 μg/kg CBDA; 20 mg/kg THC-20 μg/kg CBDA) also enhanced positive hedonic reactions elicited by saccharin solution during conditioning. For anticipatory nausea, combined subthreshold i.g. doses of THC (0.1 mg/kg) and CBDA (0.1 μg/kg) suppressed contextually elicited conditioned gaping. When administered i.g., THC was effective on its own at doses ranging from 1 to 10 mg/kg, but CBDA was only effective at 10 μg/kg. THC alone was equally effective by intraperitoneal (i.p.) and i.g. administration, whereas CBDA alone was more effective by i.p. administration (Rock et al. in Psychopharmacol (Berl) 232:4445-4454, 2015) than by i.g. administration. Oral administration of subthreshold doses of THC and CBDA may be an effective new treatment for acute nausea and anticipatory nausea and appetite enhancement in chemotherapy patients.

Pharmacokinetics of /sup 3/H-pipethiaden after single oral and intravenous administration in rats

Energy Technology Data Exchange (ETDEWEB)

Lapka, R.; Franc, Z.; Smolik, S.

1985-01-01

Tritium labelled anti-migraine drug 4-(1-methyl-4-piperidyliden)-4,9-duhydrothieno(2,3-c)-2-benzothiepine (pipethiaden) was prepared. After oral and intravenous administration to rats not only the courses of total radioactivity in plasma and various organs were determined, but by means of TLC-radiometry also the levels of pipethiaden itself. After the oral dose 1.35 mg/kg the plasma levels of pipethiaden did not exceed 3.5 ng/ml. Some pharmacokinetic parameters (e.g. t/sub 1/2/el-4h) were calculated by compartmental analysis of plasma levels.

Protective effect of oral administration of transgenic tobacco seeds against verocytotoxic Escherichia coli strain in piglets.

Science.gov (United States)

Rossi, Luciana; Dell'Orto, Vittorio; Vagni, Simona; Sala, Vittorio; Reggi, Serena; Baldi, Antonella

2014-03-01

The use of transgenic plants as delivery system for antigenic proteins is attractive for its simplicity and increases likelihood for local immune response at sites of infection. The aim of this study was to evaluate the protective effect of oral administration of tobacco seeds, expressing the FedA, the major protein of the F18 adhesive fimbriae, and B subunit of verocytotoxin, against verocytotoxin-producing E. coli (VTEC) strain in piglets. Forty-three early weaned piglets, were randomly divided into 4 experimental groups: 3 test groups and a control. Treatment groups orally received a bolus, with different dose of tobacco seeds on 0, 1, 2, 14 days post primary administration. After challenge, with 1*10(10) CFU of O138 Escherichia coli strain, piglets showed clinical scores significantly higher in the control group compared to orally immunized groups (P administration of recombinant tobacco seeds expressing antigenic proteins against VTEC strains can induce a protective effect against challenger strain in piglets.

Absorption, distribution, metabolism and excretion of selenium following oral administration of elemental selenium nanoparticles or selenite in rats

DEFF Research Database (Denmark)

Löschner, Katrin; Hadrup, Niels; Hansen, Marianne

2014-01-01

A suspension of nanoparticles of BSA-stabilized red amorphous elemental selenium (Se) or an aqueous solution of sodium selenite was repeatedly administered by oral gavage for 28 days at 0.05 mg/kg bw/day (low dose) or at 0.5 mg/kg bw/day (high dose) as Se to female rats. Prior to administration...

Toxicokinetics of the ciguatoxin P-CTX-1 in rats after intraperitoneal or oral administration.

Science.gov (United States)

Bottein, Marie-Yasmine Dechraoui; Wang, Zhihong; Ramsdell, John S

2011-06-18

Ciguatoxins are voltage-gated selective algal toxins responsible for ciguatera fish poisoning. In this study we evaluate the toxicokinetics of one of the most common ciguatoxins found in the Pacific, the P-CTX-1, in rat after an oral or intraperitoneal (ip) dose of 0.26 μg/kg body weight. We report levels of ciguatoxin activity assessed over time in blood, urine and feces, and at 4 days in liver, muscle and brain, using the functional in vitro N2A cytotoxicity assay. Following exposure, the ciguatoxin activity exhibited a rapid systemic absorption that was followed by a bi-exponential decline, and data best fit a two-compartment model analysis. Maximum blood concentrations were reached at 1.97 and 0.43 h after the oral and ip dose, respectively. Ciguatoxin elimination from blood was slow with terminal half lives (t(½)β) estimated at 82 h for oral and 112 h for ip dosing. Ciguatoxin activity remained in liver, muscle and brain 96 h after ip and oral administration. While smaller amounts appeared in the urine, the main excretion route was feces, with peak rates reaching > 10 pg P-CTX-1 equivalents/h in both routes of administration. Assay guided fractionation showed the presence in the feces and liver of peaks of activity corresponding to the P-CTX-1 and to other less polar metabolites. In conclusion, biologically active ciguatoxins are detectable in blood, liver, muscle and brain, and continued to be excreted in urine and feces 4 days following exposure. Blood, as well as urine and feces may be useful matrices for low-invasive testing methods for ciguatera clinical cases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

High Dose Oral Calcium Treatment in Patients with Vitamin D-dependent Rickets Type II

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R Vakili

2017-02-01

Full Text Available BACKGROUND AND OBJECTIVE: Vitamin D-dependent rickets type II (VDDR2 is a rare genetic disorder caused by mutations in vitamin D receptor (VDR and leads to resistance to biological effects of calcitriol. Based on the type of mutation, this disease is resistant to calcitriol even at high doses of calcitriol and successful treatment of these patients requires hypocalcemic modification through administration of high doses of calcium and bypassing the intestinal defect in VDR signaling. In addition to the need for frequent hospitalization and high costs, intravenous administration of calcium is associated with complications and problems such as arrhythmia and sepsis, venous catheter infection and hypercalciuria. This study aims to report the positive treatment effects of high doses of oral calcium in 4 patients with vitamin D-dependent rickets type II. CASE REPORT: In this study, 4 patients with vitamin D-dependent rickets type II, diagnosed based on clinical and biochemical symptoms of rickets with alopecia, underwent therapy using high doses of oral calcium (300 mg/kg/day in pediatric endocrinology and metabolism center of Imam Reza hospital. After a short period, increased growth rate in height, strength and elasticity of muscles was observed in addition to biochemical improvements without serious side effects and even one patient started walking independently within the first week of therapy for the first time. Patients were regularly followed up in terms of height and weight, growth rate and biochemical factors including calcium, phosphorus and alkaline phosphatase every 3 months for one year. CONCLUSION: Regardless of the type of mutation in vitamin D receptor, it is suggested that a 3-6 months trial of high dose oral calcium be started in each patient with vitamin D-dependent rickets type II, particularly for patients whose disease was diagnosed at lower ages.

PHARMACOKINETICS OF SINGLE-DOSE ORALLY ADMINISTERED CIPROFLOXACIN IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

Science.gov (United States)

Barbosa, Lorraine; Johnson, Shawn P; Papich, Mark G; Gulland, Frances

2015-06-01

Ciprofloxacin is commonly selected for clinical use due to its broad-spectrum efficacy and is a frequently administered antibiotic at The Marine Mammal Center, a marine mammal rehabilitation facility. Ciprofloxacin is used for treatment of California sea lions ( Zalophus californianus ) suffering from a variety of bacterial infections at doses extrapolated from other mammalian species. However, as oral absorption is variable both within and across species, a more accurate determination of appropriate dosage is needed to ensure effective treatment and avoid emergence of drug-resistant bacterial strains. A pharmacokinetic study was performed to assess plasma concentrations of ciprofloxacin in California sea lions after a single oral dose. Twenty healthy California sea lions received a single 10-mg/kg oral dose of ciprofloxacin administered in a herring fish. Blood was then collected at two of the following times from each individual: 0.5, 0.75, 1, 2, 4, 8, 10, 12, 18, and 24 hr postingestion. Plasma ciprofloxacin concentration was assessed via high-performance liquid chromatography. A population pharmacokinetics model demonstrated that an oral ciprofloxacin dose of 10 mg/kg achieved an area under the concentration vs. time curve of 6.01 μg hr/ml. Absorption was rapid, with ciprofloxacin detectable in plasma 0.54 hr after drug administration; absorption half-life was 0.09 hr. A maximum plasma concentration of 1.21 μg/ml was observed at 1.01 hr, with an elimination half-life of 3.09 hr. Ciprofloxacin administered orally at 10 mg/kg produced therapeutic antibacterial exposure for only some of the most susceptible bacterial organisms commonly isolated from California sea lions.

Oral iron administration in suckling piglets – a review

Directory of Open Access Journals (Sweden)

Martin Svoboda

2018-01-01

Full Text Available Iron deficiency is presently a serious problem in suckling piglets on pig farms. The most often used method of anaemia prevention in piglets is parenteral administration of iron dextran. Oral iron represents an alternative to this method. The goal of this article is to review current knowledge on oral iron administration in suckling piglets. The substances that can be used for this purpose include iron dextran, iron salts, iron chelates, carbonyl iron, an iron polymaltose complex and iron microparticles. The different methods of oral iron administration in piglets are discussed.

A 5-month toxicity study of the ethanol extract of the leaves of Heliotropium indicum in Sprague Dawley rats after oral administration.

Science.gov (United States)

Owolabi, M A; Oribayo, O O; Ukpo, G E; Mbaka, G O; Akindehin, O E

2015-01-01

Heliotropium indicum Linn. (Boraginaceae) is used in Nigerian traditional medicine to treat tuberculosis with treatment lasting for 3 months; however, information on its toxicity is scarce. This study investigated the safety of the leaves of Heliotropium indicum after a 5 month oral administration. The leaves of H. indicum were dried; extracted in 70% ethanol and concentrated to dryness. Swiss mice were administered orally with single doses of the extract (0.5 to 12.0 g/kg b.wt /day); mortality was examined for up to 14 days. In another study, the plant material (0.5 to 2.0 g/kg b.wt /day) were administered daily by oral gavage to Sprague Dawley rats. Body weight was monitored weekly, hematological, biochemical and organ parameters were determined at the end of the 1st, 2nd and 5th months of extract administration. The oral administration of the ethanol extract of H. indicum caused dose-dependent mortality. The LD50 was 9.78 g/kg b.wt for the Swiss mice; no harmful effect was observed on the liver and kidney except the testes which exhibited considerable inflammatory changes at the highest dose of 2.0 g/kg b.wt./day after the 5th month treatment. No significant difference (P>0.05) was shown in the enzyme study, marginal increase occurred in some haematological parameters. The increase in body weight of the treated rats after its initial reduction was consistent and significantly different (P<0.05) from their initial body weight. Prolonged administration of the crude leaf extract of H. indicum is considered to be safe and nontoxic at the doses studied. However, there is a probability of a negative effect on the testes at a higher dose of the extract.

Vaxchora: A Single-Dose Oral Cholera Vaccine.

Science.gov (United States)

Cabrera, Adriana; Lepage, Jayne E; Sullivan, Karyn M; Seed, Sheila M

2017-07-01

To review trials evaluating the efficacy and safety of Vaxchora, a reformulated, single-dose, oral, lyophilized Vibrio cholerae CVD 103-HgR vaccine for the prevention of travel-related cholera caused by V cholerae serogroup O1. A literature search was conducted using MEDLINE (1946 to January week 3, 2017) and EMBASE (1996 to 2017 week 3). Keywords included oral cholera vaccine, single-dose, Vaxchora, and CVD 103-HgR. Limits included human, clinical trials published in English since 2010. ClinicalTrials.gov was used as a source for unpublished data. Additional data sources were obtained through bibliographic review of selected articles. Studies that addressed the safety and efficacy of Vaxchora, the reformulated, single-dose oral CVD 103-HgR cholera vaccine, were selected for analysis. Approval of Vaxchora, was based on efficacy of the vaccine in human trials demonstrating 90.3% protection among those challenged with V cholerae 10 days after vaccination and in immunogenicity studies with 90% systemic vibriocidal antibody conversion at 6 months after a single-dose of vaccine. Tolerability was acceptable, with the most common adverse effects reported to be fatigue, headache, and abdominal pain. Vaxchora is the only FDA-approved, single-dose oral vaccine for the prevention of cholera caused by V cholerae serogroup O1 in adult travelers from the United States going to cholera-affected areas. Safety and efficacy has not been established in children, immunocompromised persons, and pregnant or breastfeeding women or those living in cholera-endemic areas.

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

A novel, ecologically relevant, highly preferred, and non-invasive means of oral substance administration for rodents.

Science.gov (United States)

Sobolewski, Marissa; Allen, Joshua L; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A

2016-01-01

Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if they share biological targets. Consequently, it should be preferable to develop alternative methods without these potential confounds. The aim of this study was to determine the suitability of mealworms as an alternative treat-based method to deliver xenobiotics via the orogastric route. Accurate oral administration is contingent on motivation and preference; mice reliably preferred mealworms over wafer cookie treats. Further, ingestion of wafer cookies significantly increased mouse blood glucose levels, whereas unaltered mealworms produced no such change. Mealworms functioned effectively to orally administer glucose, as glucose-spiked mealworms produced a rise in blood glucose equivalent to the ingestion of the wafer cookie. Mealworms did not interfere with the physiological function of orally administered d-amphetamine, as both mealworm and oral gavage administered d-amphetamine showed similar alterations in locomotor behavior (mice did not fully consume d-amphetamine-dosed cookies and thus could not be compared). Collectively, the findings indicate that mealworms are a preferred and readily consumed treat, which importantly mimics environmental-relevant nutritional intake, and mealworms per se do not alter glucose metabolic pathways. Additionally, mealworms accurately delivered xenobiotics into blood circulation and did not interfere with the physiological function of administered xenobiotics. Thus mealworm-based oral administration may be a preferable and accurate route of

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.

Comparação da eficácia de doses iguais de acetaminofeno retal e oral em crianças Comparison of antipyretic effectiveness of equal doses of rectal and oral acetaminophen in children

Directory of Open Access Journals (Sweden)

Sedigha Akhavan Karbasi

2010-06-01

Full Text Available OBJETIVO: Comparar uma dose de acetaminofeno oral e retal e avaliar a aceitabilidade do acetaminofeno retal, uma vez que o acetaminofeno oral e retal é amplamente usado como agente antipirético em crianças com febre e a eficiência comparativa dessas duas preparações não está bem estabelecida. MÉTODOS: Neste estudo prospectivo de grupos paralelos, foram incluídas 60 crianças admitidas na emergência ou clínica ambulatorial pediátrica em um hospital terciário, com idade entre 6 meses e 6 anos e com temperatura retal acima de 39 °C. Os pacientes foram distribuídos aleatoriamente em dois grupos de mesmo tamanho. O grupo 1 recebeu 15 mg/kg de acetaminofeno retal, e o grupo 2 recebeu a mesma dose oralmente. A temperatura foi registrada no tempo zero e 1 e 3 horas após administração da droga. RESULTADOS: No primeiro grupo, a redução média de temperatura, 1 e 3 horas após administração do acetaminofeno, foi de 1,07±0,16 (p 0,05. CONCLUSÃO: As preparações oral e retal de acetaminofeno têm eficácia antipirética equivalente em crianças. A via retal mostrou ser tão aceitável quanto a oral entre os pais.OBJECTIVE: To compare a dose of oral and rectal acetaminophen and to evaluate acceptability of rectal acetaminophen, since oral and rectal acetaminophen is widely used as an antipyretic agent in febrile children and the comparative effectiveness of these two preparations is not well established. METHODS: In this prospective parallel group designed study, 60 children who presented to the emergency department or outpatient pediatric clinic at a tertiary hospital and aged from 6 months to 6 years with rectal temperature over 39 °C were enrolled. Patients were randomly assigned to two equal-sized groups. Group 1 received 15 mg/kg acetaminophen rectally and group 2 received the same dose orally. Temperature was recorded at baseline and 1 and 3 hours after drug administration. RESULTS: In the first group, mean decrease in

Oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients.

Science.gov (United States)

Aisa, Yoshinobu; Mori, Takehiko; Kudo, Masumi; Yashima, Tomoko; Kondo, Sakiko; Yokoyama, Akihiro; Ikeda, Yasuo; Okamoto, Shinichiro

2005-04-01

The purpose of this study was to evaluate the efficacy of oral cryotherapy to prevent high-dose melphalan-induced stomatitis. Eighteen consecutive recipients of allogeneic hematopoietic stem cell transplant conditioned with high-dose melphalan (140 mg/m2) in combination with fludarabine alone or with fludarabine and additional chemotherapy or radiation were enrolled. The severity of stomatitis was graded according to the National Cancer Institute Common Toxicity Criteria. Patients were kept on oral cryotherapy using ice chips and ice-cold water shortly before, during, and for additional 90 min after completion of melphalan administration. Only two of 18 patients (11.1%) developed grade 2 or 3 stomatitis while six of seven patients in the historical control developed it (85.7%; P=0.001). These results suggested that oral cryotherapy could effectively prevent stomatitis caused by high-dose melphalan, and we recommend that it should be incorporated into the conditioning regimen with high-dose melphalan.

Nickel Excretion in Urine after Oral Administration

DEFF Research Database (Denmark)

Menne, T.; Mikkelsen, H. I.; Solgaard, Per Bent

1978-01-01

In recent years the importance of internal exposure to nickel in patients with recurrent hand eczema and nickel allergy has become evident. The present study was performed in order to investigate the value of urinary nickel determinations as an index of oral nickel intake. After oral administration...

Suspected adverse reactions to oral administration of a praziquantel-pyrantel combination in captive cheetahs (Acinonyx jubatus).

Science.gov (United States)

Whitehouse-Tedd, Katherine M; Smith, Liesl; Budd, Jane A; Lloyd, Christopher G

2017-11-15

OBJECTIVE To characterize adverse reactions to oral administration of a combination of praziquantel and pyrantel embonate or pyrantel pamoate, with or without oxantel embonate, in captive cheetahs (Acinonyx jubatus). DESIGN Retrospective case series and case-control study. ANIMALS 16 captive cheetahs with signs of adverse reaction to oral administration of praziquantel and pyrantel, with or without oxantel embonate (affected group), and 27 cheetahs without such reactions (unaffected group), all from 3 independent facilities. PROCEDURES Medical records and postmortem findings for affected cheetahs were reviewed and compared with those of unaffected animals. Anthelmintic doses administered, age, and sex of cheetahs were compared between groups. RESULTS 3 reactions in affected cheetahs were fatal, whereas the remainder ranged from mild to severe. Postmortem examination failed to reveal any disease processes or conditions to explain the deaths. No differences in anthelmintic dose were identified between affected and unaffected cheetahs for all facilities combined, and no correlation existed between dose and reaction severity. No association with sex was detected, but affected cheetahs were significantly younger than unaffected cheetahs. This difference was not significant after controlling for facility. CONCLUSIONS AND CLINICAL RELEVANCE Cheetahs were concluded to have had an adverse reaction to the praziquantel-pyrantel combination because of temporal proximity of onset of clinical signs to dose administration, similarity of signs to those reported for toxicosis in other species for these drugs, and a lack of other disease process or environmental explanatory factors. A highly cautious approach to the use of this drug combination is recommended for cheetahs.

Pharmacokinetics of posaconazole in koalas (Phascolarctos cinereus) after intravenous and oral administration.

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Gharibi, S; Kimble, B; Vogelnest, L; Barnes, J; Stadler, C K; Govendir, M

2017-12-01

The pharmacokinetic profile of posaconazole in clinically normal koalas (n = 8) was investigated. Single doses of posaconazole were administered intravenously (i.v.; 3 mg/kg; n = 2) or orally (p.o.; 6 mg/kg; n = 6) with serial plasma samples collected over 24 and 36 hr, respectively. Plasma concentrations of posaconazole were quantified by validated high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis of data was performed. Following i.v. administration, estimates of the median (range) of plasma clearance (CL) and steady-state volume of distribution (V ss ) were 0.15 (0.13-0.18) L hr -1  kg -1 and 1.23 (0.93-1.53) L/kg, respectively. The median (range) elimination half-life (t 1/2 ) after i.v. and p.o. administration was 7.90 (7.62-8.18) and 12.79 (11.22-16.24) hr, respectively. Oral bioavailability varied from 0.43 to 0.99 (median: 0.66). Following oral administration, maximum plasma concentration (C max ; median: 0.72, range: 0.55-0.93 μg/ml) was achieved in 8 (range 6-12) hr. The in vitro plasma protein binding of posaconazole incubated at 37°C was 99.25 ± 0.29%. Consideration of posaconazole pharmacokinetic/pharmacodynamic (PK/PD) targets for some yeasts such as disseminated candidiasis suggests that posaconazole could be an efficacious treatment for cryptococcosis in koalas. © 2017 John Wiley & Sons Ltd.

Oral metformin-ascorbic acid co-administration ameliorates alcohol-induced hepatotoxicity in rats.

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Adeneye, A A; Benebo, A S

2007-01-01

Alcoholic liver disease remains a major cause of liver failure worldwide with no available curative or prophylactic therapy as at present. High dose metformin is reported to ameliorate liver injuries in both human and animal models of acute and chronic alcoholic liver injuries. The aim of the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure. In the present study, ameliorating effect of 200 mg/ kg/day of ascorbic acid (Asc), 500 mg/kg/day of metformin (Met) and their co-administration (Met-Asc) were investigated in 5 groups of 50% ethanol-treated male Wistar rats for 2 weeks of the experiment. The body weight of each rat was taken on days 1, 7, and 14 of the experiment, respectively. On day 15, fasted blood samples for plasma lipids and liver enzyme markers were collected via cardiac puncture from the rats under diethyl ether anaesthesia. Results showed that administration of graded oral doses of 50% ethanol for 14 days significantly (pcholesterol (PTC), high density lipoprotein (HDL-c), and low density lipoprotein (LDL-c). However, these elevations were significantly (pascorbic acid co-administration protected the liver against the deleterious effects of chronic high dose alcohol and the hepatoprotective effect of Met-Asc appeared to be due mainly to the metformin molecule of the drug combination. However, further studies would be required to evaluate the mechanisms underlying the observed effects.

Oral pulsed high-dose dexamethasone for myositis

NARCIS (Netherlands)

van der Meulen, M. F.; Hoogendijk, J. E.; Wokke, J. H.; de Visser, M.

2000-01-01

To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Six patients responded. Side effects

Interaction of titanium dioxide nanoparticles with glucose on young rats after oral administration.

Science.gov (United States)

Chen, Zhangjian; Wang, Yun; Zhuo, Lin; Chen, Shi; Zhao, Lin; Chen, Tian; Li, Yang; Zhang, Wenxiao; Gao, Xin; Li, Ping; Wang, Haifang; Jia, Guang

2015-10-01

Titanium dioxide nanoparticles (TiO2 NPs) have a broad application prospect in replace with TiO2 used as a food additive, especially used in sweets. Understanding the interaction of TiO2 NPs with sugar is meaningful for health promotion. We used a young animal model to study the toxicological effect of orally administrated TiO2 NPs at doses of 0, 2, 10 and 50 mg/kg per day with or without daily consumption of 1.8 g/kg glucose for 30 days and 90 days. The results showed that oral exposure to TiO2 NPs and TiO2 NPs+glucose both induced liver, kidney, and heart injuries as well as changes in the count of white and red blood cells in a dose, time and gender-dependent manner. The toxicological interactions between orally-administrated TiO2 NPs and glucose were evident, but differed among target organs. These results suggest that it is necessary to limit dietary co-exposure to TiO2 NPs and sugar. Nanotechnology has gained entrance in the food industry, with the presence of nanoparticles now in many food items. Despite this increasing trend, the potential toxic effects of these nanoparticles to human remain unknown. In this article, the authors studied titanium dioxide nanoparticles (TiO2 NPs), which are commonly used as food additive, together with glucose. The findings of possible adverse effects on liver, kidney, and heart might point to a rethink of using glucose and TiO2 NPs combination. Copyright © 2015 Elsevier Inc. All rights reserved.

The pharmacokinetics of L-tryptophan following its intravenous and oral administration.

OpenAIRE

Green, A R; Aronson, J K; Cowen, P J

1985-01-01

The pharmacokinetics of L-tryptophan (5 g and 7.5 g) have been studied after its intravenous administration to healthy subjects and the results compared with those obtained after oral administration (0.7 g-3.5 g). In order to do this, we have re-analysed previously published data relating to oral administration. The data obtained following the oral administration of L-tryptophan suggest that the total body clearance and apparent volume of distribution are saturable. The pharmacokinetics of tr...

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

Hidratación oral continua o a dosis fraccionadas en niños deshidratados por diarrea aguda Oral rehydration in continuous administration or in fractionated doses in dehydrated children with acute diarrhea

Directory of Open Access Journals (Sweden)

Felipe Mota-Hernández

2002-01-01

Full Text Available Objetivo. Evaluar la seguridad y efectividad de dos técnicas de hidratación oral. Material y métodos. Ensayo clínico aleatorio, hecho en el Servicio de Hidratación Oral del Hospital Infantil de México, Federico Gómez, entre septiembre de 1998 y junio de 1999. Cuarenta pacientes deshidratados por diarrea aguda, menores de cinco años, recibieron suero oral ad libitum (grupo AL y otros cuarenta lo recibieron en dosis fraccionada (grupo DF. Las características clínicas fueron similares en ambos grupos. Los resultados se presentan como promedio y desviación estándar o mediana, según la distribución de frecuencias simples y relativas. Resultados. El promedio de gasto fecal en el grupo AL fue 11.0±7.5 g/kg/h y en el grupo DF 7.1±7.4 (p=0.03. La ingesta de suero, el tiempo de hidratación y la diuresis promedio, fueron similares entre ambos grupos (p>0.05. Seis pacientes del grupo AL y cinco del DF tuvieron gasto fecal alto (>10 g/kg/hora, mejorando con la administración de atole de arroz. Un paciente del grupo AL y dos pacientes del DF tuvieron vómitos persistentes, mejorando con gastroclisis. Ningún paciente requirió rehidratación intravenosa. Conclusiones. Estos resultados sugieren que la administración de suero oral ad libitum, bajo supervisión, es tan segura y efectiva como la técnica de dosis fraccionada para el tratamiento de niños deshidratados por diarrea aguda.Objective. To evaluate the safety and effectiveness of two oral rehydration techniques. Material and Methods. A randomized clinical trial was conducted at the oral rehydration unit of Hospital Infantil de Mexico "Federico Gomez", between September 1998 and June 1999. Forty patients five-year old and younger children, dehydrated due to acute diarrhea, were given oral rehydration solution (ORS ad libitum (AL group; another forty patients received ORS in fractionated doses (FD group. Clinical characteristics were similar in both groups. Results are presented as

Fenproporex and amphetamine pharmacokinetics in oral fluid after controlled oral administration of fenproporex.

Science.gov (United States)

Comiran, Eloisa; Souza, Daniele Zago; Boehl, Paula Otero; Cássia Mariotti, Kristiane de; Pechansky, Flavio; Duarte, Paulina do Carmo Arruda Vieira; De Boni, Raquel Brandini; Fröehlich, Pedro Eduardo; Limberger, Renata Pereira

2012-10-01

Fenproporex hydrochloride (FEN) is an anorectic drug used in the treatment of obesity, and its major metabolite is amphetamine (AMP), another central nervous system stimulant. The concentration versus time profile of FEN and its metabolite AMP has been described in classic biological matrices such as plasma and urine; however, there are no reports of such data in oral fluid. The aim of this study is to describe the pharmacokinetics of FEN and AMP in oral fluid after intake of FEN. Twenty-five milligrams of FEN (1 capsule of Desobesi-m) was orally administered to 6 male volunteers, and oral fluid samples were collected with a Quantisal device during 24.00 hours after drug ingestion. These samples were submitted to solid-phase microextraction before analysis by gas chromatography-mass spectrometry in the selected-ion-monitoring mode, using deuterium-labeled AMP as internal standard. After FEN administration, both analytes could be detected in oral fluid of all volunteers with an initial detection time varying from 0.50 to 1.00 hour. FEN peak concentrations occurred between 1.00 and 1.50 hours after administration and were between 70.7 and 227.5 μg/L. For AMP, peak concentration occurred between 1.50 and 4.00 hours, reaching 33.0-150.9 μg/L. The authors observed that oral administration of FEN resulted in significant amounts of FEN and AMP in oral fluid, showing that oral fluid could be a biological matrix suitable for pharmacokinetic studies for both analytes. Using a compartmental approach, FEN data were best fitted by 1-compartment model with first-order input and output, whereas AMP followed a 2-compartment model with first-order input and output.

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

Influence of Vehicles Used for Oral Dosing of Test Molecules on the Progression of Mycobacterium tuberculosis Infection in Mice

OpenAIRE

Singh, Shubhra; Dwivedi, Richa; Chaturvedi, Vinita

2014-01-01

Preclinical evaluation of drug-like molecules requires their oral administration to experimental animals using suitable vehicles. We studied the effect of oral dosing with corn oil, carboxymethyl cellulose, dimethyl sulfoxide, and polysorbate-80 on the progression of Mycobacterium tuberculosis infection in mice. Infection was monitored by physical (survival time and body weight) and bacteriological (viable counts in lungs) parameters. Compared with water, corn oil significantly improved both ...

Oral desensitization to milk: how to choose the starting dose!

Science.gov (United States)

Mori, Francesca; Pucci, Neri; Rossi, Maria Elisabetta; de Martino, Maurizio; Azzari, Chiara; Novembre, Elio

2010-01-01

Mori F, Pucci N, Rossi ME, de Martino M, Azzari C, Novembre E. Oral desensitization to milk: how to choose the starting dose! Pediatr Allergy Immunol 2010: 21: e450–e453. © 2009 John Wiley & Sons A/S A renewed interest in oral desensitization as treatment for food allergy has been observed in the last few years. We studied a novel method based on the end point skin prick test procedure to establish the starting dose for oral desensitization in a group of 30 children higly allergic to milk. The results (in terms of reactions to the first dose administered) were compared with a group of 20 children allergic to milk as well. Such control group started to swallow the same dose of 0.015 mg/ml of milk. None reacted to the first dose when administered according to the end point skin prick test. On the other side, ten out of 20 children (50%) from the control group showed mild allergic reactions to the first dose of milk. In conclusion the end point skin prick test procedure results safe and easy to be performed in each single child in order to find out the starting dose for oral desensitization to milk, also by taking into account the individual variability. PMID:19624618

Isavuconazole absorption following oral administration in healthy subjects is comparable to intravenous dosing, and is not affected by food, or drugs that alter stomach pH.

Science.gov (United States)

Schmitt-Hoffmann, Anne; Desai, Amit; Kowalski, Donna; Pearlman, Helene; Yamazaki, Takao; Townsend, Robert

2016-08-01

Two openlabel, single-dose, randomized crossover studies and one open-label, multiple-dose, parallel group study in healthy volunteers were conducted with the prodrug, isavuconazonium sulfate, to determine absolute bioavailability of the active triazole, isavuconazole (EudraCT 2007-004949-15; n = 14), and the effect of food (EudraCT 2007- 004940-63; n = 26), and pH (NCT02128893; n = 24) on the absorption of isavuconazole. Isavuconazonium sulfate 744 mg designed to deliver 400 mg of the active triazole isavuconazole was administered in the absolute bioavailability (oral or intravenous (IV) (2-hour infusion)) and food-effect studies (oral). In the pH-effect study, isavuconazonium sulfate 372 mg designed to deliver 200 mg of isavuconazole was administered orally three times daily (t.i.d.) for 2 days, followed by a single daily oral dose for 3 days, in the presence of steady state esomeprazole dosed orally at 40 mg/day. Isavuconazole was well tolerated in each study. Bioavailability: Geometric least squares mean ratios (GLSMR; oral/IV) for isavuconazole AUC∞, and Cmax were 98% (90% confidence interval (CI): 94, 101) and 78% (90% CI: 72, 85), respectively. Food-effect: GLSMR (fed/fasted) for AUC∞ and Cmax of isavuconazole in plasma were 110% (90% CI: 102, 118) and 92% (90% CI: 86, 98), respectively. Median tmax was 5 hours with food and 3 hours under fasted conditions. pH-effect: GLSMR for isavuconazole AUCtau and Cmax were 108% (90% CI: 89, 130) and 105% (90% CI: 89, 124), respectively. Orally administered isavuconazonium sulfate effectively delivers isavuconazole, as evidenced by the fact that oral isavuconazole is bioequivalent to the IV formulation. Dose adjustments are not required when switching between oral and IV formulations, regardless of food or drugs that increase gastric pH.

Absolute bioavailability of evacetrapib in healthy subjects determined by simultaneous administration of oral evacetrapib and intravenous [13C8]‐evacetrapib as a tracer

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Aburub, Aktham; Ward, Chris; Hinds, Chris; Czeskis, Boris; Ruterbories, Kenneth; Suico, Jeffrey G.; Royalty, Jane; Ortega, Demetrio; Pack, Brian W.; Begum, Syeda L.; Annes, William F.; Lin, Qun; Small, David S.

2015-01-01

This open‐label, single‐period study in healthy subjects estimated evacetrapib absolute bioavailability following simultaneous administration of a 130‐mg evacetrapib oral dose and 4‐h intravenous (IV) infusion of 175 µg [13C8]‐evacetrapib as a tracer. Plasma samples collected through 168 h were analyzed for evacetrapib and [13C8]‐evacetrapib using high‐performance liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameter estimates following oral and IV doses, including area under the concentration‐time curve (AUC) from zero to infinity (AUC[0‐∞]) and to the last measureable concentration (AUC[0‐tlast]), were calculated. Bioavailability was calculated as the ratio of least‐squares geometric mean of dose‐normalized AUC (oral : IV) and corresponding 90% confidence interval (CI). Bioavailability of evacetrapib was 44.8% (90% CI: 42.2–47.6%) for AUC(0‐∞) and 44.3% (90% CI: 41.8–46.9%) for AUC(0‐tlast). Evacetrapib was well tolerated with no reports of clinically significant safety assessment findings. This is among the first studies to estimate absolute bioavailability using simultaneous administration of an unlabeled oral dose with a 13C‐labeled IV microdose tracer at about 1/1000th the oral dose, with measurement in the pg/mL range. This approach is beneficial for poorly soluble drugs, does not require additional toxicology studies, does not change oral dose pharmacokinetics, and ultimately gives researchers another tool to evaluate absolute bioavailability. PMID:26639670

Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats.

Science.gov (United States)

Alam, Nausheen; Najam, Rahila

2015-01-01

Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose (8mg/kg/day) and at low dose (2mg/kg/day) of methylphenidate in 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed.

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

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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.

Failure of antimony trioxide to induce micronuclei or chromosomal aberrations in rat bone-marrow after sub-chronic oral dosing.

Science.gov (United States)

Kirkland, David; Whitwell, James; Deyo, James; Serex, Tessa

2007-03-05

Antimony trioxide (Sb2O3, CAS 1309-64-4) is widely used as a flame retardant synergist in a number of household products, as a fining agent in glass manufacture, and as a catalyst in the manufacture of various types of polyester plastics. It does not induce point mutations in bacteria or mammalian cells, but is able to induce chromosomal aberrations (CA) in cultured cells in vitro. Although no CA or micronuclei (MN) have been induced after acute oral dosing of mice, repeated oral dosing for 14 or 21 days resulted in increased CA in one report, but did not result in increased MN in another. In order to further investigate its in vivo genotoxicity, Sb2O3 was dosed orally to groups of rats for 21 days at 250, 500 and 1000 mg/kg day. There were no clinical signs of toxicity in the Sb2O3-exposed animals except for some reductions in body-weight gain in the top dose group. Toxicokinetic measurements in a separate study confirmed bone-marrow exposure, and at higher levels than would have been achieved by single oral dosing. Large numbers of cells were scored for CA (600 metaphases/sex group) and MN (12,000 PCE/sex group) but frequencies of CA or MN in Sb2O3-treated rats were very similar to controls, and not biologically or statistically different, at all doses. These results provide further indication that Sb2O3 is not genotoxic to the bone marrow of rodents after 21 days of oral administration at high doses close to the maximum tolerated dose.

Disintegration of chemotherapy tablets for oral administration in patients with swallowing difficulties.

Science.gov (United States)

Siden, Rivka; Wolf, Matthew

2013-06-01

The administration of oral chemotherapeutic drugs can be problematic in patients with swallowing difficulties. Inability to swallow solid dosage forms can compromise compliance and may lead to poor clinical outcome. The current technique of tablet crushing to aid in administration is considered an unsafe practice. By developing a technique to disintegrate tablets in an oral syringe, the risk associated with tablet crushing can be avoided. The purpose of this study was to determine the feasibility of using disintegration in an oral syringe for the administration of oral chemotherapeutic tablets. Eight commonly used oral chemotherapeutic drugs were tested. Tablets were placed in an oral syringe and allowed to disintegrate in tap water. Various volumes and temperatures were tested to identify which combination allows for complete disintegration of the tablet in the shortest amount of time. The oral syringe disintegration method was considered feasible if disintegration occurred in ≤15 min and in ≤20 mL of water and the dispersion passed through an oral syringe tip. The following tablets were shown to disintegrate within 15 min and in disintegration test. Disintegrating oral chemotherapeutic tablets in a syringe provides a closed system to administer hazardous drugs and allows for the safe administration of oral chemotherapeutic drugs in a tablet form to patients with swallowing difficulties.

Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol ...

African Journals Online (AJOL)

Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol-Induced Hepatotoxicity In Rats. ... Nigerian Quarterly Journal of Hospital Medicine ... the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure.

Sedative and antinociceptive effects of dexmedetomidine and buprenorphine after oral transmucosal or intramuscular administration in cats.

Science.gov (United States)

Porters, Nathalie; Bosmans, Tim; Debille, Mariëlla; de Rooster, Hilde; Duchateau, Luc; Polis, Ingeborgh

2014-01-01

To compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats. Randomized, 'blinded' crossover study, with 1 month washout between treatments. Six healthy neutered female cats, weighing 5.3-7.5 kg. A combination of dexmedetomidine (40 μg kg(-1) ) and buprenorphine (20 μg kg(-1) ) was administered by either the OTM (buccal cavity) or IM (quadriceps muscle) route. Sedation was measured using a numerical rating scale, at baseline and at various time points until 6 hours after treatment. At the same time points, analgesia was scored using a dynamic and interactive visual analogue scale, based on the response to an ear pinch, and by the cat's response to a mechanical stimulus exerted by a pressure rate onset device. Physiological and adverse effects were recorded, and oral pH measured. Signed rank tests were performed, with significance set at p < 0.05. Data are presented as median and range. There were no differences in sedation or antinociception scores between OTM and IM dosing at any of the time points. Nociceptive thresholds increased after both treatments but without significant difference between groups. Buccal pH remained between 8 and 8.5. Salivation was noted after OTM administration (n = 2) and vomiting after both OTM (n = 4), and IM (n = 3) dosing. In healthy adult cats, OTM administration of dexmedetomidine and buprenorphine resulted in comparable levels of sedation and antinociception to IM dosing. The OTM administration may offer an alternative route to administer this sedative-analgesic combination in cats. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Styrene maleic acid-encapsulated paclitaxel micelles: antitumor activity and toxicity studies following oral administration in a murine orthotopic colon cancer model

Directory of Open Access Journals (Sweden)

Parayath NN

2016-08-01

Full Text Available Neha N Parayath,1 Hayley Nehoff,1 Samuel E Norton,2 Andrew J Highton,2 Sebastien Taurin,1,3 Roslyn A Kemp,2 Khaled Greish1,4 1Department of Pharmacology and Toxicology, 2Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand; 3Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA; 4Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract: Oral administration of paclitaxel (PTX, a broad spectrum anticancer agent, is challenged by its low uptake due to its poor bioavailability, efflux through P-glycoprotein, and gastrointestinal toxicity. We synthesized PTX nanomicelles using poly(styrene-co-maleic acid (SMA. Oral administration of SMA-PTX micelles doubled the maximum tolerated dose (60 mg/kg vs 30 mg/kg compared to the commercially available PTX formulation (PTX [Ebewe]. In a murine orthotopic colon cancer model, oral administration of SMA-PTX micelles at doses 30 mg/kg and 60 mg/kg reduced tumor weight by 54% and 69%, respectively, as compared to the control group, while no significant reduction in tumor weight was observed with 30 mg/kg of PTX (Ebewe. In addition, toxicity of PTX was largely reduced by its encapsulation into SMA. Furthermore, examination of the tumors demonstrated a decrease in the number of blood vessels. Thus, oral delivery of SMA-PTX micelles may provide a safe and effective strategy for the treatment of colon cancer. Keywords: oral delivery, anticancer nanomedicine, CT-26, enhanced permeability and retention (EPR effect, HUVEC, antiangiogenic

Toxicokinetics and biotransformation of 3-(4-methylbenzylidene)camphor in rats after oral administration

International Nuclear Information System (INIS)

Voelkel, Wolfgang; Colnot, Thomas; Schauer, Ute M.D.; Broschard, Thomas H.; Dekant, Wolfgang

2006-01-01

3-(4-Methylbenzylidene)camphor (4-MBC) is an UV-filter frequently used in sunscreens and cosmetics. Equivocal findings in some screening tests for hormonal activity initiated a discussion on a possible weak estrogenicity of 4-MBC. In this study, the toxicokinetics and biotransformation of 4-MBC were characterized in rats after oral administration. Male and female Sprague-Dawley rats (n = 3 per group) were administered single oral doses of 25 or 250 mg/kg bw of 4-MBC in corn oil. Metabolites formed were characterized and the kinetics of elimination for 4-MBC and its metabolites from blood and with urine were determined. Metabolites of 4-MBC were characterized by 1 H NMR and LC-MS/MS as 3-(4-carboxybenzylidene)camphor and as four isomers of 3-(4-carboxybenzylidene)hydroxycamphor containing the hydroxyl group located in the camphor ring system with 3-(4-carboxybenzylidene)-6-hydroxycamphor as the major metabolite. After oral administration of 4-MBC, only very low concentrations of 4-MBC were present in blood and the peak concentrations of 3-(4-carboxybenzylidene)camphor were approximately 500-fold above those of 4-MBC; blood concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were below the limit of detection. Blood concentration of 4-MBC and 3-(4-carboxybenzylidene)camphor peaked within 10 h after 4-MBC administration and then decreased with half-lives of approximately 15 h. No major differences in peak blood levels between male and female rats were seen. In urine, one isomer of 3-(4-carboxybenzylidene)hydroxycamphor was the predominant metabolite [3-(4-carboxybenzylidene)-6-hydroxycamphor], the other isomers and 3-(4-carboxybenzylidene)camphor were only minor metabolites excreted with urine. However, urinary excretion of 4-MBC-metabolites represents only a minor pathway of elimination for 4-MBC, since most of the applied dose was recovered in feces as 3-(4-carboxybenzylidene)camphor and, to a smaller extent, as 3-(4-carboxybenzylidene)-6-hydroxycamphor

Repeated oral administration of capsaicin increases anxiety-like ...

Indian Academy of Sciences (India)

This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02% capsaicin into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of capsaicin. Stereotypy ...

Single dose oral piroxicam for acute postoperative pain

Science.gov (United States)

Moore, R Andrew; Edwards, Jayne; Loke, Yoon; Derry, Sheena; McQuay, Henry J

2014-01-01

Background This is an updated version of the original Cochrane review published in Issue 2, 2000. Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties, and is used mainly for treating rheumatic disorders. Some drugs have been directly compared against each other within a trial setting to determine their relative efficacies, whereas other have not. It is possible, however, to compare analgesics indirectly by examining the effectiveness of each drug against placebo when used in similar clinical situations. Objectives To determine the analgesic efficacy and adverse effects of single-dose piroxicam compared with placebo in moderate to severe postoperative pain. To compare the effects of piroxicam with other analgesics. Search methods Published studies were identified from systematic searching of MEDLINE, Biological Abstracts, EMBASE, CENTRAL and the Oxford Pain Relief Database in December 2007. Additional studies were identified from the reference lists of retrieved reports. Selection criteria The following inclusion criteria were used: full journal publication, randomised placebo controlled trial, double-blind design, adult participants, postoperative pain of moderate to severe intensity at the baseline assessment, postoperative administration of oral or intramuscular piroxicam. Data collection and analysis Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of participants obtaining at least 50% pain relief. This was used to calculate estimates of relative benefit and number-needed-to-treat-to-benefit (NNT) for one participant to obtain at least 50% pain relief. Information was collected on adverse effects and estimates of relative risk and number-needed-to-treat-to-harm (NNH) were calculated. Main results In this update no further studies were found. The original search identified three studies (141 participants) which compared oral piroxicam 20 mg with placebo and

Intermittent subcutaneous methadone administration in the management of cancer pain.

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Centeno, Carlos; Vara, Francisco

2005-01-01

Methadone is a strong opioid analgesic that has been used successfully in cancer pain management. The oral route of administration is generally preferred for opioid analgesics. However that route sometimes cannot be used. Experience with continuous subcutaneous methadone infusions has produced local intolerance. The aim of this study was to analyze the use of intermittent subcutaneous methadone injections. Ten patients whose pain was well-controlled with oral methadone (average dose 30 mg, range 10 to 120 mg) participated in the study. A subcutaneous small vein needle (butterfly) was used exclusively for administration of methadone. Over a period of seven days the local discomfort of each injection was evaluated by means of a Verbal Numerical Rating Scale (NRS) and the site of infusion was observed. When any degree of erythema or inflammation was seen, the infusion site was changed. The initial subcutaneous dose was the same as the previously administered oral dose. A daily record was kept of the dose used, level of pain, and toxicity symptoms. This close vigilance was aimed at avoiding dosage errors due to variations among individuals in acceptance to previous oral medication. Changes in dosage were allowed according to standard medical criteria. Two patients were withdrawn from the study due to non-painful irritation at the infusion point. Another eight patients tolerated repeated administration of subcutaneous methadone over seven days. Any local irritation from subcutaneous methadone that occurred was managed satisfactorily by changing the infusion site and limiting doses to 30 mg. In seven of 182 repeat administration, injection site changes were necessitated by local irritation. The NRS for local discomfort was 2/10. The two patients who were intolerant of the subcutaneous injections were receiving injected doses which were significantly higher than the others (42 mg as compared to 25 mg). Dose adjustments needed when changing from the oral to the

Administrative Challenges to the Integration of Oral Health With Primary Care

Science.gov (United States)

Maxey, Hannah L.; Randolph, Courtney; Gano, Laura; Kochhar, Komal

2017-01-01

Inadequate access to preventive oral health services contributes to oral health disparities and is a major public health concern in the United States. Federally Qualified Health Centers play a critical role in improving access to care for populations affected by oral health disparities but face a number of administrative challenges associated with implementation of oral health integration models. We conducted a SWOT (strengths, weaknesses, opportunities, and threats) analysis with health care executives to identify strengths, weaknesses, opportunities, and threats of successful oral health integration in Federally Qualified Health Centers. Four themes were identified: (1) culture of health care organizations; (2) operations and administration; (3) finance; and (4) workforce. PMID:27218701

Pharmacokinetics of enrofloxacin following oral and subcutaneous administration in the common ringtail possum (Pseudocheirus peregrinus).

Science.gov (United States)

Scheelings, T F; Devi, J L; Woodward, A P; Whittem, T

2015-10-01

[Correction added on 23 March 2015, after first online publication: Terminal half-life values of enrofloxacin is corrected in the fourth sentence of the abstract] Clinically healthy common ringtail possums (n = 5) received single doses of 10 mg/kg enrofloxacin orally and then 2 weeks later subcutaneously. Serial plasma samples were collected over 24 h for each treatment phase, and enrofloxacin concentrations were determined using a validated HPLC assay. Pharmacokinetic parameters were determined by noncompartmental analysis. Following oral administration, plasma concentrations were of therapeutic relevance (Cmax median 5.45 μg/mL, range 2.98-6.9 μg/mL), with terminal-phase half-life (t½ ) shorter than in other species (median 3.09 h, range 1.79-5.30 h). In contrast, subcutaneous administration of enrofloxacin did not achieve effective plasma concentrations, with plasma concentrations too erratic to fit the noncompartmental model except in one animal. On the basis of the AUC:MIC, enrofloxacin administered at 10 mg/kg orally, but not subcutaneously, is likely to be effective against a range of bacterial species that have been reported in common ringtail possums. © 2015 John Wiley & Sons Ltd.

Cannabinoids and metabolites in expectorated oral fluid after 8 days of controlled around-the-clock oral THC administration.

Science.gov (United States)

Milman, Garry; Barnes, Allan J; Schwope, David M; Schwilke, Eugene W; Goodwin, Robert S; Kelly, Deana L; Gorelick, David A; Huestis, Marilyn A

2011-08-01

Oral fluid (OF) is an increasingly accepted matrix for drug testing programs, but questions remain about its usefulness for monitoring cannabinoids. Expectorated OF specimens (n = 360) were obtained from 10 adult daily cannabis smokers before, during, and after 37 20-mg oral Δ(9)-tetrahydrocannabinol (THC) doses over 9 days to characterize cannabinoid disposition in this matrix. Specimens were extracted and analyzed by gas chromatography-mass spectrometry with electron-impact ionization for THC, 11-hydroxy-THC, cannabidiol, and cannabinol, and negative chemical ionization for 11-nor-9-carboxy-THC (THCCOOH). Linear ranges for THC, 11-hydroxy-THC, and cannabidiol were 0.25-50 ng/mL; cannabinol 1-50 ng/mL; and THCCOOH 5-500 pg/mL. THCCOOH was the most prevalent analyte in 344 specimens (96.9%), with concentrations up to 1,390.3 pg/mL. 11-hydroxy-THC, cannabidiol, and cannabinol were detected in 1, 1, and 3 specimens, respectively. THC was detected in only 13.8% of specimens. The highest THC concentrations were obtained at admission (median 1.4 ng/mL, range 0.3-113.6) from previously self-administered smoked cannabis. A total of 2.5 and 3.7% of specimens were THC-positive at the recommended Substance Abuse and Mental Health Services Administration (2 ng/mL) and Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) (1 ng/mL) confirmation cutoffs, respectively. THC is currently the only analyte for monitoring cannabis exposure in OF; however, these data indicate chronic therapeutic oral THC administration and illicit oral THC use are unlikely to be identified with current guidelines. Measurement of THCCOOH may improve the detection and interpretation of OF cannabinoid tests and minimize the possibility of OF contamination from passive inhalation of cannabis smoke.

Protective effects of orally applied fullerenol nano particles in rats after a single dose of doxorubicin

Directory of Open Access Journals (Sweden)

Ičević Ivana Đ.

2011-01-01

Full Text Available Polyhydroxylated, water soluble, fullerenol C60(OH24 nano particles (FNP in vitro and in vivo models, showed an expressive biological activity. The goal of this work was to investigate the potential protective effects of orally applied FNP on rats after a single dose of doxorubicin (DOX (8 mg/kg (i.p. 6 h after the last application of FNP. After the last drug administration, the rats were sacrificed, and the blood and tissues were taken for the analysis. Biochemical and pathological results obtained in this study indicate that fullerenol (FNP, in H2O:DMSO (80:20, w/w solution given orally in final doses of 10, 14.4, and 21.2 mg/kg three days successively, has the protective (hepatoprotective and nephroprotective effect against doxorubicin-induced cytotoxicity via its antioxidant properties.

HTO oral administration in mice: Pt. 1

International Nuclear Information System (INIS)

Yamamoto, O.; Yokoro, K.; Seyama, T.; Kinomura, A.; Nomura, T.

1990-01-01

Tritiated water in various concentrations was orally administered continuously to (C57BL/6N and C3H/He)F 1 female mice in a closed animal chamber. Tritium radioactivity in various organ tissues was measured periodically after initiating tritiated water intake using an automatic sample combustion system and a liquid scintillation counter. After 7 days the specific radioactivity reached a plateau. Within a range of 1.48 x 10 11 to 5.92 x 10 11 Bq/dm 3 as the concentration of tritiated water in drinking water, the time of death after initiating the administration was about 2 weeks, a typical time for haematopoietic death. A linear relationship of times of death with tritiated water concentrations in drinking water was observed, on a log-log scale, between 1.85 x 10 10 Bq/dm 3 and 1.48 x 10 11 Bq/dm 3 . At concentrations lower than 9.25 x 10 9 Bq/dm 3 , mice no longer died from haematopoietic failure. The authors conclude, therefore, that there should be a threshold dose rate for haematopoietic death. (author)

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

Practical considerations in medical cannabis administration and dosing.

Science.gov (United States)

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.

Continuous low-dose oral chemotherapy in recurrent and persistent carcinoma of cervix following chemoradiation: A comparative study between prolonged oral cyclophosphamide and oral etoposide

Directory of Open Access Journals (Sweden)

Upasana Baruah

2014-01-01

Full Text Available Aim: To compare the efficacy and toxicities of low-dose oral cyclophosphamide and oral etoposide in patients with persistent and recurrent cervical cancer with gross pelvic disease following full course of chemoradiation therapy. Materials and Methods: 30 patients with recurrent and persistent cervical cancer with gross pelvic disease were enrolled in this trial. The patients were randomly divided into two groups of 15 patients each with one group receiving low dose oral cyclophosphamide (100 mg/day and the other group receiving low-dose oral etoposide (50 mg/day. Results were statistically analysed by IBM SPSS Statistics 19. Results: Oral etoposide was not well tolerated with grade 2 neutropenia occurring in 33.3% and grade 3 neutropenia in 6.6% and thrombocytopenia occurring in 13.3%. Oral cyclophosphamide group on the other hand was better tolerated with none of the patients having thrombocytopenia and 6.6% patients having grade 2 neutropenia. There were two complete response (15.38% and one partial response at the end of study (7.6% in the cyclophosphamide group whereas there was no complete response and two partial response (16.6% in the oral etoposide group. Conclusion: Long-term, low-dose oral etoposide was found to be less tolerated without any significant effect with patients with persistent and recurrent cervical cancer with gross pelvic disease following full course of chemoradiation therapy in contrast to oral cyclophosphamide which was found to be effective and well-tolerated by the patients.

LC determination and pharmacokinetic study of the main phenolic components of Portulaca oleracea L. extract in rat plasma after oral administration.

Science.gov (United States)

Cheng, Zhongzhe; Wang, Dong; Zhang, Wenjie; Du, Yang; Wang, Yunjiao; Zhai, Yanjun; Ying, Xixiang; Kang, Tingguo

2012-01-01

This study investigated the pharmacokinetics of hesperidin (HP), ferulic acid (FA) and p-coumaric acid (CA) in rat plasma after oral administration of Portulaca oleracea L. extract (POE). The plasma concentrations were determined by HPLC with vitexin-2″-O-rhamnoside (VR) as internal standard. The calibration curves were linear over the range 0.1-5 µg mL(-1), 0.1-5 µg mL(-1)and 0.015-3 µg mL(-1) for HP, FA and CA, respectively. The validated method was suitable to the pharmacokinetic study of HP, FA and CA in rats after oral administration at a single dose of POE.

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

Directory of Open Access Journals (Sweden)

Mohamed Aboubakr

2014-01-01

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

Comparing the effects of low-dose contraceptive pills to control dysfunctional uterine bleeding by oral and vaginal methods.

Science.gov (United States)

Mehrabian, Ferdous; Abbassi, Fariba

2013-09-01

Background and Objective : Contraceptive pills are generally taken orally and can cause side effects such as nausea, vomiting and hypertension. The vaginal use of these pills can reduce such complications. Our objective was to compare the efficacy and side effects of low dose contraceptive pills by oral and vaginal route in the management of dysfunctional uterine bleeding-(DUB) Methods: This comparative observational study was conducted at Beheshti and Alzahra (SA) teaching hospitals, affiliated to Isfahan University of Medical Sciences in 2010-2011. One hundred women who presented with DUB were randomly assigned into two groups of equal number, receiving the low dose oral contraceptive pills by oral or vaginal route for three month. The amount and duration of bleeding were compared at the beginning and at the end of the study and side effects by these two methods compared. The results of this study showed that both oral and vaginal routes effectively reduced the duration and amount of bleeding due to DUB after three courses of treatment. This effect was better in the vaginal method compared with oral administration (P = 0.03). Regarding the side effects, nausea and vomiting were significantly higher in the oral group than in the vaginal group (P = 0.03). Vulvovaginitis infection was more frequent in the vaginal group than in the oral group (P = 0.03). Low dose contraceptive pills are effective in reducing the amount, time, and duration of bleeding in patients with DUB. In addition, reduction of gastrointestinal side effects by vaginal route helps to use these pills by the patient with proper training of physicians, midwives and patients.

Comparison of caffeine disposition following administration by oral solution (energy drink) and inspired powder (AeroShot) in human subjects.

Science.gov (United States)

Laizure, S Casey; Meibohm, Bernd; Nelson, Kembral; Chen, Feng; Hu, Zhe-Yi; Parker, Robert B

2017-12-01

To determine the disposition and effects of caffeine after administration using a new dosage form (AeroShot) that delivers caffeine by inspiration of a fine powder into the oral cavity and compare it to an equivalent dose of an oral solution (energy drink) as the reference standard. Healthy human subjects (n = 17) inspired a 100 mg caffeine dose using the AeroShot device or consumed an energy drink on separate study days. Heart rate, blood pressure and subject assessments of effects were measured over an 8-h period. Plasma concentrations of caffeine and its major metabolites were determined by liquid chromatography-mass spectrometry. Pharmacokinetic, cardiovascular and perceived stimulant effects were compared between AeroShot and energy drink phases using a paired t test and standard bioequivalency analysis. Caffeine disposition was similar after caffeine administration by the AeroShot device and energy drink: peak plasma concentration 1790 and 1939 ng ml -1 , and area under the concentration-time curve (AUC) 15 579 and 17 569 ng ml -1 × h, respectively, but they were not bioequivalent: AeroShot AUC of 80.3% (confidence interval 71.2-104.7%) and peak plasma concentration of 86.3% (confidence interval 62.8-102.8%) compared to the energy drink. Female subjects did have a significantly larger AUC compared to males after consumption of the energy drink. The heart rate and blood pressure were not significantly affected by the 100 mg caffeine dose, and there were no consistently perceived stimulant effects by the subjects using visual analogue scales. Inspiration of caffeine as a fine powder using the AeroShot device produces a similar caffeine profile and effects compared to administration of an oral solution (energy drink). © 2017 The British Pharmacological Society.

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults.

Science.gov (United States)

Brown, Randall T; Nicholas, Christopher R; Cozzi, Nicholas V; Gassman, Michele C; Cooper, Karen M; Muller, Daniel; Thomas, Chantelle D; Hetzel, Scott J; Henriquez, Kelsey M; Ribaudo, Alexandra S; Hutson, Paul R

2017-12-01

Psilocybin is a psychedelic tryptamine that has shown promise in recent clinical trials for the treatment of depression and substance use disorders. This open-label study of the pharmacokinetics of psilocybin was performed to describe the pharmacokinetics and safety profile of psilocybin in sequential, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg in 12 healthy adults. Eligible healthy adults received 6-8 h of preparatory counseling in anticipation of the first dose of psilocybin. The escalating oral psilocybin doses were administered at approximately monthly intervals in a controlled setting and subjects were monitored for 24 h. Blood and urine samples were collected over 24 h and assayed by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for psilocybin and psilocin, the active metabolite. The pharmacokinetics of psilocin were determined using both compartmental (NONMEM) and noncompartmental (WinNonlin) methods. No psilocybin was found in plasma or urine, and renal clearance of intact psilocin accounted for less than 2% of the total clearance. The pharmacokinetics of psilocin were linear within the twofold range of doses, and the elimination half-life of psilocin was 3 h (standard deviation 1.1). An extended elimination phase in some subjects suggests hydrolysis of the psilocin glucuronide metabolite. Variation in psilocin clearance was not predicted by body weight, and no serious adverse events occurred in the subjects studied. The small amount of psilocin renally excreted suggests that no dose reduction is needed for subjects with mild-moderate renal impairment. Simulation of fixed doses using the pharmacokinetic parameters suggest that an oral dose of 25 mg should approximate the drug exposure of a 0.3 mg/kg oral dose of psilocybin. Although doses of 0.6 mg/kg are in excess of likely therapeutic doses, no serious physical or psychological events occurred during or within 30 days of any dose. NCT02163707.

Low-dose intranasal versus oral midazolam for routine body MRI of claustrophobic patients

Energy Technology Data Exchange (ETDEWEB)

Tschirch, Frank T.C.; Goepfert, Kerstin; Brunner, Genevieve; Weishaupt, Dominik [University Hospital Zuerich, Institute of Diagnostic Radiology, Zuerich (Switzerland); Froehlich, Johannes M. [Klus-Apotheke, Zuerich (Switzerland)

2007-06-15

The purpose of this study was to assess prospectively the potential of low-dose intranasal midazolam compared to oral midazolam in claustrophobic patients undergoing routine body magnetic resonance imaging (MRI). Seventy-two adult claustrophobic patients referred for body MRI were randomly assigned to one of two treatment groups (TG1 and TG2). The 36 patients of TG1 received 7.5 mg midazolam orally 15 min before MRI, whereas the 36 patients of TG2 received one (or, if necessary, two) pumps of a midazolam nasal spray into each nostril immediately prior to MRI (in total, 1 or 2 mg). Patients' tolerance, anxiety and sedation were assessed using a questionnaire and a visual analogue scale immediately before and after MRI. Image quality was evaluated using a five-point-scale. In TG1, 18/36 MRI examinations (50%) had to be cancelled, the reduction of anxiety was insufficient in 12/18 remaining patients (67%). In TG2, 35/36 MRI examinations (97%) were completed successfully, without relevant adverse effects. MRI image quality was rated higher among patients of TG2 compared to TG1 (p<0.001). Low-dose intranasal midazolam is an effective and patient-friendly solution to overcome anxiety in claustrophobic patients in a broad spectrum of body MRI. Its anxiolytic effect is superior to that of the orally administrated form. (orig.)

Oral administration of amphotericin B nanoparticles: antifungal activity, bioavailability and toxicity in rats.

Science.gov (United States)

Radwan, Mahasen A; AlQuadeib, Bushra T; Šiller, Lidija; Wright, Matthew C; Horrocks, Benjamin

2017-11-01

Amphotericin B (AMB) is used most commonly in severe systemic life-threatening fungal infections. There is currently an unmet need for an efficacious (AMB) formulation amenable to oral administration with better bioavailability and lower nephrotoxicity. Novel PEGylated polylactic-polyglycolic acid copolymer (PLGA-PEG) nanoparticles (NPs) formulations of AMB were therefore studied for their ability to kill Candida albicans (C. albicans). The antifungal activity of AMB formulations was assessed in C. albicans. Its bioavalability was investigated in nine groups of rats (n = 6). Toxicity was examined by an in vitro blood hemolysis assay, and in vivo nephrotoxicity after single and multiple dosing for a week by blood urea nitrogen (BUN) and plasma creatinine (PCr) measurements. The MIC of AMB loaded to PLGA-PEG NPs against C. albicans was reduced two to threefold compared with free AMB. Novel oral AMB delivery loaded to PLGA-PEG NPs was markedly systemically available compared to Fungizone® in rats. The addition of 2% of GA to the AMB formulation significantly (p bioavailability from 1.5 to 10.5% and the relative bioavailability was > 790% that of Fungizone®. The novel AMB formulations showed minimal toxicity and better efficacy compared to Fungizone®. No nephrotoxicity in rats was detected after a week of multiple dosing of AMB NPs based on BUN and PCr, which remained at normal levels. An oral delivery system of AMB-loaded to PLGA-PEG NPs with better efficacy and minimal toxicity was formulated. The addition of glycyrrhizic acid (GA) to AMB NPs formulation resulted in a significant oral absorption and improved bioavailability in rats.

Pan-oral dose assessment: a comparative report of methodologies

International Nuclear Information System (INIS)

Shafford, J.; Pryor, M.; Hollaway, P.; Peet, D.; Oduko, J.

2015-01-01

National guidance from the Institute of Physics and Engineering in Medicine (IPEM Report 91) currently recommends that the patient dose for a pan-oral X-ray unit is measured as dose area product (DAP) replacing dose width product described in earlier guidance. An investigation identifying different methods available to carry out this measurement has been undertaken and errors in the methodologies analysed. It has been shown that there may be up to a 30 % variation in DAP measurement between methods. This paper recommends that where possible a DAP meter is used to measure the dose-area product from a pan-oral X-ray unit to give a direct DAP measurement. However, by using a solid-state dose measurement and film/ruler to calculate DAP the authors have established a conversion factor of 1.4. It is strongly recommended that wherever a DAP value is quoted the methodology used to obtain that value is also reported. (authors)

[Individualization of low-dose oral contraceptives. Pharmacological principles and practical indications for oral contraceptives].

Science.gov (United States)

Cianci, A; De Leo, V

2007-08-01

The contraceptive pill has been a revolution of the last 40 years. In Italy, however, it is much less widely used than in other countries. Explanations for this phenomenon range from religious implications and customs to misinformation and word-of-mouth communication of negative experiences. The oral contraceptive pill is often used to correct menstrual disorders, leading to poor results and side-effects. Recent advances in oral contraception have led to a substantial reduction in doses and side-effects. Low-dose pills contain minimal doses of progesterones and estrogens and ensure good control of the menstrual cycle. Although reduction of ethinyl estradiol (EE) concentrations has reduced the incidence of negative systemic side effects such as water retention, edema and swollen breasts, the low estrogen dose may be associated with spotting and hypomenorrhea or amenorrhea in the long term, as well as dyspareunia due to reduced vaginal trophism, which may induce women to suspend use of the drug. It is also true that only one type of estrogen is used in the pill, albeit at different doses, whereas the progesterone may differ and in many cases is the cause of common side-effects. The choice of progesterone therefore involves not only its effect on the endometrium in synergy with estrogen, but also possible residual androgenic activity which may have negative metabolic repercussions. Indeed, addition of a progesterone, especially androgen-derived, attenuates the positive metabolic effects of estrogen. Two new monophasic oral contraceptives were recently released. They contain 30 microg (Yasmin) or 20 muicrog (Yasminelle) EE and a new progesterone, drospirenone, derived from spirolactone, which has antiandrogenic and antimineralcorticoid activity similar to endogenous progesterone. Like progesterone, the drospirenone molecule is an aldosterone antagonist and has a natriuretic effect that opposes the sodium retention effect of EE. It may, therefore, help to prevent the

Human kinetics of orally and intravenously administered low-dose 1,2-(13)C-dichloroacetate.

Science.gov (United States)

Jia, Minghong; Coats, Bonnie; Chadha, Monisha; Frentzen, Barbara; Perez-Rodriguez, Javier; Chadik, Paul A; Yost, Richard A; Henderson, George N; Stacpoole, Peter W

2006-12-01

Dichloroacetate (DCA) is a putative environmental hazard, owing to its ubiquitous presence in the biosphere and its association with animal and human toxicity. We sought to determine the kinetics of environmentally relevant concentrations of 1,2-(13)C-DCA administered to healthy adults. Subjects received an oral or intravenous dose of 2.5 microg/kg of 1,2-(13)C-DCA. Plasma and urine concentrations of 1,2-(13)C-DCA were measured by a modified gas chromatography-tandem mass spectrometry method. 1,2-(13)C-DCA kinetics was determined by modeling using WinNonlin 4.1 software. Plasma concentrations of 1,2-(13)C-DCA peaked 10 minutes and 30 minutes after intravenous or oral administration, respectively. Plasma kinetic parameters varied as a function of dose and duration. Very little unchanged 1,2-(13)C-DCA was excreted in urine. Trace amounts of DCA alter its own kinetics after short-term exposure. These findings have important implications for interpreting the impact of this xenobiotic on human health.

New approach for food allergy management using low-dose oral food challenges and low-dose oral immunotherapies.

Science.gov (United States)

Yanagida, Noriyuki; Okada, Yu; Sato, Sakura; Ebisawa, Motohiro

2016-04-01

A number of studies have suggested that a large subset of children (approximately 70%) who react to unheated milk or egg can tolerate extensively heated forms of these foods. A diet that includes baked milk or egg is well tolerated and appears to accelerate the development of regular milk or egg tolerance when compared with strict avoidance. However, the indications for an oral food challenge (OFC) using baked products are limited for patients with high specific IgE values or large skin prick test diameters. Oral immunotherapies (OITs) are becoming increasingly popular for the management of food allergies. However, the reported efficacy of OIT is not satisfactory, given the high frequency of symptoms and requirement for long-term therapy. With food allergies, removing the need to eliminate a food that could be consumed in low doses could significantly improve quality of life. This review discusses the importance of an OFC and OIT that use low doses of causative foods as the target volumes. Utilizing an OFC or OIT with a low dose as the target volume could be a novel approach for accelerating the tolerance to causative foods. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Two cases of corneal perforation after oral administration of nonsteroidal anti-inflammatory drugs: oral NSAID-induced corneal damage.

Science.gov (United States)

Masuda, Ikuya; Matsuo, Toshihiko; Okamoto, Kazuo; Matsushita, Kyoko; Ohtsuki, Hiroshi

2010-01-01

To report 2 cases of corneal perforation associated with the use of oral nonsteroidal anti-inflammatory drugs (NSAIDs). In a 62-year-old woman and a 79-year-old woman, corneal perforation occurred after 7 days and 5 months of oral NSAIDs administration, respectively. After NSAIDs were discontinued, the cornea epithelialized and the anterior chamber formed within 14 and 10 days, respectively. It is well known that topical NSAIDs cause corneal perforation. Observations in the present cases suggest that the oral administration of NSAIDs may also cause corneal damage, and hence, medical professionals should consider the risk of damage to the cornea when administering these drugs orally.

Fetal absorbed doses by radiopharmaceutical administration

International Nuclear Information System (INIS)

Rojo, Ana M; Gomez Parada, Ines M.; Di Trano, Jose L.

2000-01-01

The radiopharmaceutical administration with diagnostic or therapeutic purpose during pregnancy implies a prenatal radiation dose. The dose assessment and the evaluation of the radiological risks become relevant due to the great radiosensitivity of the fetal tissues in development. This paper is a revision of the available data for estimating fetal doses in the cases of the more frequently used radiopharmaceuticals in nuclear medicine, taking into account recent investigation in placental crossover. The more frequent diagnostic and therapeutic procedures were analyzed according to the radiation doses implied. (author)

Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin

International Nuclear Information System (INIS)

Gonzalez, S.; Pathak, M.A.; Fitzpatrick, T.B.; Cuevas, J.; Villarrubia, V.G.

1997-01-01

Sunburn, immune suppression, photo-aging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photo-protection, are helpful and can be achieved by topical sun-screening agents. Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo immunomodulating properties. Its beneficial photo-protective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photo-protective property of natural extract of PL after topical application or oral ingestion. Twenty-one healthy volunteers [either untreated or treated with oral psoralens (8-MOP or 5-MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of PL. Immunohistochemical assessment of CD1a-expressing epidermal cells were also performed. PL was found to be photo-protective after topical application as well as oral administration. PL increased UV dose required for IPD (P<0.01), MED (P<0.001) and MPD (P<0.001). After oral administration of PL, MED increased 2.,8±0.59 times and MPD increased 2.75±0.5 and 6.8±1.3 times depending upon the type of psoralen used. Immunohistochemical study revealed photo-protection of Langherhans cells by oral as well as topical PL. The observed photo-protective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photo-protection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such photo-therapies. (au)

Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin

Energy Technology Data Exchange (ETDEWEB)

Gonzalez, S.; Pathak, M.A.; Fitzpatrick, T.B. [Massachusetts General Hospital, Harvard Medical School, Dept. of Dermatology, Boston, MA (United States); Cuevas, J. [Hospital Universitario de Guadalajara, Dept. of Pathology, Guadalajara (Spain); Villarrubia, V.G. [I.F. Cantabria SA, Medical Dept., Immunology Sect., Madrid (Spain)

1997-12-31

Sunburn, immune suppression, photo-aging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photo-protection, are helpful and can be achieved by topical sun-screening agents. Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo immunomodulating properties. Its beneficial photo-protective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photo-protective property of natural extract of PL after topical application or oral ingestion. Twenty-one healthy volunteers [either untreated or treated with oral psoralens (8-MOP or 5-MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of PL. Immunohistochemical assessment of CD1a-expressing epidermal cells were also performed. PL was found to be photo-protective after topical application as well as oral administration. PL increased UV dose required for IPD (P<0.01), MED (P<0.001) and MPD (P<0.001). After oral administration of PL, MED increased 2.,8{+-}0.59 times and MPD increased 2.75{+-}0.5 and 6.8{+-}1.3 times depending upon the type of psoralen used. Immunohistochemical study revealed photo-protection of Langherhans cells by oral as well as topical PL. The observed photo-protective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photo-protection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such photo-therapies. (au). 50 refs.

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

Science.gov (United States)

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.

Brachytherapy for early oral tongue cancer. Low dose rate to high dose rate

International Nuclear Information System (INIS)

Yamazaki, Hideya; Inoue, Takehiro; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Inoue, Toshihiko; Furukawa, Souhei; Kakimoto, Naoya

2003-01-01

To examine the compatibility of low dose rate (LDR) with high dose rate (HDR) brachytherapy, we reviewed 399 patients with early oral tongue cancer (T1-2N0M0) treated solely by brachytherapy at Osaka University Hospital between 1967 and 1999. For patients in the LDR group (n=341), the treatment sources consisted of Ir-192 pin for 227 patients (1973-1996; irradiated dose, 61-85 Gy; median, 70 Gy), Ra-226 needle for 113 patients (1967-1986; 55-93 Gy; median, 70 Gy). Ra-226 and Ir-192 were combined for one patient. Ir-192 HDR (microSelectron-HDR) was used for 58 patients in the HDR group (1991-present; 48-60 Gy; median, 60 Gy). LDR implantations were performed via oral and HDR via a submental/submandibular approach. The dose rates at the reference point for the LDR group were 0.30 to 0.8 Gy/h, and for the HDR group 1.0 to 3.4 Gy/min. The patients in the HDR group received a total dose of 48-60 Gy (8-10 fractions) during one week. Two fractions were administered per day (at least a 6-h interval). The 3- and 5-year local control rates for patients in the LDR group were 85% and 80%, respectively, and those in the HDR group were both 84%. HDR brachytherapy showed the same lymph-node control rate as did LDR brachytherapy (67% at 5 years). HDR brachytherapy achieved the same locoregional result as did LDR brachytherapy. A converting factor of 0.86 is applicable for HDR in the treatment of early oral tongue cancer. (author)

Alteration of the systemic and microcirculation by a single oral dose of flavan-3-ols.

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Kodai Ingawa

Full Text Available Several systematic reviews have reported that flow mediated dilatation (FMD was significantly increased in subjects after ingestion of chocolate that contains flavan-3-ols; however, the mechanisms responsible for this effect are not clear. In this study, we evaluated the effects of a single oral dose of flavan-3-ols on the systemic circulation and microcirculation in the cremaster muscle using intravital video microscopy in vivo. The cremaster muscle in rats was spread over a plastic chamber and a gastric tube was placed into the stomach. Blood flow in the cremasteric artery was determined using a laser Doppler flowmeter, while blood pressure and heart rate were measured by the tail-cuff method. Red blood cell velocity in arterioles and blood flow in the artery were significantly increased 5 min after the administration of 10 mg/kg flavan-3-ols compared with distilled water treatment. The number of capillaries recruited in the cremaster muscle was also significantly increased 15 min after treatment. Microscopic observation confirmed that increased shear stress on endothelial cells was maintained during the measurement period. The mean arterial blood pressure and heart rate were also significantly elevated soon after administration and returned to baseline before the end of the observation period. Plasma nitrate and nitrite levels, and NO phosphorylation of aortic tissue were significantly increased at 60 min after administration of flavan-3-ols. According to these results, a single oral dose of flavan-3-ols elevates blood pressure and flow transiently, and these effects induce NO production through increased shear stress on endothelial cells.

Fluralaner as a single dose oral treatment for Caparinia tripilis in a pygmy African hedgehog.

Science.gov (United States)

Romero, Camilo; Sheinberg Waisburd, Galia; Pineda, Jocelyn; Heredia, Rafael; Yarto, Enrique; Cordero, Alberto M

2017-12-01

African pygmy hedgehogs (Atelerix albiventris) are popular pets belonging to the Erinaceidae family of spined mammals. Amongst the most common skin diseases occurring in this species is infestation caused by the mite Caparinia spp. Due to their skin anatomy and spiny coat, detection of skin lesions in these hedgehogs can be difficult. This may result in delays in seeking medical care, which may lead to secondary bacterial infection and self-inflicted trauma. Multiple therapies have been used in the treatment of this skin condition including ivermectin, amitraz, fipronil and selamectin. A drug which could be administered as a single oral dose would be advantageous to these pets and their owners. To evaluate the effect of a single oral dose (15 mg/kg) of fluralaner on Caparinia tripilis infestation in the African pygmy hedgehog. A 10-month-old African pygmy hedgehog weighing 184 g. Response to treatment was monitored by dermatological examination and superficial skin scrapings repeated at 7, 14, 21, 30, 60, 90 and 120 days following fluralaner administration. On Day 7 after treatment, adult mites were observed exhibiting normal movement. On Day 14, only dead mites were observed. No life stages of the mites were found after Day 21. A single oral dose at 15 mg/kg of fluralaner was effective within 21 days after treatment for capariniasis in this case. Further studies are required to evaluate the drug's safety and toxicology in hedgehogs, and to confirm efficacy. © 2017 ESVD and ACVD.

Effect of the dose and route of administration of butylscopolamine on the reduction of the artifacts associated with intestinal peristalsis in abdominal magnetic resonance

International Nuclear Information System (INIS)

Dosda, R.; Marti-Bonmati, L.; Ronchera-Oms, C.

1999-01-01

To compare the effect of the route of administration (intravenous and oral) and the dose (40 mg and 80 mg) of butylscopolamine, determining its efficacy in reducing the noise associated with gastrointestinal movement in magnetic resonance (MR) images and the incidence and severity of associated adverse reactions. The present prospective, controlled, double-blind study included 80 patients who underwent abdominal MR. All the patients were given oral, high-density barium sulfate and were divided randomly into 4 groups of 20 patients each: a control group and 3 groups treated with 40 mg or 80 mg of oral butylscopolamine or 40 mg of intravenous butylscopolamine. Both the barium and the oral solutions were administered 25 to 30 minutes before the examination. the MR images were obtained with a STIR sequence (1487/100/44), and qualitative analysis of the noise was carried out using regions of interest situated in the background. The gastrointestinal noise was defined both by the mean and the standard deviation of the signal intensity of the air front of an behind the patient. The standard deviation of the air beside the patient was determined to confirm the absence of variations in noise inherent to MR. The adverse reactions to MR after 2 hours (immediate) and one day (late) were recorded. There were no significant differences among the groups with respect to sex, age or time interval between administration of the oral solution and the start of the sequence. The noise inherent to MR was not significantly different from one group to another (Student-Newman-Keuls test, p=0.71). Both the mean and the standard deviation of the intensity of the air situated in anteroposterior phase-encoding direction were significantly lower in the butylscopolamine groups than in the control group (Student-Newman-Keuls test, p=0.008). The most marked reduction was observed after the oral dose of 80 mg, followed by intravenous injection of 40 mg and the oral dose of 40 mg. Adverse reaction

Human urinary excretion profile after smoking and oral administration of [14C]delta 1-tetrahydrocannabinol

International Nuclear Information System (INIS)

Johansson, E.; Gillespie, H.K.; Halldin, M.M.

1990-01-01

The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of [ 14 C]delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of 14 C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings were similar to the excretion profile of 14 C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively

SODIUM BICARBONATE FACILITATES LOW-DOSE ORAL TOLERANCE TO PEANUT IN MICE

Science.gov (United States)

Rationale: Oral tolerance specifically inhibits production of allergic IgE antibody and is therefore a potential method for suppressing food allergy. We have previously demonstrated that a single oral dose of one mg is sufficient to induce oral tolerance to egg white but not pean...

A double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]-basimglurant and absolute bioavailability after oral administration and concomitant intravenous microdose administration of [13C6]-labeled basimglurant in humans.

Science.gov (United States)

Guerini, Elena; Schadt, Simone; Greig, Gerard; Haas, Ruth; Husser, Christophe; Zell, Manfred; Funk, Christoph; Hartung, Thomas; Gloge, Andreas; Mallalieu, Navita L

2017-02-01

1. The emerging technique of employing intravenous microdose administration of an isotope tracer concomitantly with an [ 14 C]-labeled oral dose was used to characterize the disposition and absolute bioavailability of a novel metabotropic glutamate 5 (mGlu5) receptor antagonist under clinical development for major depressive disorder (MDD). 2. Six healthy volunteers received a single 1 mg [ 12 C/ 14 C]-basimglurant (2.22 MBq) oral dose and a concomitant i.v. tracer dose of 100 μg of [ 13 C 6 ]-basimglurant. Concentrations of [ 12 C]-basimglurant and the stable isotope [ 13 C 6 ]-basimglurant were determined in plasma by a specific LC/MS-MS method. Total [ 14 C] radioactivity was determined in whole blood, plasma, urine and feces by liquid scintillation counting. Metabolic profiling was conducted in plasma, urine, blood cell pellet and feces samples. 3. The mean absolute bioavailability after oral administration (F) of basimglurant was ∼67% (range 45.7-77.7%). The major route of [ 14 C]-radioactivity excretion, primarily in form of metabolites, was in urine (mean recovery 73.4%), with the remainder excreted in feces (mean recovery 26.5%). The median t max for [ 12 C]-basimglurant after the oral administration was 0.71 h (range 0.58-1.00) and the mean terminal half-life was 77.2 ± 38.5 h. Terminal half-life for the [ 14 C]-basimglurant was 178 h indicating presence of metabolites with a longer terminal half-life. Five metabolites were identified with M1-Glucuronide as major and the others in trace amounts. There was minimal binding of drug to RBCs. IV pharmacokinetics was characterized with a mean ± SD CL of 11.8 ± 7.4 mL/h and a Vss of 677 ± 229 L. 4. The double-tracer technique used in this study allowed to simultaneously characterize the absolute bioavailability and disposition characteristics of the new oral molecular entity in a single study.

effect of oral administration of aqueous extract of cassia occidentalis

African Journals Online (AJOL)

DR. AMINU

seeds extract's relation with acid – base balance of the body. Serum concentrations ... Oral administration of aqueous extract of C. occidentalis ... irrespective of duration of administration (weeks). .... Student 't' test was used to analyse the data.

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.

Rapid absorption of diclofenac and acetaminophen after their oral administration to cattle.

Science.gov (United States)

Sawaguchi, Akiyo; Sasaki, Kazuaki; Miyanaga, Keisuke; Nakayama, Mitsuhiro; Nagasue, Masato; Shimoda, Minoru

2016-10-01

The oral pharmacokinetics of diclofenac (DF) were evaluated in cattle by analyzing plasma concentration-time data after its intravenous and oral administration in order to propose the oral administration of DF as effective route to avoid long withdraw period. DF was intravenously and orally administered at 1 mg/kg to cattle using a crossover design with a 4-week washout period. Plasma concentrations of DF were determined by a HPLC analysis. The mean absorption time (MAT) and absorption half-life (t 1/2ka ) were 1.61 ± 0.61 and 1.51 ± 0.38 hr, respectively, and bioavailability was nearly 100%. The oral pharmacokinetics of acetaminophen (AAP) were also evaluated in cattle. Plasma concentrations of AAP were determined by a HPLC analysis. MAT and t 1/2ka were 2.85 ± 0.93 and 1.53 ± 0.28 hr, respectively, and bioavailability was approximately 70%. In conclusion, the results of the present study indicate that DF and AAP are rapidly absorbed from the forestomach of cattle. Therefore, the appropriate efficacies of these drugs may be achieved via their oral administration, even in cattle.

Stimulatory effect of oral administration of tea, coffee or caffeine on UVB-induced apoptosis in the epidermis of SKH-1 mice

International Nuclear Information System (INIS)

Conney, Allan H.; Zhou, Sherry; Lee Maojung; Xie Jianguo; Yang, Chung S.; Lou Yourong; Lu Yaoping

2007-01-01

Oral administration of green tea or a caffeine solution, but not decaffeinated green tea, inhibits UVB-induced complete carcinogenesis in SKH-1 mice. Oral administration of green tea, coffee or a caffeine solution for 2 weeks enhanced UVB-induced increases in apoptosis in the epidermis, but these treatments had no effect in non-UVB treated normal epidermis. Our results suggest that administration of green tea, coffee and caffeine may inhibit UVB-induced carcinogenesis - at least in part - by enhancing UVB-induced apoptosis. Plasma levels of caffeine observed after its oral administration at cancer-preventive dose levels were within the range observed in moderate coffee drinkers. Topical applications of caffeine to mice previously treated with UVB for 20 weeks (high risk mice without tumors) inhibited the formation of tumors and stimulated apoptosis in the tumors but not in areas of the epidermis away from tumors. The selective effects of caffeine administration to stimulate UVB-induced apoptosis or apoptosis in tumors but not in normal epidermis or in areas of the epidermis away from tumors is of considerable interest, but the reasons for the selective effects of caffeine on apoptosis in DNA damaged tissues are unknown. Further studies are needed to determine mechanisms of these effects of caffeine and to determine the effects of caffeine administration on sunlight-induced actinic keratoses and squamous cell carcinomas in humans

Effect of oral administration of terephthalic acid on testicular functions of rats

International Nuclear Information System (INIS)

Cui Lunbiao; Dai Guidong; Xu Lichun; Wang Shouling; Song Ling; Zhao Renzhen; Xiao Hang; Zhou Jianwei; Wang Xinru

2004-01-01

To investigate the toxic effect of terephthalic acid (TPA) on testicular functions of rats, male Sprague-Dawley rats were orally administered TPA in diet at the levels 0 (control), 0.2, 1 and 5% for 90 days. Testicular functions were assessed by histopathology, testicular sperm head counts, daily sperm production, sperm motility (measured by computer-assisted sperm analysis, CASA), biochemical indices (marker testicular enzymes), and serum testosterone. Oral feeding with terephthalic acid did not cause body and testes weight loss in TPA-treated groups. Histopathologically, damages of spermatogenic cells and Sertoli cells were observed by electron microscope, testicular sperm head counts, daily sperm production, and activities of sorbitol dehydrogenase (SDH) were decreased significantly in the 5% TPA group. The motility of spermatozoa was reduced significantly in all treated groups, which was correlated with administration doses. Serum testosterone concentrations were not declined in treated groups. In conclusion, TPA can cause impairment of testicular functions. The primary sites of action may be spermatogenic cells and Sertoli cells. The results of the present study provide first information of TPA on testicular functions in male rats

Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects.

Science.gov (United States)

Wilhelmus, Micha Mm; Hay, Justin L; Zuiker, Rob Gja; Okkerse, Pieter; Perdrieu, Christelle; Sauser, Julien; Beaumont, Maurice; Schmitt, Jeroen; van Gerven, Joop Ma; Silber, Beata Y

2017-02-01

Caffeine induces positive effects on sustained attention, although studies assessing the acute effects of low caffeine dose (caffeine on sustained attention in tests lasting up to 45 minutes using 82 low or non-caffeine-consuming healthy male ( n=41) and female ( n=41) adults aged between 40 and 60 years. Vigilance was measured using Mackworth Clock test, Rapid Visual Information Processing Test, adaptive tracking test, saccadic eye movement and attention switch test. Effects on mood and fatigue were analysed using Bond and Lader and Caffeine Research visual analogue scales, and Samn-Perelli questionnaire. Saliva sampling was performed for both compliance and caffeine pharmacokinetic analysis. Administration of a 60 mg caffeine dose resulted in a significant improvement in sustained attention compared with the placebo. Also a significantly improved peak saccadic velocity and reaction time performance was found, and decreased error rate. Significantly increased feelings of alertness, contentment and overall mood after caffeine treatment compared with placebo were observed. This study demonstrated that in healthy adult subjects oral administration of a single 60 mg caffeine dose elicited a clear enhancement of sustained attention and alertness, measured both in multiple objective performances and in subjective scales.

Intralesional Versus Oral Chloroquine in Cutaneous Leishmaniasis: Comparison of Outcome, Duration of Treatment and Total Dose of Drug

International Nuclear Information System (INIS)

Hanif, M. M.; Akram, K.; Mustafa, G.

2016-01-01

Objective: To compare intralesional versus oral chloroquine in cutaneous leishmaniasis and determine the cure rate, duration of treatment, and total dose of drug. Study Design: Randomized controlled study. Place and Duration of Study: Department of Dermatology, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, from November 2013 to June 2014. Methodology: Consecutive 86 patients of cutaneous leishmaniasis, with single to multiple lesions of various sizes were enrolled and divided randomly into group A and B for the purpose of intralesional and oral chloroquine administration, respectively to compare the effect of the two routes on duration of treatment and total dose of the drug. SPSS version 16 was used for data analysis after data entry into it. Quantitative variables like, duration, cost and total dose of treatment were calculated as mean and standard deviation and compared by using T-test. P-value of less than 0.05 was taken as significant. Results: Cure rate was 100% in both groups towards the end of treatment. Mean duration of treatment was 9.17 ± 3 weeks in intralesional (A) group as against 11.37 ± 3 weeks in oral (B) group (p = 0.0028). Mean total dose of the drug given to each patient in group A was 5.8 ± 0.5 gm and in group B, it was 19.2 ± 1.5 gm, which is significantly higher (p=0.001). The total cost of treatment in group A was Rs. 90 ± 8 and in group B it was Rs. 91 ± 1 (p=0.446). Conclusion: Duration of treatment is significantly shorter and total dose is lesser with intralesional compared to oral chloroquine in treatment of cutaneous leishmaniasis. (author)

Oral administration of insulin by means of liposomes in animal experiments

International Nuclear Information System (INIS)

Tragl, K.H.; Pohl, A.; Kinast, H.

1979-01-01

Liposomes are an effective vehicle for the oral administration of insulin. They are prepared from lipid emulsions by sonication and particles of homogeneous size are generated by elution through sepharose columns. Liposomes are taken up into the gastric mucosa by endocytosis and then transported to the liver via the portal circulation. Oral administration of 10 U insulin/kg body weight to rats is followed by a reduction in blood glucose to 67% of the initial value. When liposome-trapped insulin was injected intravenously a decrease in blood glucose to 40% of the initial value was obtained by the administration of 5 IU insulin/kg body weight. While the effect of orally-administered liposome-trapped insulin is obvious, the problems of standardization of the insulin content of the liposomes and the great variability of liposome uptake into the gastric mucosa by endocytosis remain unsolved. (author)

Can oral fluid cannabinoid testing monitor medication compliance and/or cannabis smoking during oral THC and oromucosal Sativex administration?

Science.gov (United States)

Lee, Dayong; Karschner, Erin L; Milman, Garry; Barnes, Allan J; Goodwin, Robert S; Huestis, Marilyn A

2013-06-01

We characterize cannabinoid disposition in oral fluid (OF) after dronabinol, synthetic oral Δ(9)-tetrahydrocannabinol (THC), and Sativex, a cannabis-extract oromucosal spray, and evaluate whether smoked cannabis relapse or Sativex compliance can be identified with OF cannabinoid monitoring. 5 and 15 mg synthetic oral THC, low (5.4 mg THC, 5.0 mg cannabidiol (CBD)) and high (16.2 mg THC, 15.0 mg CBD) dose Sativex, and placebo were administered in random order (n=14). Oral fluid specimens were collected for 10.5 h after dosing and analyzed for THC, CBD, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH). After oral THC, OF THC concentrations decreased over time from baseline, reflecting residual THC excretion from previously self-administered smoked cannabis. CBD and CBN also were rarely detected. After Sativex, THC, CBD and CBN increased greatly, peaking at 0.25-1 h. Median CBD/THC and CBN/THC ratios were 0.82-1.34 and 0.04-0.06, respectively, reflecting cannabinoids' composition in Sativex. THCCOOH/THC ratios within 4.5 h post Sativex were ≤ 1.6 pg/ng, always lower than after oral THC and placebo. THCCOOH/THC ratios increased throughout each dosing session. Lack of measurable THC, CBD and CBN in OF following oral THC, and high OF CBD/THC ratios after Sativex distinguish oral and sublingual drug delivery routes from cannabis smoking. Low THCCOOH/THC ratios suggest recent Sativex and smoked cannabis exposure. These data indicate that OF cannabinoid monitoring can document compliance with Sativex pharmacotherapy, and identify relapse to smoked cannabis during oral THC medication but not Sativex treatment, unless samples were collected shortly after smoking. Published by Elsevier Ireland Ltd.

Effects of sub acute oral administration of aqueous extract of ...

African Journals Online (AJOL)

The study evaluates the effects of sub acute oral administration (28 days) of aqueous extract of Stereospermum kunthianum stem bark on the body weight and haematological indices of rats. Treatments were administered by oral gavage once daily for a total of 28 days. The first group (control) received distilled water (5 ...

Human urinary excretion profile after smoking and oral administration of ( sup 14 C)delta 1-tetrahydrocannabinol

Energy Technology Data Exchange (ETDEWEB)

Johansson, E.; Gillespie, H.K.; Halldin, M.M. (BMC, Uppsala (Sweden))

1990-05-01

The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of ({sup 14}C)delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of {sup 14}C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings were similar to the excretion profile of {sup 14}C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively.

Pharmacokinetic Profile of Oral Cannabis in Humans: Blood and Oral Fluid Disposition and Relation to Pharmacodynamic Outcomes.

Science.gov (United States)

Vandrey, Ryan; Herrmann, Evan S; Mitchell, John M; Bigelow, George E; Flegel, Ronald; LoDico, Charles; Cone, Edward J

2017-03-01

Most research on cannabis pharmacokinetics has evaluated inhaled cannabis, but oral ("edible") preparations comprise an increasing segment of the cannabis market. To assess oral cannabis pharmacokinetics and pharmacodynamics, healthy adults (N = 6 per dose) were administered cannabis brownies containing 10, 25 or 50 mg 9-tetrahydrocannabinol (THC). Whole blood and oral fluid specimens were obtained at baseline and then for 9 days post-exposure; 6 days in a residential research setting and 3 days as outpatients. Measures of subjective, cardiovascular and performance effects were obtained at baseline and for 8 h post-ingestion. The mean Cmax for THC in whole blood was 1, 3.5 and 3.3 ng/mL for the 10, 25 and 50 mg THC doses, respectively. The mean maximum concentration (Cmax) and mean time to maximum concentration (Tmax) of 11-OH-THC in whole blood were similar to THC. Cmax blood concentrations of THCCOOH were generally higher than THC and had longer Tmax values. The mean Tmax for THC in oral fluid occurred immediately following oral dose administration, and appear to reflect local topical residue rather than systemic bioavailbility. Mean Cmax oral fluid concentrations of THCCOOH were lower than THC, erratic over time and mean Tmax occurred at longer times than THC. The window of THC detection ranged from 0 to 22 h for whole blood (limit of quantitation (LOQ) = 0.5 ng/mL) and 1.9 to 22 h for oral fluid (LOQ = 1.0 ng/mL). Subjective drug and cognitive performance effects were generally dose dependent, peaked at 1.5-3 h post-administration, and lasted 6-8 h. Whole blood cannabinoid concentrations were significantly correlated with subjective drug effects. Correlations between blood cannabinoids and cognitive performance measures, and between oral fluid and all pharmacodynamic outcomes were either non-significant or not orderly by dose. Quantitative levels of cannabinoids in whole blood and oral fluid were low compared with levels observed following inhalation of

High dose rate brachytherapy for oral cancer.

Science.gov (United States)

Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Furukawa, Souhei; Koizumi, Masahiko; Ogawa, Kazuhiko

2013-01-01

Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.

Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea In Vivo

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Victoria A. Meliopoulos

2016-11-01

Full Text Available The disease mechanisms associated with the onset of astrovirus diarrhea are unknown. Unlike other enteric virus infections, astrovirus infection is not associated with an inflammatory response or cellular damage. In vitro studies in differentiated Caco-2 cells demonstrated that human astrovirus serotype 1 (HAstV-1 capsid protein alone disrupts the actin cytoskeleton and tight junction complex, leading to increased epithelial barrier permeability. In this study, we show that oral administration of purified recombinant turkey astrovirus 2 (TAstV-2 capsid protein results in acute diarrhea in a dose- and time-dependent manner in turkey poults. Similarly to that induced by infectious virus, TAstV-2 capsid-induced diarrhea was independent of inflammation or histological changes but was associated with increased intestinal barrier permeability, as well as redistribution of sodium hydrogen exchanger 3 (NHE3 from the membrane to the cytoplasm of the intestinal epithelium. Unlike other viral enterotoxins that have been identified, astrovirus capsid induces diarrhea after oral administration, reproducing the natural route of infection and demonstrating that ingestion of intact noninfectious capsid protein may be sufficient to provoke acute diarrhea. Based on these data, we hypothesize that the astrovirus capsid acts like an enterotoxin and induces intestinal epithelial barrier dysfunction.

Fourteen days oral administration of therapeutic dosage of some ...

African Journals Online (AJOL)

Fourteen days oral administration of therapeutic dosage of some antibiotics reduced serum testosterone in male rats. FO Awobajo, Y Raji, II Olatunji-Bello, FT Kunle-Alabi, AO Adesanya, TO Awobajo ...

Split high-dose oral levothyroxine treatment as a successful therapy option in myxedema coma.

Science.gov (United States)

Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

2017-10-01

High-dose intravenous thyroxine (T4) is the preferable treatment for myxedema coma. We describe the clinical course of a 69-year-old man who presented with myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split dose. This suggests split high-dose oral LT4 as a therapeutic option in myxedema coma.

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

DEFF Research Database (Denmark)

Mogensen, Stine; Sverrisdóttir, Eva; Sveinsdóttir, Kolbrún

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...... 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....

Single Oral Dose Toxicity Test of Blue Honeysuckle Concentrate in Mice

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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

Split high‐dose oral levothyroxine treatment as a successful therapy option in myxedema coma

OpenAIRE

Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

2017-01-01

Key Clinical Message High‐dose intravenous thyroxine (T4) is the preferable treatment for myxedema coma. We describe the clinical course of a 69‐year‐old man who presented with myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split dose. This suggests split high‐dose oral LT4 as a therapeutic option in myxedema coma.

Pharmacokinetics of morphine-6-glucuronide following oral administration in healthy volunteers

DEFF Research Database (Denmark)

Villesen, Hanne H.; Kristensen, Kim; Hansen, Steen Honoré

2007-01-01

After oral administration, morphine-6-glucuronide (M6G) displays an atypical absorption profile with two peak plasma concentrations. A proposed explanation is that M6G is hydrolysed to morphine in the colon, which is then absorbed and subsequently undergoes metabolism in the liver to morphine-3-g......-glucuronide (M3G) and M6G. The aims of this study were to confirm and elucidate the biphasic absorption profile as well as clarify the conversion of M6G to morphine after a single oral administration of M6G in healthy volunteers....

Development of Alginate Microspheres Containing Chuanxiong for Oral Administration to Adult Zebrafish

Directory of Open Access Journals (Sweden)

Li-Jen Lin

2016-01-01

Full Text Available Oral administration of Traditional Chinese Medicine (TCM by patients is the common way to treat health problems. Zebrafish emerges as an excellent animal model for the pharmacology investigation. However, the oral delivery system of TCM in zebrafish has not been established so far. This issue was addressed by development of alginate microparticles for oral delivery of chuanxiong, a TCM that displays antifibrotic and antiproliferative effects on hepatocytes. The delivery microparticles were prepared from gelification of alginate containing various levels of chuanxiong. The chuanxiong-encapsulated alginate microparticles were characterized for their solubility, structure, encapsulation efficiency, the cargo release profile, and digestion in gastrointestinal tract of zebrafish. Encapsulation of chuanxiong resulted in more compact structure and the smaller size of microparticles. The release rate of chuanxiong increased for alginate microparticles carrying more chuanxiong in simulated intestinal fluid. This remarkable feature ensures the controlled release of encapsulated cargos in the gastrointestinal tract of zebrafish. Moreover, chuanxiong-loaded alginate microparticles were moved to the end of gastrointestinal tract after oral administration for 6 hr and excreted from the body after 16 hr. Therefore, our developed method for oral administration of TCM in zebrafish is useful for easy and rapid evaluation of the drug effect on disease.

High dose rate brachytherapy for oral cancer

International Nuclear Information System (INIS)

Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Koizumi, Masahiko; Ogawa, Kazuhiko; Furukawa, Souhei

2013-01-01

Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer. (author)

Effect of beam arrangement on oral cavity dose in external beam radiotherapy of nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Wu, Vincent W.C.; Yang Zhining; Zhang Wuzhe; Wu Lili; Lin Zhixiong

2012-01-01

This study compared the oral cavity dose between the routine 7-beam intensity-modulated radiotherapy (IMRT) beam arrangement and 2 other 7-beam IMRT with the conventional radiotherapy beam arrangements in the treatment of nasopharyngeal carcinoma (NPC). Ten NPC patients treated by the 7-beam routine IMRT technique (IMRT-7R) between April 2009 and June 2009 were recruited. Using the same computed tomography data, target information, and dose constraints for all the contoured structures, 2 IMRT plans with alternative beam arrangements (IMRT-7M and IMRT-7P) by avoiding the anterior facial beam and 1 conventional radiotherapy plan (CONRT) were computed using the Pinnacle treatment planning system. Dose-volume histograms were generated for the planning target volumes (PTVs) and oral cavity from which the dose parameters and the conformity index of the PTV were recorded for dosimetric comparisons among the plans with different beam arrangements. The dose distributions to the PTVs were similar among the 3 IMRT beam arrangements, whereas the differences were significant between IMRT-7R and CONRT plans. For the oral cavity dose, the 3 IMRT beam arrangements did not show significant difference. Compared with IMRT-7R, CONRT plan showed a significantly lower mean dose, V30 and V-40, whereas the V-60 was significantly higher. The 2 suggested alternative beam arrangements did not significantly reduce the oral cavity dose. The impact of varying the beam angles in IMRT of NPC did not give noticeable effect on the target and oral cavity. Compared with IMRT, the 2-D conventional radiotherapy irradiated a greater high-dose volume in the oral cavity.

Development of a simple and sensitive liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS) method for the determination of cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC) and its metabolites in rat whole blood after oral administration of a single high dose of CBD.

Science.gov (United States)

Palazzoli, Federica; Citti, Cinzia; Licata, Manuela; Vilella, Antonietta; Manca, Letizia; Zoli, Michele; Vandelli, Maria Angela; Forni, Flavio; Cannazza, Giuseppe

2018-02-20

The investigation of the possible conversion of cannabidiol (CBD) into Δ 9 -tetrahydrocannabinol (THC) in vivo after oral administration of CBD is reported herein since recent publications suggested a rapid conversion in simulated gastric fluid. To this end, single high dose of CBD (50mg/kg) was administered orally to rats and their blood was collected after 3 and 6h. A highly sensitive and selective LC-MS/MS method was developed and fully validated in compliance with the Scientific Working Group of Forensic Toxicology (SWGTOX) standard practices for method validation in forensic toxicology. This method also involved the optimization of cannabinoids and their metabolites extraction in order to remove co-eluting phospholipids and increase the sensitivity of the MS detection. Neither THC nor its metabolites were detected in rat whole blood after 3 or 6h from CBD administration. After oral administration, the amount of CBD dissolved in olive oil was higher than that absorbed from an ethanolic solution. This could be explained by the protection of lipid excipients towards CBD from acidic gastric juice. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Challenging the neuronal MIBG uptake by pharmacological intervention: effect of a single dose of oral amitriptyline on regional cardiac MIBG uptake

Energy Technology Data Exchange (ETDEWEB)

Estorch, Montserrat; Carrio, Ignasi; Mena, Esther; Flotats, Albert; Camacho, Valle; Fuertes, Jordi [Autonomous University of Barcelona, Department of Nuclear Medicine, Hospital Sant Pau, Barcelona (Spain); Kulisewsky, Jaume [Autonomous University of Barcelona, Department of Neurology, Hospital Sant Pau, Barcelona (Spain); Narula, Jagat [Irvine College of Medicine, Division of Cardiology, University of California, Irvine, CA (United States)

2004-12-01

Imaging with metaiodobenzylguanidine (MIBG) is used for the assessment of neuronal dysfunction in various cardiovascular disorders. Although valuable information is obtained by resting MIBG imaging, it is conceivable that competitive interference with the re-uptake mechanism would exaggerate MIBG defects and might unmask subclinical neuronal dysfunction. Tricyclic antidepressants, such as amitriptyline, have been reported to significantly increase cardiac MIBG washout and inhibit uptake into presynaptic neurons. This study was undertaken to assess whether a single oral dose of amitriptyline could influence cardiac MIBG distribution. Six patients (aged 62-81 years; four males, two females) who had demonstrated a normal cardiac MIBG scan during work-up for movement disorders were studied. The patients underwent a second {sup 123}I-MIBG study after oral administration of 25 mg amitriptyline within 1 week. Single-photon emission computed tomography images were acquired at 4 h to assess the regional distribution of MIBG, after generation of polar maps and employing a 20-segment model. Mean percentage of peak activity was calculated for each segment at rest and after amitriptyline administration. After amitriptyline administration, there was a decrease in regional MIBG uptake in 10{+-}4 segments per patient [62/120 segments (52%): 37 segments with a 5-10% decrease, 25 segments with a >10% decrease]. This change was statistically significant in lateral (P=0.003), apical (P<0.0001) and inferior (P=0.03) regions. A single oral dose of amitriptyline can induce changes in the uptake and retention of cardiac MIBG, indicating the feasibility of use of pharmacological intervention in cardiac neurotransmission imaging. (orig.)

[Directions for use of corticosteroids and calcineurin inhibitors against generalized myasthenia gravis: therapeutic strategies that can lead to early improvements and veer away from high-dose oral corticosteroids].

Science.gov (United States)

Utsugisawa, Kimiaki; Nagane, Yuriko; Suzuki, Shigeaki; Suzuki, Norihiro

2012-01-01

The advent of effective immune treatment has meant that myasthenia gravis (MG) is most often not lethal. However, many MG patients still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of medication, since full remission without immune treatment is not common. Our analysis demonstrated that disease severity, dose of oral corticosteroids, and depressive state are the major independent factors negatively associated with self-reported QOL (MG-QOL15-J score). It is noteworthy that oral corticosteroid, the first-line agent for MG, is negatively associated with patients' QOL. When the analysis took into account MGFA postintervention status and dose of oral prednisolne (PSL), the MG-QOL15-J score of MM status patients taking ≤ 5 mg PSL per day is identically low (i.e., just as good QOL) as that seen in CSR and is a target of treatment. In order to veer away from high-dose oral corticosteroids and to achieve early MM or better status with PSL ≤ 5 mg/day, we advocate the early aggressive treatment strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved clinical status using low-dose oral corticosteroids and calcineurin inhibitors (cyclosporine microemulsion and tacrolimus). The early stages of MG are susceptible to treatment with calcineurin inhibitors. When using cyclosporine microemulsion for MG, blood concentrations 2 h after administration (C2) correlate with clinical improvement and immediately before administration (C0) with side effects (increased serum creatinine and/or hypertension). Monitoring of C2 and C0 levels is useful to estimate efficacy and safety of the drug.

Single- and Multiple-Dose Study To Determine the Safety, Tolerability, Pharmacokinetics, and Food Effect of Oral MRX-I versus Linezolid in Healthy Adult Subjects.

Science.gov (United States)

Eckburg, Paul B; Ge, Yigong; Hafkin, Barry

2017-04-01

A multipart phase 1 study was conducted to determine the safety, tolerability, pharmacokinetics, and food effect of the novel oral oxazolidinone, MRX-I, in healthy adults, as well as the tolerability of longer-term exposure of both oral MRX-I and linezolid. Thirty subjects in part 1 received single ascending doses of MRX-I or placebo under fasting or fed condition in a double-blind crossover design. Twelve subjects in part 2 received MRX-I at 800 mg every 12 h (q12h) for 14 days in a double-blind, placebo-controlled design. In part 3, 24 subjects were randomized to receive 28 days of MRX-I at 800 mg q12h or oral linezolid at 600 mg q12h for 28 days in a double-blind, double-dummy design. Oral MRX-I was associated with a greater bioavailability and exposure when administered with food, and minimal accumulation of MRX-I occurred after multiple-dose administration. Oral MRX-I was well tolerated at single doses of up to 1,200 and 800 mg q12h for up to 28 days; all adverse events were mild to moderate in severity, and there was no drug discontinuation due to adverse events. These data support further clinical development of oral MRX-I in the treatment of resistant Gram-positive bacterial infections. Copyright © 2017 American Society for Microbiology.

Oral Administration of Shark Type II Collagen Suppresses Complete Freund’s Adjuvant-Induced Rheumatoid Arthritis in Rats

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Wenhui Wu

2012-03-01

Full Text Available Objective: Shark type II collagen (SCII is extracted as a glycoprotein from the cartilage of blue shark (Prionace glauca. We aim to confirm the effects of oral tolerance of SCII on inflammatory and immune responses to the ankle joint of rheumatoid-arthritis rats induced by Complete Freund’s Adjuvant (CFA. Materials and Methods: The onset of rheumatoid arthritis (RA was observed 14 ± x days after injection of CFA. Rats in the control group were treated with acetic acid by oral administration (0.05 mmol kg−1d−1, days 14–28, while rats in experimental groups were treated by oral administration with SCII (1 or 3 mg kg−1d−1, days 14–28, Tripterygium wilfordii polyglycosidium (TWP (10 mg kg−1d−1, days 14–28, and bovine type II collagen from US (US-CII (1 mg kg−1d−1, days 14–28, respectively. The severity of arthritis was evaluated by the articular swelling. The immunological indexes observed included delayed type hypersensitivity (DTH reaction, the level of interleukins 10 (IL-10 in rat blood serum and morphological characterization. Mixed lymphocyte culture (MLC was performed to investigate the relationship between T cell apoptosis and specific immune tolerance induced by SCII. Results: Treatment with SCII for 2 weeks significantly attenuated the acute inflammation. The rats orally administrated with SCII at the level of 3 mg kg−1d−1 (SCII 3 and US-CII had decreased DTH reaction compared with rats in control group. Rats treated with SCII 3 had the highest level of IL-10 with 102 pg/mL. SCII with concentration of 10 μg/L could help to significantly enhance level of Fas/Apo-1 in T cell in vitro. The result of histological staining indicated that the recovery of the articular membranes of ankle joint in SCII 3 group was greatly enhanced. Conclusions: Our results suggest that appropriate dose of SCII can not only ameliorate symptoms but also modify the disease process of Complete-Freunds-Adjuvant-induced arthritis. Oral

Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats.

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Kawaguchi, Shinichiro; Kuwahara, Rika; Kohara, Yumi; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

2015-02-01

Nonylphenol ethoxylate (NPE) is a non-ionic surfactant, that is degraded to short-chain NPE and 4-nonylphenol (NP) by bacteria in the environment. NP, one of the most common environmental endocrine disruptors, exhibits weak estrogen-like activity. In this study, we investigated whether oral administration of NP (at 0.5 and 5 mg/kg doses) affects spatial learning and memory, general activity, emotionality, and fear-motivated learning and memory in male and female Sprague-Dawley (SD) rats. SD rats of both sexes were evaluated using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) that was used to assess spatial learning and memory. In the MAZE test, the time required to reach the reward in male rats treated with 0.5 mg/kg NP group and female rats administered 5 mg/kg NP was significantly longer than that for control animals of the corresponding sex. In other behavioral tests, no significant differences were observed between the control group and either of the NP-treated groups of male rats. In female rats, inner and ambulation values for animals administered 0.5 mg/kg NP were significantly higher than those measured in control animals in open-field test, while the latency in the group treated with 5 mg/kg NP was significantly shorter compared to the control group in step-through passive avoidance test. This study indicates that oral administration of a low-dose of NP slightly impairs spatial learning and memory performance in male and female rats, and alters emotionality and fear-motivated learning and memory in female rats only.

Intraluminal Administration of Poly I:C Causes an Enteropathy That Is Exacerbated by Administration of Oral Dietary Antigen

Science.gov (United States)

Araya, Romina E.; Jury, Jennifer; Bondar, Constanza

2014-01-01

Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen. PMID:24915573

Bilateral femoral head avascular necrosis with a very low dose of oral corticosteroid used for panhypopituitarism.

Science.gov (United States)

Dharmshaktu, Pramila; Aggarwal, Anshita; Dutta, Deep; Kulshreshtha, Bindu

2016-01-13

Avascular necrosis (AVN) of the femoral head is a rare complication related to glucocorticoid administration and traditionally has been associated with high doses and/or prolonged therapy. Occurrence of osteonecrosis with a physiological replacement dose of glucocorticoids has not been reported previously. We report a 38-year-old man with non-secreting pituitary adenoma who developed bilateral AVN while on a very small dose of oral prednisolone for secondary adrenal insufficiency after surgery for pituitary adenoma. The patient was switched to hydrocortisone. Zolindronic acid was administered and the patient underwent bilateral core decompressive surgery resulting in a reduction of hip pain and improvement. When last evaluated, 2 years after diagnosis of AVN, the patient was functionally independent, and was able to do his routine activities with mild pain. The report intends to highlight the occurrence of AVN of the femur even with a very small dose of prednisolone used for treatment of panhypopituitarism. Glucocorticoids may have to be continued in the lowest possible dose using the most physiological preparation such as hydrocortisone when stoppage is not possible. 2016 BMJ Publishing Group Ltd.

Bilateral femoral head avascular necrosis with a very low dose of oral corticosteroid used for panhypopituitarism

Science.gov (United States)

Dharmshaktu, Pramila; Aggarwal, Anshita; Dutta, Deep; Kulshreshtha, Bindu

2016-01-01

Avascular necrosis (AVN) of the femoral head is a rare complication related to glucocorticoid administration and traditionally has been associated with high doses and/or prolonged therapy. Occurrence of osteonecrosis with a physiological replacement dose of glucocorticoids has not been reported previously. We report a 38-year-old man with non-secreting pituitary adenoma who developed bilateral AVN while on a very small dose of oral prednisolone for secondary adrenal insufficiency after surgery for pituitary adenoma. The patient was switched to hydrocortisone. Zolindronic acid was administered and the patient underwent bilateral core decompressive surgery resulting in a reduction of hip pain and improvement. When last evaluated, 2 years after diagnosis of AVN, the patient was functionally independent, and was able to do his routine activities with mild pain. The report intends to highlight the occurrence of AVN of the femur even with a very small dose of prednisolone used for treatment of panhypopituitarism. Glucocorticoids may have to be continued in the lowest possible dose using the most physiological preparation such as hydrocortisone when stoppage is not possible. PMID:26762348

Changes in Bioavailability of Omega-3 (DHA through Alpha-Tocopheryl Phosphate Mixture (TPM after Oral Administration in Rats

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Roksan Libinaki

2017-09-01

Full Text Available Benefits of Omega-3 Docosahexaenoic acid (DHA supplements are hindered by their poor solubility and bioavailability. This study investigated the bioavailability of various formulations of Omega-3 and tocopheryl phosphate mixture (TPM, following oral administration in rats, and assessed whether TPM could improve the oral absorption of DHA. The rats were administered with a high (265.7 mg/kg or low dose (88.6 mg/kg of DHA. TPM was examined at 1:0.1 w/w (low TPM dose and 1:0.5 w/w (high TPM dose. Over 24 h, the DHA plasma concentration followed a TPM dose-dependent relationship, reflected in the higher mean Cmax values (78.39 and 91.95 μg/mL and AUC values (1396.60 and 1560.60 for the low and high TPM, respectively. The biggest difference between the low dose DHA control (LDCont and TPM formulations was at 4 h after supplementation, where the low and high TPM showed a mean 20% (ns and 50% (p < 0.05 increase in DHA plasma concentrations versus the control formulation. After correcting for baseline endogenous DHA, the mean plasma DHA at 4 h produced by the LD-HTPM was nearly double (90% the LDC control (p = 0.057. This study demonstrated that co-administering omega-3 with TPM significantly increases the bioavailability of DHA in the plasma, suggesting potential use for commercially available TPM + DHA fortified products.

Inhibition of rat microsomal lipid peroxidation by the oral administration of D002

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Menéndez R.

2000-01-01

Full Text Available The effect of D002, a defined mixture of higher primary alcohols purified from bee wax, on in vivo and in vitro lipid peroxidation was studied. The extent of lipid peroxidation was measured on the basis of the levels of thiobarbituric acid reactive substances (TBARS. When D002 (5-100 mg/kg body weight was administered orally to rats for two weeks, a partial inhibition of the in vitro enzymatic and non-enzymatic lipid peroxidation was observed in liver and brain microsomes. Maximal protection (46% occurred at a dose of 25 mg/kg. D002 behaved differently depending on both the presence of NADPH and the integrity of liver microsomes, which suggests that under conditions where microsomal metabolism was favored the protective effect of D002 was increased. D002 (25 mg/kg also completely inhibited carbon tetrachloride- and toluene-induced in vivo lipid peroxidation in liver and brain. Also, D002 significantly lowered in a dose-dependent manner the basal level of TBARS in liver (19-40% and brain (28-44% microsomes. We conclude that the oral administration of D002 (5, 25 and 100 mg/kg for two weeks protected rat liver and brain microsomes against microsomal lipid peroxidation in vitro and in vivo. Thus, D002 could be useful as a dietary natural antioxidant supplement. More studies are required before these data can be extrapolated to the recommendation for the use of D002 as a dietary antioxidant supplement for humans.

Plasma methylphenidate concentrations in youths treated with high-dose osmotic release oral system formulation.

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Stevens, Jonathan R; George, Robert A; Fusillo, Steven; Stern, Theodore A; Wilens, Timothy E

2010-02-01

Children and adolescents are being treated increasingly for attention-deficit/hyperactivity disorder (ADHD) with a variety of stimulants in higher than Food and Drug Administration (FDA)-approved doses and in combination with other medications. We sought to determine methylphenidate (MPH) concentrations in children and adolescents treated with high-dose, extended-release osmotic release oral system (OROS) MPH plus concomitant medications, and to examine MPH concentrations with respect to the safety and tolerability of treatment. Plasma MPH concentrations were measured by liquid chromatography-mass spectrometry 4-5 hours after administration of medication in a sample of youths diagnosed with ADHD. These youths were treated naturalistically with higher than FDA-approved doses of OROS MPH in addition to their concomitant medications. Markers of safety and tolerability (e.g., measures of blood pressure and heart rate) were also examined. Among the 17 patients (with a mean age of 16.2 +/- 2 years and a mean number of concurrent medications of 2.23 +/- 0.94), the mean plasma MPH concentration was 28 +/- 9.1 ng/mL, despite a mean daily dose of OROS MPH of 169 +/- 5 mg (3.0 +/- 0.8 mg/kg per day). No patient had a plasma MPH level >or=50 ng/mL or clinical signs of stimulant toxicity. No correlation was found between plasma MPH concentrations and OROS MPH dose or changes in vital signs. High-dose OROS MPH, used in combination with other medications, was not associated with either unusually elevated plasma MPH concentrations or with clinically meaningful changes in vital signs. Study limitations include a single time-point sampling of MPH concentrations, a small sample size, and a lack of outcome measures to address treatment effectiveness.

Toxicologic evaluation of acute and subacute oral administration of Cucurbita maxima seed extracts to rats and swine.

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de Queiroz-Neto, A; Mataqueiro, M I; Santana, A E; Alessi, A C

1994-06-01

The extract prepared from dried seeds of Cucurbita maxima was administered to rats and pigs. Following a single dose or 4 weeks of daily oral administration, the extract produced no changes in serum glucose, urea, creatinine, total protein, uric acid, GOT, GPT, LDH or blood counts. Urine analysis (urea, uric acid, creatinine, total protein, Na and K), as well as histopathological investigation, showed no abnormalities. These results taken as a whole indicate that the seeds of C. maxima as used in Brazilian folk medicine are not toxic for rats and swine.

Oral administration of analgesia and anxiolysis for pain associated with bone marrow biopsy.

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Talamo, Giampaolo; Liao, Jason; Bayerl, Michael G; Claxton, David F; Zangari, Maurizio

2010-03-01

Medical literature provides only scarce data about the degree of pain experienced by patients undergoing a bone marrow aspiration and biopsy (BMAB), and little is known about the factors that can modify the perception of pain. In this study, we evaluated the effectiveness of a combination of analgesia and anxiolysis in reducing the pain score of patients undergoing BMAB. Eighty-four consecutive adult patients underwent BMAB after local anesthesia with 5 mL of lidocaine hydrochloride 1% aqueous solution in the left posterior superior iliac crest. Analgesia was obtained with acetaminophen 650 mg and oxycodone 10 mg, and anxiolysis was obtained with lorazepam 2 mg, all drugs given once orally 30 min before the procedure. We assessed the pain level with the Wong-Baker Faces Pain Rating Scale, which distinguishes six levels of pain, from 0 to 5. The 34 patients who received an oral administration of analgesia and anxiolysis reported pain at lower levels, i.e., in the range of 0-2, more frequently than the 50 patients who underwent BMAB without analgesia/anxiolysis (78% vs 64%, respectively). Among several predictors analyzed using a multivariate regression model, three were found to be associated with decreased pain level: the use of analgesia/anxiolysis, male sex, and increase in age (all with p values <0.05). Length of the extracted bone specimen, body mass index, and need of a spinal needle for anesthesia in obese patients did not predict for pain level. An oral administration of prophylactic regimen of analgesia and anxiolysis, at the above-mentioned doses, produced a statistically significant reduction of the perception of pain in patients undergoing BMAB, but its effect did not seem to provide a major and clinically significant reduction of pain level.

Oral fluid/plasma cannabinoid ratios following controlled oral THC and smoked cannabis administration.

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Lee, Dayong; Vandrey, Ryan; Milman, Garry; Bergamaschi, Mateus; Mendu, Damodara R; Murray, Jeannie A; Barnes, Allan J; Huestis, Marilyn A

2013-09-01

Oral fluid (OF) is a valuable biological alternative for clinical and forensic drug testing. Evaluating OF to plasma (OF/P) cannabinoid ratios provides important pharmacokinetic data on the disposition of drug and factors influencing partition between matrices. Eleven chronic cannabis smokers resided on a closed research unit for 51 days. There were four 5-day sessions of 0, 30, 60, and 120 mg oral ∆(9)-tetrahydrocannabinol (THC)/day followed by a five-puff smoked cannabis challenge on Day 5. Each session was separated by 9 days ad libitum cannabis smoking. OF and plasma specimens were analyzed for THC and metabolites. During ad libitum smoking, OF/P THC ratios were high (median, 6.1; range, 0.2-348.5) within 1 h after last smoking, decreasing to 0.1-20.7 (median, 2.1) by 13.0-17.1 h. OF/P THC ratios also decreased during 5-days oral THC dosing, and after the smoked cannabis challenge, median OF/P THC ratios decreased from 1.4 to 5.5 (0.04-245.6) at 0.25 h to 0.12 to 0.17 (0.04-5.1) at 10.5 h post-smoking. In other studies, longer exposure to more potent cannabis smoke and oromucosal cannabis spray was associated with increased OF/P THC peak ratios. Median OF/P 11-nor-9-carboxy-THC (THCCOOH) ratios were 0.3-2.5 (range, 0.1-14.7) ng/μg, much more consistent in various dosing conditions over time. OF/P THC, but not THCCOOH, ratios were significantly influenced by oral cavity contamination after smoking or oromucosal spray of cannabinoid products, followed by time-dependent decreases. Establishing relationships between OF and plasma cannabinoid concentrations is essential for making inferences of impairment or other clinical outcomes from OF concentrations.

Anti-tumour immune effect of oral administration of Lactobacillus

Indian Academy of Sciences (India)

Our results indicated that oral administration with L. plantarum inhibited CT26 cell ... (but not IL-4 or IL-17) production, and promotion of Th1-type CD4+ T differentiation. ... College of Animal Science and Technology, Jilin Agricultural University, ...

Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm).

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Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

2014-06-01

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats.

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Binkhathlan, Ziyad; Qamar, Wajhul; Ali, Raisuddin; Kfoury, Hala; Alghonaim, Mohammed

2017-09-01

Methoxy poly(ethylene oxide)- block -poly(ɛ-caprolactone) (PEO- b -PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO- b -PCL block copolymers and assess the toxic effects of drug-free PEO- b -PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO- b -PCL micelles, sixty animals were divided into two major groups: The first group received PEO- b -PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

Toxicity evaluation of methoxy poly(ethylene oxide-block-poly(ε-caprolactone polymeric micelles following multiple oral and intraperitoneal administration to rats

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Ziyad Binkhathlan

2017-09-01

Full Text Available Methoxy poly(ethylene oxide-block-poly(ɛ-caprolactone (PEO-b-PCL copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO-b-PCL block copolymers and assess the toxic effects of drug-free PEO-b-PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO-b-PCL micelles, sixty animals were divided into two major groups: The first group received PEO-b-PCL micelles (100 mg/kg by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

Renal, gastrointestinal, and hemostatic effects of oral administration of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis).

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Dijkstra, Bas; Guzman, David Sanchez-Migallon; Gustavsen, Kate; Owens, Sean D; Hass, Carlyle; Kass, Philip H; Paul-Murphy, Joanne R

2015-04-01

To investigate renal, gastrointestinal, and hemostatic effects associated with oral administration of multiple doses of meloxicam to healthy Hispaniolan Amazon parrots (Amazona ventralis). 12 Hispaniolan Amazon parrots. Birds were assigned to receive meloxicam oral suspension (1.6 mg/kg, PO, q 12 h) and 2.5 mL of tap water inserted into the crop by use of a gavage tube (n = 8) or the equivalent volume of tap water only (control group; 4) for 15 days. Urine and feces were collected 2 hours after treatment administration each day. Feces were evaluated for occult blood. Results of a CBC and serum biochemical analysis and measured N-acetyl-β-d-glucosaminidase (NAG) activity and whole blood clotting time were evaluated before, during, and after completion of treatments. Results of urinalysis and measured urine NAG activity were also evaluated. Birds treated with meloxicam had a significant increase in number of WBCs and decrease in PCV from before to after treatment. The PCV also decreased significantly, compared with results for the control group; however, WBC count and PCV for all birds remained within reference ranges throughout the study. One parrot treated with meloxicam had a single high value for urine NAG activity. Meloxicam administered orally at the dosage used in this study caused no apparent negative changes in several renal, gastrointestinal, or hemostatic variables in healthy Hispaniolan Amazon parrots. Additional studies to evaluate adverse effects of NSAIDs in birds will be needed.

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

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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.

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

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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.

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

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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.

A Study on the Single-dose Oral Toxicity of Super Key in Sprague-Dawley Rats

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Jinhee Kim

2015-09-01

Full Text Available Objectives: This study was performed to analyze the single-dose oral toxicity of the super key (processed sulfur. Methods: All experiments were conducted at Medvill, an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP regulations. In order to investigate the oral toxicity of super key We administered it orally to Sprague-Dawley (SD rats. The SD rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of super key 500 mg/kg, 1,000 mg/kg and 2,000 mg/kg were administered to the experimental groups, and a dose of normal saline solution, 10 mL/kg, was administered to the control group. We examined the survival rates, weights, clinical signs, gross findings and necropsy findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. (Approval number: A01-14018. Results: No deaths or abnormalities occurred in any of the four groups. Although slight decreases in the weights of some female rats were noted, no significant changes in weights or differences in the gross findings between the control group and the experimental groups were observed. To check for abnormalities in organs, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs. Conclusion: The results of this research showed that administration of 500 ─ 2,000 mg/kg of super key did not cause any changes in the weights or in the results of necropsy examinations. Neither did it result in any mortalities. The above findings suggest that treatment with super key is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

Detection and pharmacokinetics of grapiprant following oral administration to exercised Thoroughbred horses.

Science.gov (United States)

Knych, Heather K; Seminoff, Kelsey; McKemie, Dan S

2018-03-25

Traditional therapeutic options for the treatment of lameness associated with inflammation in performance horses include administration of cyclooxygenase enzyme inhibiting non-steroidal anti-inflammatory drugs (NSAID). As long-term use of these drugs can adversely impact the health of the horse, anti-inflammatories with a more favorable safety profile are warranted. Grapiprant is a newly approved non-cyclooxygenase inhibiting NSAID that has demonstrated efficacy and safety in other species and which may be a valuable alternative to traditional NSAIDs used in the horse. The objectives of the current study were to describe drug concentrations and the pharmacokinetics of grapiprant in exercised Thoroughbred horses and to develop an analytical method that could be used to regulate its use in performance horses. To that end, grapiprant, at a dose of 2 mg/kg was administered orally to 12 exercised Thoroughbred horses. Blood and urine samples were collected prior to and for up to 96 hours post drug administration. Drug concentrations were measured using liquid chromatography-tandem mass spectrometry. Grapiprant remained above the LOQ of the assay (0.005 ng/mL) in serum for 72 hours post administration and urine concentrations were above the LOQ until 96 hours. The C max , T max and elimination half-life were 31.9 ± 13.9 ng/mL, 1.5 ± 0.5 hours and 5.86 ± 2.46 hours, respectively. The drug was well tolerated in all horses at a dose of 2 mg/kg. Results support further study of this compound in horses. Furthermore, development of a highly sensitive analytical method demonstrate that this compound can be adequately regulated in performance horses. Copyright © 2018 John Wiley & Sons, Ltd.

The emergency contraceptive drug, levonorgestrel: a review of post-coital oral and peri-coital vaginal administration for prevention of pregnancy.

Science.gov (United States)

Sarkar, N N

2011-11-01

The objective of our study was the evaluation and elucidation of levonorgestrel (LNG) as emergency contraception (EC) administered through oral and vaginal routes. Data regarding post-coital oral and peri-coital vaginal application of LNG were extracted from the literature through MEDLINE database service for years 2001-2010. It was found that a single dose of 1.5 mg LNG or two doses of 0.75 mg LNG 12 h apart were used for EC. Currently, LNG is also on trial for vaginal application as EC in Carraguard gel for 'dual protection'. The oral or vaginal dose of 1.5 mg LNG resulted in peak plasma concentration, C(max) 19.2 or 3.21 ng/ml, with shorter time, T(max) 1.4 or 6.6 h, and greater AUC, 152.7 or 52.5 ng.h/ml, with shorter half-life, 25 or 32 h, respectively. LNG EC inhibited mid-cycle LH surge and delayed or prevented ovulation when administered before ovulation. Mechanism of action of LNG EC appeared to inhibit or delay ovulation. The risk of pregnancy was 4.12%. A single dose of 1.5 mg LNG could reduce the pregnancy rate to 0.7%. Occurrence of ectopic pregnancy following failure of LNG EC was reported. This EC caused no serious adverse effects but was associated with menstrual disturbance. Although widely acceptable, the cost and short-supply to rural areas pose a barrier to access EC for the poor and rural-dwellers, respectively. It was concluded that unlike post-coital oral administration, peri-coital vaginal application of 1.5 mg LNG needs further study to be an alternative option for women to use it for prevention of pregnancy.

Successful treatment for subinvolution of placental sites in the bitch with low oral doses of progestagen.

Science.gov (United States)

Voorhorst, M J; van Brederode, J C; Albers-Wolthers, C H J; de Gier, J; Schaefers-Okkens, A C

2013-10-01

Subinvolution of placental sites (SIPS) is the major cause of persistent sanguineous vaginal discharge after parturition in the bitch. Spontaneous remission is common but may take several months, and hence, medical therapy to end the discharge is often requested. In this retrospective study, we evaluated the effect of treatment for SIPS with low oral doses of a progestagen. Nine bitches with SIPS, but otherwise clinically healthy, were found in the computer database of the Department of Clinical Sciences of Companion Animals. Seven of these bitches were treated with low oral doses of a progestagen (megestrol acetate, 0.1 mg/kg body weight (bw) once daily for the 1st week, then 0.05 mg/kg bw once daily for the 2nd week). The other two bitches were untreated. Treatment results were evaluated by a telephone questionnaire. Progestagen treatment was successful in all of the treated dogs; sanguineous vaginal discharge stopped within the treatment period. One of the two untreated dogs remained symptomatic until the next oestrus, approximately 120 days after parturition, and the other remained symptomatic until 6 weeks before the start of the next pro-oestrus, 270 days after parturition. No side effects of the progestagen treatment were observed. Subsequent gestations, parturitions and puerperal periods of 5 mated bitches were uneventful. One bitch did not become pregnant after mating. In conclusion, the results of this study indicate that oral administration of low doses of progestagen for 2 weeks is effective in stopping persistent sanguineous vaginal discharge in bitches with SIPS, with neither side effects nor reduced subsequent fertility. © 2013 Blackwell Verlag GmbH.

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.

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

Directory of Open Access Journals (Sweden)

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.

Pharmacokinetics of dextromethorphan and its metabolites in horses following a single oral administration.

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Corado, Carley R; McKemie, Daniel S; Knych, Heather K

2017-06-01

Dextromethorphan is an N-methyl-D-aspartate (NMDA) non-competitive antagonist commonly used in human medicine as an antitussive. Dextromethorphan is metabolized in humans by cytochrome P450 2D6 into dextrorphan, which is reported to be more potent than the parent compound. The goal of this study is to describe the metabolism of and determine the pharmacokinetics of dextromethorphan and its major metabolites following oral administration to horses. A total of 23 horses received a single oral dose of 2 mg/kg. Blood samples were collected at time 0 and at various times up to 96 h post drug administration. Urine samples were collected from 12 horses up to 120 h post administration. Plasma and urine samples were analyzed using liquid chromatography-mass spectrometry, and the resulting data analyzed using non-compartmental analysis. The C max , T max , and the t 1/2 of dextromethorphan were 519.4 ng/mL, 0.55 h, and 12.4 h respectively. The area under the curve of dextromethorphan, free dextrorphan, and conjugated dextrorphan were 563.8, 2.19, and 6,691 h*ng/mL respectively. In addition to free and glucuronidated dextrorphan, several additional glucuronide metabolites were identified in plasma, including hydroxyl-desmethyl dextrorphan, desmethyl dextrorphan, and three forms of hydroxylated dextrorphan. Dextromethorphan was found to be eliminated from the urine predominately as the O-demethylated metabolite, dextrorphan. Several additional metabolites including several novel hydroxy-dextrorphan metabolites were also detected in the urine in both free and glucuronidated forms. No significant undesirable behavioural effects were noted throughout the duration of the study. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

[Purification of arsenic-binding proteins in hamster plasma after oral administration of arsenite].

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Wang, Wenwen; Zhang, Min; Li, Chunhui; Qin, Yingjie; Hua, Naranmandura

2013-01-01

To purify the arsenic-binding proteins (As-BP) in hamster plasma after a single oral administration of arsenite (iAs(III)). Arsenite was given to hamsters in a single dose. Three types of HPLC columns, size exclusion, gel filtration and anion exchange columns, combined with an inductively coupled argon plasma mass spectrometer (ICP MS) were used to purify the As-BP in hamster plasma. SDS-PAGE was used to confirm the arsenic-binding proteins at each purification step. The three-step purification process successfully separated As-BP from other proteins (ie, arsenic unbound proteins) in hamster plasma. The molecular mass of purified As-BP in plasma was approximately 40-50 kD on SDS-PAGE. The three-step purification method is a simple and fast approach to purify the As-BP in plasma samples.

Oral administration of prednisone to control refractory vertigo in Ménière's disease: a pilot study.

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Morales-Luckie, Elizabeth; Cornejo-Suarez, Arnulfo; Zaragoza-Contreras, Miguel A; Gonzalez-Perez, Oscar

2005-09-01

To establish whether the oral administration of moderate doses of prednisone reduces refractory vertigo in Ménière's disease. Blinded, randomized, controlled trial. Tertiary referral center. Patients with Ménière's disease with limited vertigo control (Class C) and severe disability (Scale 3). Two groups (n = 8 per group) were treated orally with either diphenidol (25 mg/d) plus acetazolamide (250 mg/48 h) (control group), or the same treatment plus prednisone (0.35 mg/kg) daily for 18 weeks (prednisone group). The variables evaluated were the frequency and duration of vertigo, tinnitus, aural fullness, and audiographic parameters. The clinical surveillance was performed for 12 months after prednisone withdrawal. The frequency and duration of vertigo episodes were reduced by 50% and 30%, respectively, by prednisone treatment. Prednisone-treated patients manifested a significant reduction in tinnitus. No changes were observed in aural fullness or hearing. No metabolic or infectious disorders were observed. Oral prednisone helps to control refractory vertigo in Ménière's disease. These preliminary data suggest that prednisone can be a good noninvasive antivertigo management regimen for these patients.

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

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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.

Evaluation of student nurses' perception of preparedness for oral medication administration in clinical practice: a collaborative study.

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Aggar, Christina; Dawson, Sonja

2014-06-01

Attainment of oral medication administration skills and competency for student nurses is challenging and medication errors are common. The ability of nurses to master a clinical skill is dependent upon educational instruction and practice. The aim of this study was to evaluate nursing students' perception of preparedness for oral medication administration in two practice environments and determine possible relationship between student demographics and their perceived preparedness for oral medication administration. This was a cross sectional, exploratory study. Eighty-eight second year students from a baccalaureate nursing course from two metropolitan Australian tertiary institutions participated. Student nurses' perception of preparedness for oral medication administration was measured via a self-administered, adapted, and validated questionnaire. The overall mean Total Preparedness Score was 86.2 (range 71-102). There was no significant difference for perceived total preparedness to administer oral medications between the two facilities. Whilst there was no significant relationship established between student demographics and their perceived preparedness to administer oral medications, four single questions related to clinical practice were shown to be significant. Low fidelity simulated teaching environments that incorporate time management and post medication situations, may improve student nurses' perceived preparedness for oral medication administration. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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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.

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

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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.

Relative bioavailability of single doses of prolonged-release tacrolimus administered as a suspension, orally or via a nasogastric tube, compared with intact capsules: a phase 1 study in healthy participants.

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Undre, Nasrullah; Dickinson, James

2017-04-04

Tacrolimus, an immunosuppressant widely used in solid organ transplantation, is available as a prolonged-release capsule for once-daily oral administration. In the immediate postsurgical period, if patients cannot take intact capsules orally, tacrolimus therapy is often initiated as a suspension of the capsule contents, delivered orally or via a nasogastric tube. This study evaluated the relative bioavailability of prolonged-release tacrolimus suspension versus intact capsules in healthy participants. A phase 1, open-label, single-dose, cross-over study. A single clinical research unit. In total, 20 male participants, 18-55 years old, entered and completed the study. All participants received nasogastric administration of tacrolimus 10 mg suspension in treatment period 1, with randomisation to oral administration of suspension or intact capsules in periods 2 and 3. Blood concentration-time profile over 144 hours was used to estimate pharmacokinetic parameters. Primary end point: relative bioavailability of prolonged-release intact capsule versus oral or nasogastric administration of prolonged-release tacrolimus suspension (area under the concentration-time curve (AUC) from time 0 to infinity post-tacrolimus dose (AUC 0-∞ ); AUC measured until the last quantifiable concentration (AUC 0-tz ); maximum observed concentration (C max ); time to C max (T max )). Tolerability was assessed throughout the study. Relative bioavailability of prolonged-release tacrolimus suspension administered orally was similar to intact capsules, with a ratio of least-square means for AUC 0-tz and AUC 0-∞ of 1.05 (90% CI 0.96 to 1.14). Bioavailability was lower with suspension administered via a nasogastric tube versus intact capsules (17%; ratio 0.83; CI 0.76 to 0.92). C max was higher for oral and nasogastric suspension (30% and 28%, respectively), and median T max was shorter (difference 1.0 and 1.5 hours postdose, respectively) versus intact capsules (2.0 hours). Single 10�

Effects of oral administration of titanium dioxide fine-sized particles on plasma glucose in mice.

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Gu, Ning; Hu, Hailong; Guo, Qian; Jin, Sanli; Wang, Changlin; Oh, Yuri; Feng, Yujie; Wu, Qiong

2015-12-01

Titanium dioxide (TiO2) is an authorized additive used as a food colorant, is composed of nano-sized particles (NP) and fine-sized particles (FP). Previous study reported that oral administration of TiO2 NPs triggers an increase in plasma glucose of mice. However, no previous studies have focused on toxic effects of TiO2 FPs on plasma glucose homeostasis following oral administration. In the current study, mice were orally administered TiO2 FPs greater than 100 nm in size (64 mg/kg body weight per day), and effects on plasma glucose levels examined. Our results showed that titanium levels was not changed in mouse blood, livers and pancreases after mice were orally administered TiO2 FPs. Biochemical analyzes showed that plasma glucose and ROS levels were not affected by TiO2 FPs. Histopathological results showed that TiO2 FPs did not induce pathology changes in organs, especially plasma glucose homeostasis regulation organs, such as pancreas and liver. Western blotting showed that oral administration of TiO2 FPs did not induce insulin resistance (IR) in mouse liver. These results showed that, TiO2 FPs cannot be absorbed via oral administration and affect plasma glucose levels in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives

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Giuseppe Benagiano

2009-04-01

Full Text Available Giuseppe Benagiano, Sabina Carrara, Valentina FilippiDepartment of Gynaecology and Obstetrics, Sapienza University, Rome, ItalyAbstract: The progestational steroid norgestrel was synthesized and tested between 1960 and 1965 through an international cooperation between Wyeth, USA and Schering, Berlin. It is a mixture of two “enantiomers,” with only one form (designated as levonorgestrel biologically active. When taken orally, it is rapidly absorbed, not subjected to a “first-pass” effect and is approximately 90% bioavailable, with a circulating half-life around 15 hours. Its contraceptive action is exerted at the central (hypothalamic and peripheral (cervical mucus and endometrium levels. Levonorgestrel (LNG, alone or in combination with ethinyl estradiol (EE, is the most widely employed contraceptive progestin: it is used in combined oral contraceptives, progestogen-only pills, long-acting contraceptive implants, intrauterine contraceptive systems and in emergency contraception. It is also the steroid of choice for new oral contraceptive regimens aimed at reducing the frequency of bleeding episodes. This novel approach, already tried more than 30 years ago, gained interest around the year 2000 when surveys of women’s attitudes toward monthly menstrual bleeding started to show a major change: more and more women declared that they would welcome a hormonal contraceptive method that reduced bleeding episodes to 4, 2 or even 1 per year. At this point, while the debate on the significance and “usefulness” of menstruation went on, attention focused on new regimens. The first new modality consisted of changing the 7-day medication-free interval, either shortening it to fewer than 7 days, or by the administration of low-dose estrogens during the interval between packages. Then, continuous administration regimens started to be investigated. This, however, did not happen suddenly, since, in specific situations, doctors had for years

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

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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

Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age.

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Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

2016-01-01

The objective of this report is describe the results of 2 studies that examined the pharmacokinetic parameters, safety profile, and tolerability of single and multiple ascending doses of oral delafloxacin and the effects of food, sex, and age on oral delafloxacin pharmacokinetic parameters, safety profile, and tolerability. The first study contained 3 parts and used unformulated delafloxacin in a capsule. Part 1 was a randomized, double-blind, placebo-controlled, single (50, 100, 200, 400, 800, 1200, and 1600 mg) ascending-dose study of oral delafloxacin in healthy men. Part 2 was a single-dose crossover study in which 20 men received 250 mg delafloxacin with or without food. Part 2 also included a parallel group, double-blind, placebo-controlled study in 16 women and 16 elderly men and women who were randomized (3:1) to receive 250 mg delafloxacin or placebo. Part 3 was a randomized, double-blind, placebo-controlled, multiple (100, 200, 400, 800, 1200 mg once daily for 5 days) ascending-dose study of oral delafloxacin in healthy men. The second study was a single-dose, randomized, 3-period crossover study in which participants received 900 mg delafloxacin (2 × 450-mg tablets) under fasted conditions, with a high-fat meal, or fasted with a high-fat meal 2 hours after dosing. Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were determined. Delafloxacin Cmax and AUC0-∞ increased with increasing oral dose over the dose range of 50 to 1600 mg. The increases in delafloxacin AUC0-∞ were dose proportional at doses of ≥200 mg. Steady state was reached by day 3 of dosing with minimal accumulation of delafloxacin. The Cmax of delafloxacin was decreased slightly in the presence of food. No sex difference in delafloxacin pharmacokinetic parameters was observed. In the elderly men and women, mean delafloxacin Cmax and AUC0-∞ were 35% higher than observed for young adults, which could be partially explained by a decrease in

Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

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Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju

2014-01-01

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions. PMID:25071922

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

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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

Bioavailability and Pharmacokinetics of Oral Cocaine in Humans.

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Coe, Marion A; Jufer Phipps, Rebecca A; Cone, Edward J; Walsh, Sharon L

2018-06-01

The pharmacokinetic profile of oral cocaine has not been fully characterized and prospective data on oral bioavailability are limited. A within-subject study was performed to characterize the bioavailability and pharmacokinetics of oral cocaine. Fourteen healthy inpatient participants (six males) with current histories of cocaine use were administered two oral doses (100 and 200 mg) and one intravenous (IV) dose (40 mg) of cocaine during three separate dosing sessions. Plasma samples were collected for up to 24 h after dosing and analyzed for cocaine and metabolites by gas chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by non-compartmental analysis, and a two-factor model was used to assess for dose and sex differences. The mean ± SEM oral cocaine bioavailability was 0.32 ± 0.04 after 100 and 0.45 ± 0.06 after 200 mg oral cocaine. Volume of distribution (Vd) and clearance (CL) were both greatest after 100 mg oral (Vd = 4.2 L/kg; CL = 116.2 mL/[min kg]) compared to 200 mg oral (Vd = 2.9 L/kg; CL = 87.5 mL/[min kg]) and 40 mg IV (Vd = 1.3 L/kg; CL = 32.7 mL/[min kg]). Oral cocaine area-under-thecurve (AUC) and peak concentration increased in a dose-related manner. AUC metabolite-to-parent ratios of benzoylecgonine and ecgonine methyl ester were significantly higher after oral compared to IV administration and highest after the lower oral dose. In addition, minor metabolites were detected in higher concentrations after oral compared to IV cocaine. Oral cocaine produced a pharmacokinetic profile different from IV cocaine, which appears as a rightward and downward shift in the concentration-time profile. Cocaine bioavailability values were similar to previous estimates. Oral cocaine also produced a unique metabolic profile, with greater concentrations of major and minor metabolites.

Oral administration of Allium sativum extract protects against infectious bursal disease in chickens

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Sufen ZHAO,Yuanyuan JIA,Weiwei ZHANG,Lili WANG,Yunfei MA,Kedao TENG

2015-12-01

Full Text Available Garlic (Allium sativum, Liliaceae has been safely used for more than 5000 years, and research on garlic extract is rapidly increasing because of its multiple biological functions. The in vivo effects of oral administration of garlic mixture (GM, water-soluble extract on infectious bursal disease virus (IBDV-infected specific pathogen free male white leghorn chicken were examined through histopathological, immunohistochemical, and Western blot analyses, and enzyme-linked immunosorbent assay. The results confirmed the protective effects of oral administration of 5 mg·kg-1 BW GM (Group GM1 on bursal lesions after IBDV infection. In particular, protein expression of IBDV in the bursa decreased in Group GM1, indicating that GM administration decreased IBDV replication in the bursa. Furthermore, immunoglobulin M- and A-bearing B lymphocytes significantly increased 7 days post infection in bursae in Group GM1 (P<0.01, suggesting that the oral administration of 5 mg·kg-1 GM offers moderate protection against B cell destruction after IBDV infection. During infection, the concentration of bursal interferon gamma (IFN-g increased and peaked in Group GM1 earlier than in Group T (IBDV-exposed, demonstrating that GM administration prompted the production of IFN-g to protect against IBDV infection.

Evaluation of crushed ticagrelor tablet doses: recovery following crushing and naso-gastric tube passage ex vivo.

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Crean, Barry; Finnie, Cindy; Crosby, Anna

2013-06-01

Orally available ticagrelor in combination with low-dose aspirin (75-100 mg/day) is indicated for adult patients with acute coronary syndromes. However, patients with swallowing difficulties may be unable to consume the currently available 90-mg tablet. It is hypothesized that ticagrelor could be given to this patient cohort as a crushed dose administered either orally or via a naso-gastric (NG) tube. To investigate the potential use of crushed ticagrelor tablets (90- and 180-mg doses) for oral dose or NG tube administration. Ticagrelor tablets (90 or 180 mg [two 90-mg tablets]) were prepared to emulate oral and NG tube administration by similar methods. For the oral dose, ticagrelor tablets were crushed using a mortar and pestle and transferred to a dosing cup. 100 mL of water was added to the mortar, stirred, and the contents were transferred to the dosing cup and stirred to form a suspension. At this stage, where the suspension would normally be administered to a patient, it was collected for high performance liquid chromatography (HPLC) analysis. The mortar was then flushed with 100 mL of water, and the contents were again transferred to the dosing cup, stirred, and collected for HPLC analysis. For the NG dose, polyvinylchloride, polyurethane, and silicone size CH10 NG tubes were used. The tablets were crushed using a mortar and pestle, diluted with 50 mL of water, and stirred. At this stage, where the suspension would normally be administered to a patient through an NG tube using a syringe, it was collected for HPLC analysis. The mortar was then flushed with two additional 50 mL aliquots of water and the contents were passed through the NG tube. HPLC analysis examined the recoverability of ticagrelor in each of the dose suspensions and flushes and the stability of the suspension when held in a syringe for up to 2 h. One or two crushed 90-mg ticagrelor tablets, prepared for either oral or NG tube administration, delivers a mean dose of ≥97% of the original

Pharmacokinetics of oxiracetam and its degraded substance (HOPAA after oral and intravenous administration in rats

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Xinhuan Wan

2014-12-01

Full Text Available The pharmacokinetics of oxiracetam and its degraded substance (4-hydroxy-2-oxo-1-pyrrolidine acetic acid, HOPAA after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method. Three groups of rats after an overnight fasted received 10 g/kg (n = 6 oxiracetam suspensions orally, and 2 g/kg (n = 6 normal or degraded oxiracetam injections intravenously via a caudal tail vein, respectively. Before the pharmacokinetic experiment, a simple safety evaluation test was conducted on the degraded oxiracetam injections containing 16.16% HOPAA in mice. There was no mortality by a single intravenous dose of 2 g/kg of degraded oxiracetam injections within two weeks, demonstrating that HOPAA was non-toxic in mice. Following intravenous administration of the normal injections, the plasma concentration-time curves of oxiracetam and HOPAA both showed a rapid elimination phase. The values of t1/2 were 3.1 ± 1.5 h for oxiracetam and 0.8 ± 0.2 h for HOPAA, and the mean residence times (MRT were 1.2 ± 0.1 h and 0.8 ± 0.1 h, respectively. Oxiracetam and HOPAA after intravenous administration of the degraded oxiracetam injections presented elimination patterns similar to those observed in the normal injections. Oral pharmacokinetic results showed that the Tmax was less than 1.5 h for the two analytes, and both had a longer t1/2 and MRT than those of intravenous administration. Contents of HOPAA in three groups were calculated based on AUC0–t values of the two analytes. The quantitative change of HOPAA in vivo was also evaluated by comparing the plasma concentrations of HOPAA and oxiracetam at the same time for every group. Additionally, the values of absolute bioavailability of oxiracetam were about 8.0% and 7.4% calculated by the normal or degraded oxiracetam injections, which were far less than the value of 75% reported in literature, indicating the necessity of further study.

Uracil-ftorafur: an oral fluoropyrimidine active in colorectal cancer.

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Sulkes, A; Benner, S E; Canetta, R M

1998-10-01

This review describes the early clinical development of uracil-ftorafur (UFT), an oral fluoropyrimidine, designed in 1978 by adding uracil to ftorafur. The review focuses on the treatment of colorectal cancer and summarizes the Japanese experience and the phase I and II trials performed in the United States and Europe. Clinical trials of UFT published in the Western world have included 581 patients with colorectal cancer. UFT has been administered in these trials as a single agent or biomodulated by leucovorin (LV). UFT was administered daily in split doses for periods that ranged from 14 to 28 days. The activity of oral UFT in large-bowel cancer when administered with oral LV (approximately 50 mg/dose) has resulted in objective response rates of approximately 40%. Response rates of approximately 25% (range, 17% to 39%) were reported when UFT was administered as a single agent or with lower doses of LV. The highest dose-intensities of UFT are achieved with 28-day schedules of administration. The maximum-tolerated dose (MTD) of UFT with this schedule, when administered concomitantly with oral LV 150 mg daily, is 300 mg/m2 daily. The dose-limiting toxicity (DLT) of UFT has generally been diarrhea. Other commonly described toxicities include nausea and vomiting, fatigue, and stomatitis. Myelosuppression occurs infrequently. Typically, hand-foot syndrome and neurologic toxicity are lacking. UFT is a fluoropyrimidine active in colorectal cancer. The oral route of administration and improved safety profile represent important advantages over both conventional and infusional fluorouracil (5-FU) regimens.

Pharmacokinetics and pharmacodynamics of d-chlorpheniramine following intravenous and oral administration in healthy Thoroughbred horses.

Science.gov (United States)

Kuroda, Taisuke; Nagata, Shun-ichi; Takizawa, Yoshimasa; Tamura, Norihisa; Kusano, Kanichi; Mizobe, Fumiaki; Hariu, Kazuhisa

2013-08-01

The pharmacokinetics of d-chlorpheniramine (CPM), a histamine H1-receptor antagonist, and its ability to inhibit of histamine-induced cutaneous wheal formation, were studied in healthy Thoroughbred horses (n=5). Following an intravenous (IV) dose of 0.5mg/kg bodyweight (BW), plasma drug disposition was very rapid, with the mean terminal half-life and total body clearance calculated as 2.7h and 0.7 L/h/kg, respectively. The observed maximal inhibition of wheal formation following IV doses of 0.1 and 0.5mg/kg BW were 37.8% and 60.6% at 0.5h, respectively. Oral administration of CPM (0.5mg/kg BW) resulted in a bioavailability of 38%, which induced a peak plasma drug concentration at 1h and a maximal inhibition of wheal formation (39%) at 2h. A pharmacokinetic/pharmacodynamic link model showed that CPM in horses has lower efficacy, much lower potency and slightly lower sensitivity than other reported antihistamines. These results indicated that CPM should be administered at frequent intervals or at large dose rates to maintain therapeutic concentrations in horses. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Reduced frequency of nickel allergy upon oral nickel contact at an early age

DEFF Research Database (Denmark)

Van Hoogstraten, I M; Andersen, Klaus Ejner; Von Blomberg, B M

1991-01-01

From animal studies we know that oral administration of T-dependent antigens before sensitization effectively induces systemic immune unresponsiveness. Such 'oral tolerance' is persistent, dose-dependent, antigen-specific and presumably T suppressor cell-mediated. Oral tolerance induction could b...

Absorption, distribution, metabolism and excretion of intravenously and orally administered tetrabromobisphenol A [2,3-dibromopropyl ether] in male Fischer-344 rats

International Nuclear Information System (INIS)

Knudsen, G.A.; Jacobs, L.M.; Kuester, R.K.; Sipes, I.G.

2007-01-01

Tetrabromobisphenol A bis[2,3-dibromopropyl ether],2,2-bis[3,5-dibromo-4-(2,3-dibromopropoxy)phenyl]propane is a brominated flame retardant with substantial U.S. production. Due to the likelihood of human exposure to TBBPA-DBPE and its probable metabolites, studies regarding the absorption, distribution, metabolism, and excretion were conducted. Male Fischer-344 rats were dosed with TBBPA-DBPE (20 mg/kg) by oral gavage or IV administration. Following a single oral administration of TBBPA-DBPE, elimination of [ 14 C] equivalents in the feces was extensive and rapid (95% of dose by 36 h). Following repeated daily oral doses for 5 or 10 days, route and rate of elimination was similar to single administrations of TBBPA-DBPE. After IV administration, fecal excretion of [ 14 C] equivalents was much slower (27% of dose eliminated by 36 h, 71% by 96 h). Urinary elimination was minimal ( 1/2β : 24.8 h; CL b : 0.1 mL min -1 . Kinetic constants following oral dosing were: t 1/2α : 2.5 h; t 1/2β : 13.9 h; CL b : 4.6 mL min -1 . Systemic bioavailability was 2.2%. Liver was the major site of disposition following oral or IV administration. After oral administration, 1% of the dose was eliminated in bile in 24 h (as metabolites). In in vitro experiments utilizing hepatocytes or liver microsomal protein, no detectable metabolism of TBBPA-DBPE occurred. These data indicate that TBBPA-DBPE is poorly absorbed from the gastrointestinal tract. Compound which is absorbed is sequestered in the liver, slowly metabolized, and eliminated in the feces

Radiation doses to the tissues of rat from tritiated thymidine administered by three different routes

International Nuclear Information System (INIS)

Takeda, Hiroshi; Iwakura, Tetsuo; Mabuchi, Yasuo.

1984-01-01

Biological behaviour of tritiated thymidine were investigated in rat over 120 days after oral, intraperitoneal or intravenous administration and the absorbed doses to different tissues were estimated. The result of present study revealed that the absorbed dose from tritiated thymidine varied with the route of administration. Among the three routes of administration, intraperitoneal injection gave the highest dose to all of the tissues examined. A significant difference due to the route of administration was found in spleen and small intestine, where the doses were, respectively, 3.3 and 4.5 times higher after intraperitoneal injection than after oral ingestion. The difference was substantially dependent on the dose value from non-volatile tritium which would be incorporated into DNA. Present observation suggests that the radiation hazards of tritiated thymidine differ depending on the route of entry into the body. (author)

Modification of pharmacokinetics of norfloxacin following oral administration of curcumin in rabbits

Science.gov (United States)

Pavithra, B. H.; Jayakumar, K.

2009-01-01

Investigation was carried out in adult New Zealand white rabbits to study the influence of curcumin pre-treatment on pharmacokinetic disposition of norfloxacin following single oral administration. Sixteen rabbits were divided into two groups of eight each consisting of either sex. Animals in group-I were administered norfloxacin (100 mg/kg body weight p.o), while animals in group-II received similar dose of norfloxacin after pre-treatment with curcumin (60 mg/kg body weight per day, 3 days, p.o). Blood samples were drawn from the marginal ear vein into heparin-coated vials at 0 (zero time), 5, 10, 15, 30 min and 1, 2, 4, 6, 12 and 24 h post-treatment. Plasma norfloxacin concentrations were determined by high performance liquid chromatography. The plasma concentration-time profile of norfloxacin was adequately described by a one-compartment open model. The pharmacokinetic data revealed that curcumin-treated animals had significantly (p ≤ 0.05) higher area under the plasma concentration-time curve and area under the first moment of plasma drug concentration-time curve. Prior treatment of curcumin significantly (p ≤ 0.05) increased elimination half-life and volume of distribution of norfloxacin. Further treatment with curcumin reduced loading and maintenance doses by 26% and 24% respectively. PMID:19934593

High dose rate versus low dose rate brachytherapy for oral cancer--a meta-analysis of clinical trials.

Directory of Open Access Journals (Sweden)

Zhenxing Liu

Full Text Available To compare the efficacy and safety of high dose rate (HDR and low dose rate (LDR brachytherapy in treating early-stage oral cancer.A systematic search of MEDLINE, EMBASE and Cochrane Library databases, restricted to English language up to June 1, 2012, was performed to identify potentially relevant studies.Only randomized controlled trials (RCT and controlled trials that compared HDR to LDR brachytherapy in treatment of early-stage oral cancer (stages I, II and III were of interest.Two investigators independently extracted data from retrieved studies and controversies were solved by discussion. Meta-analysis was performed using RevMan 5.1. One RCT and five controlled trials (607 patients: 447 for LDR and 160 for HDR met the inclusion criteria. The odds ratio showed no statistically significant difference between LDR group and HDR group in terms of local recurrence (OR = 1.12, CI 95% 0.62-2.01, overall mortality (OR = 1.01, CI 95% 0.61-1.66 and Grade 3/4 complications (OR = 0.86, CI 95% 0.52-1.42.This meta-analysis indicated that HDR brachytherapy was a comparable alternative to LDR brachytherapy in treatment of oral cancer. HDR brachytherapy might become a routine choice for early-stage oral cancer in the future.

Plasma levels of antiprogestin RU 486 following oral administration to non-pregnant and early pregnant women

International Nuclear Information System (INIS)

Swahn, M.L.; Wang, G.; Aedo, A.R.; Cekan, S.Z.; Bygdeman, M.

1986-01-01

RU 486 is a synthetic steroid which acts as an antiprogestin at the receptor level. The clinical usefulness of the compound for menstrual regulation and termination of early pregnancy is currently being evaluated. The aim of the present study was to determine the plasma levels of RU 486 following the oral administration of the compound to 42 pregnant and 10 non-pregnant women. The levels of RU 486 were measured by a radioimmunoassay method which uses chromatography on Sephadex LH 20 columns. The identity of the compound assayed as RU 486 was confirmed, but the presence of small amounts of two highly cross-reacting metabolites (monodemethyl and didemethyl RU 486) in the analyzed fractions could not be excluded. Following the ingestion of a single tablet containing 25 and 50 mg of the compound, a peak plasma value of approximately 3.5 to 4.0 mumol/l in both the pregnant and non-pregnant subjects was reached one to two hours later. The half-lives of elimination were about 20 hours in both the pregnant and the non-pregnant women. Following the repeated oral administration of 50, 100 or 200 mg of RU 486 daily for four days, maximum plasma levels of 2.9, 4.5 and 5.4 mumol/l, respectively, were found. Thus, the increase in plasma levels was not directly proportional to the increase in the dose. No accumulation of RU 486 in the plasma was found, even when the duration of treatment was prolonged to six days. The data partly explain the reported lack of relation between ingested dose and frequency of induced abortion and they may be useful for designing future studies on the use of compound to prevent implantation, induce menstruation or terminate an early pregnancy

Plasma levels of antiprogestin RU 486 following oral administration to non-pregnant and early pregnant women

Energy Technology Data Exchange (ETDEWEB)

Swahn, M.L.; Wang, G.; Aedo, A.R.; Cekan, S.Z.; Bygdeman, M.

1986-11-01

RU 486 is a synthetic steroid which acts as an antiprogestin at the receptor level. The clinical usefulness of the compound for menstrual regulation and termination of early pregnancy is currently being evaluated. The aim of the present study was to determine the plasma levels of RU 486 following the oral administration of the compound to 42 pregnant and 10 non-pregnant women. The levels of RU 486 were measured by a radioimmunoassay method which uses chromatography on Sephadex LH 20 columns. The identity of the compound assayed as RU 486 was confirmed, but the presence of small amounts of two highly cross-reacting metabolites (monodemethyl and didemethyl RU 486) in the analyzed fractions could not be excluded. Following the ingestion of a single tablet containing 25 and 50 mg of the compound, a peak plasma value of approximately 3.5 to 4.0 mumol/l in both the pregnant and non-pregnant subjects was reached one to two hours later. The half-lives of elimination were about 20 hours in both the pregnant and the non-pregnant women. Following the repeated oral administration of 50, 100 or 200 mg of RU 486 daily for four days, maximum plasma levels of 2.9, 4.5 and 5.4 mumol/l, respectively, were found. Thus, the increase in plasma levels was not directly proportional to the increase in the dose. No accumulation of RU 486 in the plasma was found, even when the duration of treatment was prolonged to six days. The data partly explain the reported lack of relation between ingested dose and frequency of induced abortion and they may be useful for designing future studies on the use of compound to prevent implantation, induce menstruation or terminate an early pregnancy.

Pharmacokinetics and dosimetry of the anti-androgen vinclozolin after oral administration inthe rat

Science.gov (United States)

Vinclozolin (V) is a fungicide with antiandrogenic properties. To determine the pharmacokinetics and dosimetry of V, adult male rats were administered an oral dose of V (100 mg/kg) in corn oil and sacrificed over time after dosing. V and its metabolites were analyzed in serum and...

Occlusion-amblyopia following high dose oral levodopa combined with part time patching

OpenAIRE

Mihir Kothari

2014-01-01

Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

Occlusion-amblyopia following high dose oral levodopa combined with part time patching.

Science.gov (United States)

Kothari, Mihir

2014-12-01

Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

20 CFR 416.1448 - Deciding a case without an oral hearing before an administrative law judge.

Science.gov (United States)

2010-04-01

... § 416.1448 Deciding a case without an oral hearing before an administrative law judge. (a) Decision... the decision is based. (b) Parties do not wish to appear. (1) The administrative law judge may decide... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Deciding a case without an oral hearing...

20 CFR 404.948 - Deciding a case without an oral hearing before an administrative law judge.

Science.gov (United States)

2010-04-01

....948 Deciding a case without an oral hearing before an administrative law judge. (a) Decision wholly... is based. (b) Parties do not wish to appear. (1) The administrative law judge may decide a case on... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Deciding a case without an oral hearing...

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�

Oral Administration of Pentoxifylline Reduces Endometriosis-Like Lesions in a Nude Mouse Model.

Science.gov (United States)

Perelló, Maria; González-Foruria, Iñaki; Castillo, Paola; Martínez-Florensa, Mario; Lozano, Francisco; Balasch, Juan; Carmona, Francisco

2017-06-01

Recent reports consider endometriosis to be an immunological disorder, thus suggesting potential efficacy of immunomodulators for its treatment. The aim of this study was to assess the effects of oral administration of pentoxifylline on endometriosis-like lesions in a heterologous mice model. Human endometrial tissue obtained from women (n = 5) undergoing surgery for benign conditions was implanted in nude female mice (n = 30). The animals were distributed into 3 experimental groups receiving: saline 0.1 mL/d (control, group 1); pentoxifylline 100 mg/kg/d (group 2), and pentoxifylline 200 mg/kg/d (group 3). After 28 days, the number of implants and the total volume of surgically extracted tissue were recorded. Immunohistochemical analysis was performed to assess the area of endometriosis and vascularization of endometriosis-like lesions. Cytokine levels in peritoneal fluid samples were measured. Macroscopic quantification showed a trend to dose-dependent reduction in the number of the endometriosis-like lesions after 28 days. The volume was significantly reduced in group 3 versus group 2 and controls (399.10 ± 120.68 mm 3 vs 276.75 ± 94.30 mm 3 and 145.33 ± 38.20 mm 3 , respectively; P = .04). Similarly, the mean area of endometriosis was significantly lower in group 3 (0.12 ± 0.08 mm 2 ) versus group 2 (1.35 ± 0.43 mm 2 ) and control (2.84 ± 0.60 mm 2 ; P = .001). Vascularization and cytokine levels were also reduced posttreatment. Our results suggest that the oral administration of pentoxifylline may be an alternative to current therapies for endometriosis. Nonetheless, further studies are required.

[Pharmacokinetics/pharmacodinamic (PK/PD) evaluation of a short course of oral administration of metronidazole for the management of infections caused by Bacteroides fragilis].

Science.gov (United States)

Morales-León, Felipe; von Plessing-Rossel, Carlos; Villa-Zapata, Lorenzo; Fernández-Rocca, Pola; Sanhueza-Sanhueza, Cindy; Bello-Toledo, Helia; Mella-Montecinos, Sergio

2015-04-01

Metronidazole is the antibiotic of choice for the management of infections caused by anaerobes. Its administration requires multiple daily doses causing increased medication errors. Due to its high post-antibiotic effect and rapid concentration-dependent bactericidal activity, administration of this antibiotic in an extended dosing interval would achieve PK/PD parameters effectively. To assess the probability of achieving effective PK/PD relationship with the administration of 1,000 mg every 24 hours of metronidazole for Bacteroides fragilis infections. A clinical trial was conducted in a group of volunteers who received a single oral dose of 500 or 1,000 mg of metronidazole. Determinations of values of Cmax, t max, and AUCC0-24 h. determined using the trapezoidal method, were obtained for a Markov simulation that would allow for determining the likelihood of achieving a AUC0-24 h/MIC ratio above 70 for infections caused by susceptible B. fragilis. Cmax (24,03 ± 6,89 mg/L) and t max (1,20 ± 0.80 hrs) and the value of AUC0-24 h (241.91 ± 48.14 mg * h/L) were determined. The probability of obtaining a AUC0-24 h/MIC ratio greater than 70 was greater than 99%. From a pharmacokinetic perspective, with the administration of a daily dose of 1,000 mg of metronidazole, it is possible to achieve a therapeutic goal of AUC0-24 h/MIC ratio above 70 for the treatment of anaerobic infections.

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

The antinociceptive effects of Monechma ciliatum and changes in EEG waves following oral and intrathecal administration in rats

Science.gov (United States)

Meraiyebu, Ajibola B.; Adelaiye, Alexander B.; O, Odeh S.

2010-02-01

The research work was carried out to study the effect of Oral and Intrathecal Monechma Ciliatum on antinociception and EEG readings in Wistar Rats. Traditionally the extract is given to women in labour believed to reduce pain and ease parturition, though past works show that it has oesteogenic and oxytotic effects. The rats were divided into 5 major groups. Group 1 served as oral control group while groups 2 and 3 served as oral experimental groups and were treated with 500mg/kg and 1000mg/kg monechma ciliatum respectively. Group 4 served as intrathecal control group treated with intrathecal dextrose and group 5 received 1000mg/kg Monechma Ciliatrum intrathecally. The antinociceptive effect was analysed using a Von Frey's aesthesiometer. Monechma Ciliatum showed significant antinociceptive effect both orally and intrathecally, although it had a greater effect orally and during the first 15 minutes of intrathecal administration. EEG readings were also taken for all the groups and there was a decrease in amplitude and an increase in frequency for high dose (1000mg/ml) experimental groups and the mid brain electrodes produced a change from theta waves (3.5 - 7 waves per second) to alpha waves (7.5 - 13 waves per second) as seen in relaxed persons and caused decreased amplitudes and change in distribution seen in beta waves. Properties similarly accentuated by sedativehypnotic drugs.

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

Science.gov (United States)

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

2016-01-01

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

Usefulness of low dose oral contrast media in FDG PET/CT

Energy Technology Data Exchange (ETDEWEB)

An, Y. S.; Yun, J. G.; Lee, M. H.; Cho, C. W.; Yun, S. N [Ajou University Medical Center, Suwon (Korea, Republic of)

2004-07-01

Oral contrast media might help in interpreting PET/CT images, allowing better discrimination between physiologic and pathologic abdominal uptake. The aim of this study was to evaluate the usefulness of low dose oral contrast on FDG PET/CT. A total of 435 cancer patients received 200mL of oral Barium with water(200mL) immediately before FDG injection. PET images were reconstructed using attenuation correction and iterative reconstruction. The FDG uptake in gastrointestinal(GI) tract were analyzed by visual and semiquantitative method in transaxial, coronal and sagittal planes. Seventy patients(16%, 113 sites) of 435 images showed high FDG uptake(pSUV>4.0) : 50(74%, 84 sites) with diffuse uptake and 20(26%, 29sites) with focal uptake. The most common distribution site of oral contrast media was small bowel (n=27, 39%) and others were small bowel with transverse colon(n=6, 8%), small bowel with ascending and sigmoid colon(n=6, 8%) and etc. In PET/CT images, FDG uptake coexisted with oral contrast was showed in 26 patients(54%) with diffuse pattern and 9(45%) with focal pattern, and by sites, those were 38(45%) and 9(31%), respectively. In small bowel regions, the most common distribution site, the proportion of coexistence reached as high as 61% (29 in the total 47 sites). Application of low dose contrast agent can be helpful in the evaluation of intestinal uptake in FDG PET/CT image.

Usefulness of low dose oral contrast media in FDG PET/CT

International Nuclear Information System (INIS)

An, Y. S.; Yun, J. G.; Lee, M. H.; Cho, C. W.; Yun, S. N

2004-01-01

Oral contrast media might help in interpreting PET/CT images, allowing better discrimination between physiologic and pathologic abdominal uptake. The aim of this study was to evaluate the usefulness of low dose oral contrast on FDG PET/CT. A total of 435 cancer patients received 200mL of oral Barium with water(200mL) immediately before FDG injection. PET images were reconstructed using attenuation correction and iterative reconstruction. The FDG uptake in gastrointestinal(GI) tract were analyzed by visual and semiquantitative method in transaxial, coronal and sagittal planes. Seventy patients(16%, 113 sites) of 435 images showed high FDG uptake(pSUV>4.0) : 50(74%, 84 sites) with diffuse uptake and 20(26%, 29sites) with focal uptake. The most common distribution site of oral contrast media was small bowel (n=27, 39%) and others were small bowel with transverse colon(n=6, 8%), small bowel with ascending and sigmoid colon(n=6, 8%) and etc. In PET/CT images, FDG uptake coexisted with oral contrast was showed in 26 patients(54%) with diffuse pattern and 9(45%) with focal pattern, and by sites, those were 38(45%) and 9(31%), respectively. In small bowel regions, the most common distribution site, the proportion of coexistence reached as high as 61% (29 in the total 47 sites). Application of low dose contrast agent can be helpful in the evaluation of intestinal uptake in FDG PET/CT image

Design and development of a lead jar for oral administration of radioiodine In hyperthyroid patients

International Nuclear Information System (INIS)

Rahman, M.S.; Paul, A.K.; Rahman, H.A.; Begum, F.

2005-01-01

Full text: Nuclear Medicine practices involve use of radioisotopes for diagnosis and treatment of diseases. Radioiodine is one of such radioisotopes, being used in the diagnosis and treatment of diseases since 1942. Handling of radioiodine involves radiation hazards both for the patients as well as for the technologists. Though radioiodine is supplied in a lead container, for treatment purpose, it is administered after dispensing into a glass jar that does not adequately protect radiation hazards. For this reason, we designed and developed a lead jar and radioiodine is dispensed into that lead jar to minimize radiation hazards. For oral administration of radioiodine to hyperthyroid patients, a lead jar was designed and developed with lead in Centre for Nuclear Medicine and Ultrasound, Khulna in December 2004 by own expertise and technologies in such a way that a glass jar could be introduced into that lead jar. The thickness of lead was 4.04 mm and the thickness of glass jar was 0.7 mm and thus the whole thickness of lead jar became 4.74 mm. The desired dose of radioiodine (8 mCi) that should be given to the patients were dispensed into that lead jar and administered orally to the patients. Radiation levels in 10 such cases were measured by Mini-Rad Series-1000 survey meter at 0.5 meter, 1 meter and 3 meters distances both lead jar and glass jar. The mean radiation level of lead jar and glass jar during oral administration of 8 mCi of Na 131 I solution in 10 cases at 0.5 meter, 1 meter and 3 meters distances were 62.4 ± 1.96 microSv/h, 17.7 ±1.95 microSv/h, 3.39 ± .12 microSv/h and 20.3± 2.16 microSv/h, 79.8 ± 0.79 microSv/h, 1.97 ± 0.23 microSv/h respectively. We have found that radiation level reduced by 67.47%, 61.58%, and 41.89% with lead jar at 0.5 meter, 1 meter and 3 meters distances. In conclusion, the locally designed and developed lead jar is safe, easy to handle and reduces radiation burden significantly in oral administration of radioiodine to

Occlusion-amblyopia following high dose oral levodopa combined with part time patching

Directory of Open Access Journals (Sweden)

Mihir Kothari

2014-01-01

Full Text Available Part time occlusion therapy is not reported to cause occlusion (reverse amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

Oral administration of Rauwolfia vomitoria extract has no untoward ...

African Journals Online (AJOL)

The effect of ethanolic extract of leaf and root of Rauwolfia vomitoria on kidney and liver functions in rats was investigated. Rats were given daily oral administration of ethanolic extracts of either root or leaf of R. vomitoria at two different concentrations (1.0 and 2.0 g/kg body weight) for a period of 14 days. Some biochemical ...

Results in patients treated with high-dose-rate interstitial brachytherapy for oral tongue cancer

International Nuclear Information System (INIS)

Yamamoto, Michinori; Shirane, Makoto; Ueda, Tsutomu; Miyahara, Nobuyuki

2006-01-01

Eight patients were treated with high-dose-rate interstitial brachytherapy for oral tongue cancer between September 2000 and August 2004. The patient distribution was 1 T1, 5 T2, 1 T3, and 1 T4a. Patients received 50-60 Gy in 10 fractions over seven days with high-dose-rate brachytherapy. Six of the eight patients were treated with a combination of external beam radiotherapy (20-30 Gy) and interstitial brachytherapy. The two-year primary local control rate was 83% for initial case. High-dose-rate brachytherapy was performed safely even for an aged person, and was a useful treatment modality for oral tongue cancer. (author)

Oral administration of heat-killed Lactobacillus gasseri OLL2809 reduces cedar pollen antigen-induced peritoneal eosinophilia in Mice.

Science.gov (United States)

Sashihara, Toshihiro; Ikegami, Shuji; Sueki, Natsuko; Yamaji, Taketo; Kino, Kohsuke; Taketomo, Naoki; Gotoh, Minoru; Okubo, Kimihiro

2008-12-01

Lactobacillus gasseri OLL2809 strongly stimulates the production of interleukin (IL)-12 (p70) by innate immune cells. Thus, it is expected to ameliorate allergic diseases. We investigated whether the oral administration of heat-killed L. gasseri OLL2809 suppressed eosinophilia in cedar pollen antigen-challenged mice. BALB/c mice sensitized with Japanese cedar pollen extract were intraperitoneally challenged with the same extract. The mice were orally given heat-killed L. gasseri OLL2809 at doses of 0.5, 1, or 2mg/day throughout the experimental period (21 d). After 24 hours of the challenge, the eosinophil number and cytokine levels in the peritoneal lavage fluid and the serum antigen-specific IgG levels were determined. On administering varying amounts of heat-killed L. gasseri OLL2809, the number of eosinophils among the total number of cells was significantly reduced in all groups. In addition, the eosinophil number significantly decreased, and the eosinophil-suppression rate significantly increased by 44% in the 2-mg group. Although the serum immunoglobulin (Ig) G2a and IgG1 levels were not affected, the IgG2a/IgG1 ratio increased significantly in the 2-mg group compared with that of the control group. Furthermore, the administration of heat-killed L. gasseri OLL2809 resulted in the induction of IL-2 and reduction in granulocyte-macrophage colony-stimulating factor levels in peritoneal lavage fluid. We demonstrated that the oral administration of heat-killed L. gasseri OLL2809 suppresses eosinophilia via the modulation of Th1/Th2 balance. These observations suggested that heat-killed L. gasseri OLL2809 might potentially ameliorate the increased number of eosinophils in patients with Japanese cedar pollinosis.

Effect of repeated administration of Damiana on selected kidney ...

African Journals Online (AJOL)

The effect of repeated oral administration of Damiana, an aphrodisiac, on selected renal function indices of male rats for 20 days was investigated. Male rats were orally administered with appropriate volume corresponding to human therapeutic dose of 3.6mg/kg body weight of diamiana at 24hour intervals. The effects on ...

Pharmacokinetics of Oral and Intravenous Paracetamol (Acetaminophen) When Co-Administered with Intravenous Morphine in Healthy Adult Subjects.

Science.gov (United States)

Raffa, Robert B; Pawasauskas, Jayne; Pergolizzi, Joseph V; Lu, Luke; Chen, Yin; Wu, Sutan; Jarrett, Brant; Fain, Randi; Hill, Lawrence; Devarakonda, Krishna

2018-03-01

Several features favor paracetamol (acetaminophen) administration by the intravenous rather than the oral route in the postoperative setting. This study compared the pharmacokinetics and bioavailability of oral and intravenous paracetamol when given with or without an opioid, morphine. In this randomized, single-blind, parallel, repeat-dose study in healthy adults, subjects received four repeat doses of oral or intravenous 1000 mg paracetamol at 6-h intervals, and morphine infusions (0.125 mg/kg) at the 2nd and 3rd intervals. Comparisons of plasma pharmacokinetic profiles were conducted before, during, and after opioid co-administrations. Twenty-two subjects were included in the pharmacokinetic analysis. Observed paracetamol peak concentration (C max ) and area under the plasma concentration-time curve over the dosing interval (AUC 0-6 ) were reduced when oral paracetamol was co-administered with morphine (reduced from 11.6 to 7.25 µg/mL and from 31.00 to 25.51 µg·h/mL, respectively), followed by an abruptly increased C max and AUC 0-6 upon discontinuation of morphine (to 13.5 µg/mL and 52.38 µg·h/mL, respectively). There was also a significantly prolonged mean time to peak plasma concentration (T max ) after the 4th dose of oral paracetamol (2.84 h) compared to the 1st dose (1.48 h). However, pharmacokinetic parameters of paracetamol were not impacted when intravenous paracetamol was co-administered with morphine. Morphine co-administration significantly impacted the pharmacokinetics of oral but not intravenous paracetamol. The abrupt release of accumulated paracetamol at the end of morphine-mediated gastrointestinal inhibition following oral but not intravenous administration of paracetamol suggests that intravenous paracetamol provides a better option for the management of postoperative pain. CLINICALTRIALS. NCT02848729.

Use of a monophasic, low dose oral contraceptive in relation to mental functioning

NARCIS (Netherlands)

Deijen, J.B.; Jansen, W.A.; Klitsie, J.; Duyn, K.

1992-01-01

The objective of the study was to evaluate the effect of Minulet, a new low-dose oral contraceptive on mood in two groups and to compare the effect with a control group of women not taking oral contraceptives (OC). The women participating were between 16 and 45 years of age. They completed the

Plant-based vaccines for oral delivery of type 1 diabetes-related autoantigens: Evaluating oral tolerance mechanisms and disease prevention in NOD mice.

Science.gov (United States)

Posgai, Amanda L; Wasserfall, Clive H; Kwon, Kwang-Chul; Daniell, Henry; Schatz, Desmond A; Atkinson, Mark A

2017-02-13

Autoantigen-specific immunological tolerance represents a central objective for prevention of type 1 diabetes (T1D). Previous studies demonstrated mucosal antigen administration results in expansion of Foxp3 + and LAP + regulatory T cells (Tregs), suggesting oral delivery of self-antigens might represent an effective means for modulating autoimmune disease. Early preclinical experiments using the non-obese diabetic (NOD) mouse model reported mucosal administration of T1D-related autoantigens [proinsulin or glutamic acid decarboxylase 65 (GAD)] delayed T1D onset, but published data are conflicting regarding dose, treatment duration, requirement for combinatorial agents, and extent of efficacy. Recently, dogma was challenged in a report demonstrating oral insulin does not prevent T1D in NOD mice, possibly due to antigen digestion prior to mucosal immune exposure. We used transplastomic plants expressing proinsulin and GAD to protect the autoantigens from degradation in an oral vaccine and tested the optimal combination, dose, and treatment duration for the prevention of T1D in NOD mice. Our data suggest oral autoantigen therapy alone does not effectively influence disease incidence or result in antigen-specific tolerance assessed by IL-10 measurement and Treg frequency. A more aggressive approach involving tolerogenic cytokine administration and/or lymphocyte depletion prior to oral antigen-specific immunotherapy will likely be required to impart durable therapeutic efficacy.

Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: a dose escalation and pharmacologic study.

Science.gov (United States)

Phuphanich, Surasak; Baker, Sharyn D; Grossman, Stuart A; Carson, Kathryn A; Gilbert, Mark R; Fisher, Joy D; Carducci, Michael A

2005-04-01

We determined the maximum tolerated dose (MTD), toxicity profile, pharmacokinetic parameters, and preliminary efficacy data of oral sodium phenylbutyrate (PB) in patients with recurrent malignant gliomas. Twenty-three patients with supratentorial recurrent malignant gliomas were enrolled on this dose escalation trial. Four dose levels of PB were studied: 9, 18, 27, and 36 g/day. Data were collected to assess toxicity, response, survival, and pharmacokinetics. All PB doses of 9, 18, and 27 g/day were well tolerated. At 36 g/day, two of four patients developed dose-limiting grade 3 fatigue and somnolence. At the MTD of 27 g/day, one of seven patients developed reversible grade 3 somnolence. Median survival from time of study entry was 5.4 months. One patient had a complete response for five years, and no partial responses were noted, which yielded an overall response rate of 5%. Plasma concentrations of 706, 818, 1225, and 1605 muM were achieved with doses of 9, 18, 27, and 36 g/day, respectively. The mean value for PB clearance in this patient population was 22 liters/h, which is significantly higher than the 16 liters/h reported in patients with other malignancies who were not receiving P450 enzyme-inducing anticonvulsant drugs (P = 0.038). This study defines the MTD and recommended phase 2 dose of PB at 27 g/day for heavily pretreated patients with recurrent gliomas. The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants.

Ability of Saudi mothers to appropriately and accurately use dosing devices to administer oral liquid medications to their children

Directory of Open Access Journals (Sweden)

Almazrou S

2014-12-01

Full Text Available Saja Almazrou, Hind Alsahly, Huda Alwattar, Lamya Alturki, Mona Alamri Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia Background: Most liquid medications are packaged with administration devices, which may be used inappropriately or inaccurately, and sometimes are not used at all. Because of the importance of their proper use for children's health, this study was designed to assess Saudi mothers' experiences with measuring cups, syringes, and droppers for oral liquid medications; to compare accuracy of dosing across these devices; and to determine the effects of mothers' education statuses and pharmacist counseling on dosing accuracy. Methods: This was a cross-sectional study in which mothers were observed as they used a set of commonly available dosing devices which are a dosing cup, syringe, and dropper. Interviews were conducted in the outpatient pharmacy waiting area in several tertiary hospitals and primary clinics in Riyadh, Saudi Arabia between March and April 2013. Saudi women who were mothers of children aged 12 years old or younger and who gave their consent were eligible. Caregivers other than mothers and subjects with vision problems or cognitive/physical disabilities were excluded. We gathered demographic information such as age, number of children, and education status. Subjects were asked if they had had counseling on how to use measuring devices and which device they preferred. Then, the mothers were required to demonstrate how to measure 5 mL of paracetamol (acetaminophen syrup using a cup and a syringe and 1 mL of paracetamol syrup using a dropper. Dosing errors were evaluated visually as overdosing, underdosing, or no error (if the dose was accurate. The data were entered into Microsoft Excel and evaluated using Stata 11.1. Logistic regression was employed to determine relationships. Results: The results revealed that 58% of participants measured an accurate dose of paracetamol

Methodological Study to Develop Standard Operational Protocol on Oral Drug Administration for Children.

Science.gov (United States)

Bijarania, Sunil Kumar; Saini, Sushma Kumari; Verma, Sanjay; Kaur, Sukhwinder

2017-05-01

To develop standard operational protocol (SOP) on oral drug administration and checklist to assess the implementation of the developed SOP. In this prospective methodological study, SOPs were developed in five phases. In the first phase, the preliminary draft of SOPs and checklists were prepared based on literature review, assessment of current practices and focus group discussion (FGD) with bedside working nurses. In the second phase, content validity was checked with the help of Delphi technique (12 experts). Total four drafts were prepared in stages and necessary modifications were made as per suggestions after each Delphi round. Fourth Delphi round was performed after conducting a pilot study. In the fourth phase, all bedside nurses were trained as per SOPs and asked to practice accordingly and observation of thirty oral drug administrations in children was done to check reliability of checklists for implementation of SOPs. In Phase-V, 7 FGDs were conducted with bedside nurses to assess the effectiveness of SOPs. The Content Validity Index (CVI) of SOP and checklists was 99.77%. Overall standardized Cronbach's alpha was calculated as 0.94. All the nurses felt that the SOP is useful. Valid and feasible SOP for drug administration to children through oral route along with valid and reliable checklist were developed. It is recommended to use this document for drug administration to children.

Single dose oral ranitidine improves MRCP image quality: a double-blind study

International Nuclear Information System (INIS)

Bowes, M.T.; Martin, D.F.; Melling, A.; Roberts, D.; Laasch, H.-U.; Sukumar, S.; Morris, J.

2007-01-01

Aim: To investigate the possibility of whether a single 300 mg dose of ranitidine given orally 2-3 h before magnetic resonance cholangiopancreatography (MRCP) could reduce the signal from the stomach and duodenum, and thus increase the conspicuousness of the biliary tree. Materials and methods: Thirty-five volunteers (22 female, 13 male), (age range 21-50) were underwent MRCP in a double-blind, placebo-controlled, randomized, crossover trial on a Philips Intera 1.5 T machine using a phased array surface coil. Imaging was carried out in the coronal oblique plane. Six 40 mm sections were acquired at varying angles to delineate the biliary tree and pancreatic duct. The 70 examinations were blindly scored by three consultants experienced in cholangiography. Results: After ranitidine administration there was a significant decrease in signal from the stomach (mean = 17.7, p = 0.0005, CI 10, 25.3) and duodenum (mean = 18.4, p = 0.0005, 95%CI 9.6, 27.1) with a significant increase in conspicuousness of the distal common duct (mean = 7.7, p = 0.033, 95%CI 0.7, 14.7) and proximal common duct (mean = 8.7, p = 0.010 CI 2.2, 15.2). There were no adverse effects. Conclusion: Oral ranitidine is a cheap and effective agent to decrease signal from the upper gastrointestinal tract and to improve visibility of the biliary tree

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.

Oral administration of the 5-HT6 receptor antagonists SB-357134 and SB-399885 improves memory formation in an autoshaping learning task.

Science.gov (United States)

Perez-García, Georgina; Meneses, Alfredo

2005-07-01

In this work we aimed to re-examine the 5-HT6 receptor role, by testing the selective antagonists SB-357134 (1-30 mg/kg p.o.) and SB-399885 (1-30 mg/kg p.o.) during memory consolidation of conditioned responses (CR%), in an autoshaping Pavlovian/instrumental learning task. Bioavailability, half-life and minimum effective dose to induce inappetence for SB-357134 were 65%, 3.4 h, and 30 mg/kg p.o., and for SB-399885 were 52%, 2.2 h, and 50 mg/kg p.o., respectively. Oral acute and chronic administration of either SB-357134 or SB-399885 improved memory consolidation compared to control groups. Acute administration of SB-357134, at 1, 3, 10 and 30 mg/kg, produced a CR% inverted-U curve, eliciting the latter dose a 7-fold increase relative to saline group. Acute injection of SB-399885 produced significant CR% increments, being 1 mg/kg the most effective dose. Repeated administration (7 days) of either SB-357134 (10 mg/kg) or SB-399885 (1 mg/kg) elicited the most significant CR% increments. Moreover, modeling the potential therapeutic benefits of 5-HT6 receptor blockade, acute or repeated administration of SB-399885, at 10 mg/kg reversed memory deficits produced by scopolamine or dizocilpine, and SB-357134 (3 and 10 mg/kg) prevented amnesia and even improved performance. These data support the notion that endogenously 5-HT acting, via 5-HT6 receptor, improves memory consolidation.

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

Oral transmucosal drug delivery for pediatric use.

Science.gov (United States)

Lam, Jenny K W; Xu, Yingying; Worsley, Alan; Wong, Ian C K

2014-06-01

The formulation of medicines for children remains a challenge. An ideal pediatric formulation must allow accurate dose administration and be in a dosage form that can be handled by the target age group. It is also important to consider the choices and the amount of excipients used in the formulation for this vulnerable age group. Although oral formulations are generally acceptable to most pediatric patients, they are not suitable for drugs with poor oral bioavailability or when a rapid clinical effect is required. In recent years, oral transmucosal delivery has emerged as an attractive route of administration for pediatric patients. With this route of administration, a drug is absorbed through the oral mucosa, therefore bypassing hepatic first pass metabolism and thus avoiding drug degradation or metabolism in the gastrointestinal tract. The high blood flow and relatively high permeability of the oral mucosa allow a quick onset of action to be achieved. It is a simple and non-invasive route of drug administration. However, there are several barriers that need to be overcome in the development of oral transmucosal products. This article aims to provide a comprehensive review of the current development of oral transmucosal delivery specifically for the pediatric population in order to achieve systemic drug delivery. The anatomical and physiological properties of the oral mucosa of infants and young children are carefully examined. The different dosage forms and formulation strategies that are suitable for young patients are discussed. © 2013.

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

Science.gov (United States)

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

2014-02-01

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

A Novel, Ecologically Relevant, Highly Preferred, and Non-invasive Means of Oral Substance Administration for Rodents

OpenAIRE

Sobolewski, Marissa; Allen, Joshua L.; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A.

2016-01-01

Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if ...

Metabolomic Analysis of Blood Plasma after Oral Administration of N-acetyl-d-Glucosamine in Dogs

Directory of Open Access Journals (Sweden)

Tomohiro Osaki

2015-08-01

Full Text Available N-acetyl-d-glucosamine (GlcNAc is a monosaccharide that polymerizes linearly through (1,4-β-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to examine amino acid metabolism after oral GlcNAc administration in dogs. Results showed that plasma levels of ectoine were significantly higher after oral administration of GlcNAc than prior to administration (p < 0.001. To our knowledge, there have been no reports of increased ectoine concentrations in the plasma. The mechanism by which GlcNAc administration leads to increased ectoine plasma concentration remains unclear; future studies are required to clarify this mechanism.

Low-dose oral tolerance due to antigen in the diet suppresses differentially the cholera toxin-adjuvantized IgE, IgA and IgG response

DEFF Research Database (Denmark)

Christensen, Hanne Risager; Kjær, Tanja; Frøkiær, Hanne

2003-01-01

Background: Cholera toxin (CT) is used as a mucosal adjuvant amongst other applications for studying food allergy because oral administration of antigen with CT induces an antigen-specific type 2 response, including IgE and IgA production. Priorly established oral tolerance due to antigen...... soy-trypsin inhibitor (KSTI) (F0 mice) and mice fed a soy-free diet (F2 mice) were orally immunized with KSTI and CT. KSTI-specific serum IgG1, IgG2a, IgA and IgE and fecal IgA were monitored. KSTI-stimulated cell proliferation and interleukin (IL)-6 production were determined. Results: The anti...... immunizations. However, cell proliferation and IL-6 production were clearly suppressed even after five immunizations. Conclusions: Priorly established low-dose oral tolerance considerably suppressed the CT-adjuvantized KSTI-specific IgE, IgA and cellular immune response but only weakly and transiently the Ig...

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.

Prehospital high-dose sublingual nitroglycerin rarely causes hypotension.

Science.gov (United States)

Clemency, Brian M; Thompson, Jeffrey J; Tundo, Gina N; Lindstrom, Heather A

2013-10-01

High-dose intravenous nitroglycerin is a common in-hospital treatment for respiratory distress due to congestive heart failure (CHF) with hypertension. Intravenous (IV) nitroglycerin administration is impractical in the prehospital setting. In 2011, a new regional Emergency Medical Services (EMS) protocol was introduced allowing advanced providers to treat CHF with high-dose oral nitroglycerin. The protocol calls for patients to be treated with two sublingual tabs (0.8 mg) when systolic blood pressure (SBP) was >160 mm Hg, or three sublingual tabs (1.2 mg) when SBP was >200 mm Hg, every five minutes as needed. Hypothesis/Problem To assess the protocol's safety, the incidence of hypotension following prehospital administration of multiple simultaneous nitroglycerin (MSN) tabs by EMS providers was studied. This study was a retrospective cohort study of patients from a single commercial EMS agency over a 6-month period. Records from patients with at least one administration of MSN were reviewed. For each administration, the first documented vital signs pre- and post-administration were compared. Administrations were excluded if pre- or post-administration vital signs were missing. One hundred case-patients had at least one MSN administration by an advanced provider during the study period. Twenty-five case-patients were excluded due to incomplete vital signs. Seventy-five case-patients with 95 individual MSN administrations were included for analysis. There were 65 administrations of two tabs, 29 administrations of three tabs, and one administration of four tabs. The mean change in SBP following MSN was -14.7 mm Hg (SD = 30.7; range, +59 to -132). Three administrations had documented systolic hypotension in the post-administration vital signs (97/71, 78/50 and 66/47). All three patients were over 65 years old, were administered two tabs, had documented improved respiratory status, and had repeat SBP of at least 100. The incidence of hypotension following MSN

Pharmacokinetic study of harmane and its 10 metabolites in rat after intravenous and oral administration by UPLC-ESI-MS/MS.

Science.gov (United States)

Li, Shuping; Teng, Liang; Liu, Wei; Cheng, Xuemei; Jiang, Bo; Wang, Zhengtao; Wang, Chang-Hong

2016-09-01

Context The β-carboline alkaloid harmane is widely distributed in common foods, beverages and hallucinogenic plants. Harmane exerts potential in therapies for Alzheimer's and depression diseases. However, little information on its dynamic metabolic profiles and pharmacokinetics in vivo is currently available. Objective This study investigates the dynamic metabolic profiles and pharmacokinetic properties of harmane and its metabolites in rats in vivo. Materials and methods A highly selective, sensitive and rapid ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed and well-validated for simultaneous quantitative determination of harmane and its uncertain endogenous metabolite harmine, as well as for semiquantitative determination of 10 harmane metabolites in rats after intravenous injection and oral administration of harmane at 1.0 and 30.0 mg/kg, respectively. Results The calibration curves of harmane and harmine showed excellent linearity within the concentration range of 1-2000 ng/mL with acceptable accuracy, precision, selectivity, recovery, matrix effect and stability. Ten metabolites, including harmane but not harmine, were detected and identified after intravenous and oral administration of harmane. The absolute bioavailability of harmane following an oral dose was 19.41 ± 3.97%. According to the AUC0-t values of all the metabolites, the metabolic levels of phase II metabolites were higher than those of phase I metabolites, and the sulphation pathways were the dominant metabolic routes for harmane in both routes of administration. Discussion and conclusion The pharmacokinetic properties of harmane and its 10 metabolites in rats were determined. Sulphate conjugation was the predominant metabolic process of harmane in rats.

The anti emetic effect of oral administration of ondansetron or granisetron in macacus cynomolgus exposed to mixed neutron-gamma irradiation; Effet antiemetique de l`ondansetron ou du granisetron administres oralement chez le macaque soumis a une irradiation mixte neutron-gamma

Energy Technology Data Exchange (ETDEWEB)

Martin, C.; Roman, V.; Martin, S.; Janodet, D.; Fatome, M. [Centre de Recherches du Service de Sante des Armees, 38 - La Tronche (France)

1995-10-01

Nausea and vomiting are the most often observed symptoms in the course of the early radiation syndrome. Their prevention has long been difficult because of the low effectiveness and side-effects of most antiemetics. There is a clear evidence that 5HT{sub 3} receptor antagonists such as ondansetron and granisetron are highly effective to prevent radiation-induced emesis without any side-effect. We studied the prophylactic effectiveness of their oral administration to macacus cynomolgus, for mixed neutron-gamma whole-body exposure, tat high dose rates. Doses of 4 mg of ondansetron or 1 mg of granisetron were administered before, or after, or both before and after irradiation. The treatment was effective when administered both before and after radiation exposure. It was significant but incomplete if administered once. Post-irradiation administration is interesting, particularly in case of accident. Both antiemetic drugs were well tolerated. Their effectiveness and tolerance are apparently comparable. The 5HT{sub 3} receptor antagonists represent a much improved treatment for radiation-induced nausea and vomiting by completely inhibiting emesis, if administered before and after irradiation. Unwanted sedation and extra-pyramidal side-effects, usually associated with the clinical use of D{sub 2} receptor antagonists, were not observed. (authors). 40 refs., 5 tabs.

Pharmacokinetic Evaluation of a Single Intramuscular High Dose versus an Oral Long-Term Supplementation of Cholecalciferol.

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Katharina Wylon

Full Text Available Vitamin D deficiency is frequent during the winter and occurs throughout the year in the elderly or patients suffering from autoimmune diseases. The objective of this study was to evaluate the pharmacokinetic properties of oral supplementation versus a single intramuscular injection of cholecalciferol in healthy individuals.Up to 8,000 I.U. oral cholecalciferol was administered daily for 84 days in a 4 week dose-escalation setting to vitamin D deficient individuals. In another cohort, a single intramuscular injection of 100,000 I.U. cholecalciferol was given. In both cohorts, individuals without vitamin D intake served as the comparison group. 25-hydroxyvitamin D (25(OHD concentrations were measured in all individuals at defined time points throughout the studies.The mean 25(OHD serum concentration increased significantly after oral cholecalciferol intake compared to the control group (day 28: 83.4 nmol/l and 42.5 nmol/l; day 56: 127.4 nmol/l and 37.3 nmol/l; day 84: 159.7 nmol/l and 30.0 nmol/l. In individuals receiving 100,000 I.U. cholecalciferol intramuscular, the mean 25(OHD serum concentration peaked after 4 weeks measuring 70.9 nmol/l compared to 32.7 nmol/l in the placebo group (p = 0.002. The increase of 25(OHD serum concentrations after 28 days was comparable between both routes of administration (p = 0.264.Oral and intramuscular cholecalciferol supplementation effectively increased serum 25(OHD concentrations.

A novel double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]tofogliflozin after oral administration and concomitant intravenous microdose administration of [13C]tofogliflozin in humans.

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Schwab, Dietmar; Portron, Agnes; Backholer, Zoe; Lausecker, Berthold; Kawashima, Kosuke

2013-06-01

Human mass balance studies and the assessment of absolute oral bioavailability (F) are usually assessed in separate studies. Intravenous microdose administration of an isotope tracer concomitant to an unlabeled oral dose is an emerging technique to assess F. We report a novel double-tracer approach implemented for tofogliflozin combining oral administration of a radiolabel tracer with concomitant intravenous administration of a stable isotope tracer. Tofogliflozin is a potent and selective sodium/glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus currently in clinical development. The objectives of the present study were to assess the systemic exposure of major circulating metabolites, excretion balance, F and contribution of renal clearance (CLR) to total clearance (CL) of tofogliflozin in healthy subjects within one study applying a novel double-tracer technique. Six healthy male subjects received 20 mg [(12)C/(14)C]tofogliflozin (3.73 MBq) orally and a concomitant microdose of 0.1 mg [(13)C]tofogliflozin intravenously. Pharmacokinetics of tofogliflozin were determined for the oral and intravenous route; the pharmacokinetics of the metabolites M1 and M5 were determined for the oral route. Quantification of [(12)C]tofogliflozin in plasma and urine and [(13)C]tofogliflozin in plasma was performed by selective LC-MS/MS methods. For the pre-selected metabolites of tofogliflozin, M1 and M5, a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to plasma and urine samples. Total radioactivity was assessed in plasma, urine and feces. Pharmacokinetic analysis was conducted by non-compartmental methods. The pharmacokinetics of tofogliflozin in healthy subjects were characterized by an F of 97.5 ± 12.3 %, CL of 10.0 ± 1.3 l/h and volume of distribution at steady-state (V(ss)) of 50.6 ± 6.7 l. The main route of elimination of total drug-related material was by excretion into urine (77.0 ± 4.1 % of the dose). The

Oral administration of curcumin suppresses production of matrix metalloproteinase (MMP)-1 and MMP-3 to ameliorate collagen-induced arthritis: inhibition of the PKCdelta/JNK/c-Jun pathway.

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Mun, Se Hwan; Kim, Hyuk Soon; Kim, Jie Wan; Ko, Na Young; Kim, Do Kyun; Lee, Beob Yi; Kim, Bokyung; Won, Hyung Sik; Shin, Hwa-Sup; Han, Jeung-Whan; Lee, Hoi Young; Kim, Young Mi; Choi, Wahn Soo

2009-09-01

We investigated whether oral administration of curcumin suppressed type II collagen-induced arthritis (CIA) in mice and its effect and mechanism on matrix metalloproteinase (MMP)-1 and MMP-3 production in CIA mice, RA fibroblast-like synoviocytes (FLS), and chondrocytes. CIA in mice was suppressed by oral administration of curcumin in a dose-dependent manner. Macroscopic observations were confirmed by histological examinations. Histological changes including infiltration of immune cells, synovial hyperplasia, cartilage destruction, and bone erosion in the hind paw sections were extensively suppressed by curcumin. The histological scores were consistent with clinical arthritis indexes. Production of MMP-1 and MMP-3 were inhibited by curcumin in CIA hind paw sections and tumor necrosis factor (TNF)-alpha-stimulated FLS and chondrocytes in a dose-dependent manner. As for the mechanism, curcumin inhibited activating phosphorylation of protein kinase Cdelta (PKCdelta) in CIA, FLS, and chondrocytes. Curcumin also suppressed the JNK and c-Jun activation in those cells. This study suggests that the suppression of MMP-1 and MMP-3 production by curcumin in CIA is mediated through the inhibition of PKCdelta and the JNK/c-Jun signaling pathway.

Oral fluid and plasma 3,4-methylenedioxymethamphetamine (MDMA) and metabolite correlation after controlled oral MDMA administration.

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Desrosiers, Nathalie A; Barnes, Allan J; Hartman, Rebecca L; Scheidweiler, Karl B; Kolbrich-Spargo, Erin A; Gorelick, David A; Goodwin, Robert S; Huestis, Marilyn A

2013-05-01

Oral fluid (OF) offers a noninvasive sample collection for drug testing. However, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) in OF has not been adequately characterized in comparison to plasma. We administered oral low-dose (1.0 mg/kg) and high-dose (1.6 mg/kg) MDMA to 26 participants and collected simultaneous OF and plasma specimens for up to 143 h after dosing. We compared OF/plasma (OF/P) ratios, time of initial detection (t first), maximal concentrations (C max), time of peak concentrations (t max), time of last detection (t last), clearance, and 3,4-methylenedioxyamphetamine (MDA)-to-MDMA ratios over time. For OF MDMA and MDA, C max was higher, t last was later, and clearance was slower compared to plasma. For OF MDA only, t first was later compared to plasma. Median (range) OF/P ratios were 5.6 (0.1-52.3) for MDMA and 3.7 (0.7-24.3) for MDA. OF and plasma concentrations were weakly but significantly correlated (MDMA: R(2) = 0.438, MDA: R(2) = 0.197, p MDMA low = 5.2 (0.1-40.4), high = 6.0 (0.4-52.3, p MDMA ratios in plasma were higher than those in OF (p MDMA ratios significantly increased over time in OF and plasma. The MDMA and MDA concentrations were higher in OF than in plasma. OF and plasma concentrations were correlated, but large inter-subject variability precludes the estimation of plasma concentrations from OF.

Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage

DEFF Research Database (Denmark)

Holm, C; Thomsen, L L; Norgaard, A

2017-01-01

BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open-label, ran......BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open...

Oral calcitonin

Directory of Open Access Journals (Sweden)

Hamdy RC

2012-09-01

meet key end points, and in December 2011, Novartis Pharma AG announced that it would not pursue further clinical development of oral calcitonin for postmenopausal osteoporosis or osteoarthritis. A unique feature of calcitonin is that it is able to uncouple bone turnover, reducing bone resorption without affecting bone formation and therefore increasing bone mass and improving bone quality. This effect, however, may be dose-dependent, with higher doses inhibiting both resorption and formation. Because so many factors affect the pharmacokinetics and pharmacodynamics of calcitonin, especially orally administered calcitonin, much work remains to be done to explore the full pharmacologic spectrum and potential of calcitonin and determine the optimum dose and timing of administration, as well as water and food intake.Keywords: oral calcitonin, osteoporosis, fractures, arthritis, pain

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

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

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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.

The Lack of Effect of Food on the Pharmacokinetics of ZX008 (Fenfluramine Oral Solution): Results of a Single-dose, Two-period Crossover Study.

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Gammaitoni, Arnold; Smith, Steven; Boyd, Brooks

2018-06-22

Fenfluramine is being developed as a low-dose adjunctive treatment for seizures in patients with Dravet syndrome and other epileptic encephalopathies, including Lennox-Gastaut syndrome. Most patients with Dravet syndrome receive multiple antiepileptic drugs, making it challenging for caregivers to track correct administration times. The present Phase I study was conducted to determine the effect of food on the pharmacokinetic properties of fenfluramine. Healthy nonsmoking subjects aged 18 to 50years were enrolled in an open-label, crossover, Phase I pharmacokinetic and safety profile study and received 2 single 0.8-mg/kg doses of ZX008 (fenfluramine hydrochloride oral solution), 1 after a 10-hour overnight fast and the other 30 minutes after the start of consumption of a high-fat breakfast, in a randomly assigned order. A washout period of at least 9days separated the 2 treatment periods. Venous blood samples were taken before each dose and periodically for 72hours after each dose for determination of concentrations of fenfluramine and its active metabolite norfenfluramine. Plasma pharmacokinetic parameters were estimated for each subject by noncompartmental analysis. In the 13 subjects completing both treatment periods, food had no effect on the rate or extent of absorption and bioavailability of fenfluramine as assessed by fed vs fasted adjusted geometric mean observed plasma C max (59.1vs 56.7 ng/mL; NS) and AUC 0-∞ (1640vs 1600 ng · h/mL; NS). Additionally, there was no impact of food on systemic exposure of norfenfluramine. Seven subjects reported at least 1 treatment-emergent adverse event; all treatment-emergent adverse events were mild in severity. The bioequivalence and tolerability of single 0.8-mg/kg oral doses of ZX008 in the fed and fasted states support ZX008 administration without regard to meals. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Nursing Administrators' Views on Oral Health in Long-Term Care Facilities: An exploratory study.

Science.gov (United States)

Urata, Janelle Y; Couch, Elizabeth T; Walsh, Margaret M; Rowe, Dorothy J

2018-04-01

Purpose: To explore the knowledge, attitudes, and practices of supervising nurse administrators (SNAs) regarding the oral care provided to long-term care facility (LTCF) residents and the role of dental professionals in those facilities. Methods: The investigators of this study partnered with the National Association of Nursing Administrators to send this cross-sectional study consisting of a 35-item electronic survey to its members whose email addresses were in their database. Online software tabulated responses and calculated frequencies (percentages) of responses for each survey item. Results: Of the 2,359 potential participants, 171 (n=171) completed the survey for a 7% response rate. Only 25% of the respondents were familiar with the expertise of dental hygienists (DHs), however once informed, the majority were interested in having DHs perform oral health staff trainings, oral screenings, and dental referrals and initiate fluoride varnish programs. Most respondents correctly answered the oral health-related knowledge items, understood that oral health is important to general health, but reported that the LTCF residents' oral health was only "good" or "fair." Fewer than half, (48%) of the SNAs were "very satisfied" with the quality of oral care provided to the residents. While more than half reported that they had no dentist on staff or on-site dental equipment, 77% reported that they would consider on-site mobile oral care services. Oral health training for staff was provided primarily by registered nurses, however only 32% reported including identification of dental caries as part of the in-service training. Conclusion: This exploratory study lays the foundation for more extensive research investigating various strategies to improve the oral health of LTCF residents, including increased collaboration between DHs and SNAs. Copyright © 2018 The American Dental Hygienists’ Association.

Effects of urine alkalization and activated charcoal on the pharmacokinetics of orally administered carprofen in dogs.

Science.gov (United States)

Raekallio, Marja R; Honkavaara, Juhana M; Säkkinen, Mia S; Peltoniemi, S Marikki

2007-04-01

To investigate the effects of oral administration of activated charcoal (AC) and urine alkalinization via oral administration of sodium bicarbonate on the pharmacokinetics of orally administered carprofen in dogs. 6 neutered male Beagles. Each dog underwent 3 experiments (6-week interval between experiments). The dogs received a single dose of carprofen (16 mg/kg) orally at the beginning of each experiment; after 30 minutes, sodium bicarbonate (40 mg/kg, PO), AC solution (2.5 g/kg, PO), or no other treatments were administered. Plasma concentrations of unchanged carprofen were determined via high-performance liquid chromatography at intervals until 48 hours after carprofen administration. Data were analyzed by use of a Student paired t test or Wilcoxon matched-pairs rank test. Compared with the control treatment, administration of AC decreased plasma carprofen concentrations (mean +/- SD maximum concentration was 85.9 +/- 11.9 mg/L and 58.1 +/- 17.6 mg/L, and area under the time-concentration curve was 960 +/- 233 mg/L x h and 373 +/- 133 mg/L x h after control and AC treatment, respectively). The elimination half-life remained constant. Administration of sodium bicarbonate had no effect on plasma drug concentrations. After oral administration of carprofen in dogs, administration of AC effectively decreased maximum plasma carprofen concentration, compared with the control treatment, probably by decreasing carprofen absorption. Results suggest that AC can be used to reduce systemic carprofen absorption in dogs receiving an overdose of carprofen. Oral administration of 1 dose of sodium bicarbonate had no apparent impact on carprofen kinetics in dogs.

Single oral dose toxicity test of platycodin d, a saponin from platycodin radix in mice.

Science.gov (United States)

Lee, Won-Ho; Gam, Cheol-Ou; Ku, Sae-Kwang; Choi, Seong-Hun

2011-12-01

The object of this study was to evaluate the single oral dose toxicity of platycodin D, a saponin from the root of Platycodon grandiflorum in male and female mice. Platycodin D was administered to female and male mice as an oral dose of 2000, 1000, 500, 250 and 125 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after treatment, upon necropsy, organ weight and histopathology of 14 principle organs were examined. As the results, no platycodin D treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2000 mg/kg in both female and male mice. Therefore, LD50 (50% lethal dose) and approximate LD of playtcodin D after single oral treatment in female and male mice were considered over 2000 mg/kg - the limited dosages recommended by KFDA Guidelines [2009-116, 2009], respectively.

Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: A dose escalation and pharmacologic study1

Science.gov (United States)

Phuphanich, Surasak; Baker, Sharyn D.; Grossman, Stuart A.; Carson, Kathryn A.; Gilbert, Mark R.; Fisher, Joy D.; Carducci, Michael A.

2005-01-01

We determined the maximum tolerated dose (MTD), toxicity profile, pharmacokinetic parameters, and preliminary efficacy data of oral sodium phenylbutyrate (PB) in patients with recurrent malignant gliomas. Twenty-three patients with supratentorial recurrent malignant gliomas were enrolled on this dose escalation trial. Four dose levels of PB were studied: 9, 18, 27, and 36 g/day. Data were collected to assess toxicity, response, survival, and pharmacokinetics. All PB doses of 9, 18, and 27 g/day were well tolerated. At 36 g/day, two of four patients developed dose-limiting grade 3 fatigue and somnolence. At the MTD of 27 g/day, one of seven patients developed reversible grade 3 somnolence. Median survival from time of study entry was 5.4 months. One patient had a complete response for five years, and no partial responses were noted, which yielded an overall response rate of 5%. Plasma concentrations of 706, 818, 1225, and 1605 μM were achieved with doses of 9, 18, 27, and 36 g/day, respectively. The mean value for PB clearance in this patient population was 22 liters/h, which is significantly higher than the 16 liters/h reported in patients with other malignancies who were not receiving P450 enzyme–inducing anticonvulsant drugs (P = 0.038). This study defines the MTD and recommended phase 2 dose of PB at 27 g/day for heavily pretreated patients with recurrent gliomas. The pharmacology of PB appears to be affected by concomitant administration of P450-inducing anticonvulsants. PMID:15831235

Labeling of red blood cells with Tc-99m after oral administration of SnCl2. Concise communication

International Nuclear Information System (INIS)

Patel, M.C.; Parab, P.B.; Samuel, A.M.; Ganatra, R.D.

1979-01-01

In vivo labeling of red blood cells with Tc-99m was possible after prior oral administration of SnCl 2 , both in rats and human volunteers. Absorption of oral SnCl 2 was low but sufficient for more than 95% labeling efficiency. Prior i.v. administration of stannous chloride is known to induce in vivo labeling of red blood cells with pertechnetate. We have observed that such labeling is possible even after oral administration of stannous chloide. Nearly 95% of the circulating radioactivity and 93.7% of the administered radioactivity was in RBCs 30 min after i.v. injection of /sup 99m/TcO 4 - in rats that were fed 5 mg of stannous chloride (3.13 mg Sn 2+ ion) 2 hr before injection. Red blood cells from four human volunteers could bind pertechnetate, both in vitro and in vivo, after oral administration of 100 mg of SnCl 2 . We have obtained a blood-pool image of the human heart by labeling the RBCs in vivo by this method. We have also studied various parameters affecting the in vivo binding of RBCs with Tc-99m - such as the amount of orally administered SnCl 2 , the time of injection of radionuclide after oral SnCl 2 , and the optimum time for the imaging

Detection of capecitabine (Xeloda®) on the skin surface after oral administration

Science.gov (United States)

Huang, Mao-Dong; Fuss, Harald; Lademann, Jürgen; Florek, Stefan; Patzelt, Alexa; Meinke, Martina C.; Jung, Sora

2016-04-01

Palmoplantar erythrodysesthesia (PPE), or hand-foot syndrome, is a cutaneous toxicity under various chemotherapeutics contributing to the most frequent side effects in patients treated with capecitabine (Xeloda®). The pathomechanism of PPE has been unclear. Here, the topical detection of capecitabine in the skin after oral application was shown in 10 patients receiving 2500 mg/m2/day capecitabine. Sweat samples were taken prior to and one week after oral administration of capecitabine. Using high-resolution continuum source absorption spectrometry, the changes in concentrations of fluorine, which is an ingredient of capecitabine, were quantified and statistically analyzed. Here, we show an increase in fluorine concentrations from 40±10 ppb (2±0.5 pM) before capecitabine administration to 27.7±11.8 ppm (14.6±6.5 nM) after application, ptoxic effect as a possible pathomechanism of PPE.

Iodine 131 therapy patients: radiation dose to staff

International Nuclear Information System (INIS)

Castronovo, F.P. Jr.; Beh, R.A.; Veilleux, N.M.

1986-01-01

Metastasis to the skeletal system from follicular thyroid carcinoma may be treated with an oral dose of 131 I-NaI. Radiation exposures to hospital personnel attending these patients were calculated as a function of administered dose, distance from the patient and time after administration. Routine or emergency patient handling tasks would not exceed occupational radiation protection guidelines for up to 30 min immediately after administration. The emergency handling of several patients presents the potential for exceeding these guidelines. (author)

Oral administration of a recombinant cholera toxin B subunit promotes mucosal healing in the colon.

Science.gov (United States)

Baldauf, K J; Royal, J M; Kouokam, J C; Haribabu, B; Jala, V R; Yaddanapudi, K; Hamorsky, K T; Dryden, G W; Matoba, N

2017-07-01

Cholera toxin B subunit (CTB) is a component of a licensed oral cholera vaccine. However, CTB has pleiotropic immunomodulatory effects whose impacts on the gut are not fully understood. Here, we found that oral administration in mice of a plant-made recombinant CTB (CTBp) significantly increased several immune cell populations in the colon lamina propria. Global gene expression analysis revealed that CTBp had more pronounced impacts on the colon than the small intestine, with significant activation of TGFβ-mediated pathways in the colon epithelium. The clinical relevance of CTBp-induced impacts on colonic mucosa was examined. In a human colon epithelial model using Caco2 cells, CTBp, but not the non-GM1-binding mutant G33D-CTBp, induced TGFβ-mediated wound healing. In a dextran sodium sulfate (DSS) acute colitis mouse model, oral administration of CTBp protected against colon mucosal damage as manifested by mitigated body weight loss, decreased histopathological scores, and blunted escalation of inflammatory cytokine levels while inducing wound healing-related genes. Furthermore, biweekly oral administration of CTBp significantly reduced disease severity and tumorigenesis in the azoxymethane/DSS model of ulcerative colitis and colon cancer. Altogether, these results demonstrate CTBp's ability to enhance mucosal healing in the colon, highlighting its potential application in ulcerative colitis therapy besides cholera vaccination.

Novel oral administrated paclitaxel micelles with enhanced bioavailability and antitumor efficacy for resistant breast cancer.

Science.gov (United States)

Zhang, Ting; Luo, Jingwen; Fu, Yao; Li, Hanmei; Ding, Rui; Gong, Tao; Zhang, Zhirong

2017-02-01

Paclitaxel (PTX) is a widely used antineoplastic drug in clinic. Due to poor aqueous solubility, it is administrated by intravenous infusion of cremophor EL containing formulation with serious adverse effects. The low oral bioavailability is a great challenge for oral formulation development. In addition, P-gp mediated multidrug resistance limit its clinical use in various resistant cancers. In this study, a novel super-antiresistant PTX micelle formulation for oral administration was developed. A P-gp inhibitor, bromotetrandrine (W198) was co-encapsulated in the micelle. The micelles were composed of Solutol HS 15 and d-a-tocopheryl polyethylene glycol succinate to avoid Cremophor EL induced toxicity. The micelles were round with a mean particle size of ∼13nm and an encapsulation efficiency of ∼90%. A series of in vitro evaluations were performed in non-resistant MCF-7 cells and resistant MCF-7/Adr cells. The super-antiresistant PTX micelles showed higher cell uptake efficiency, significantly increased cytotoxicity and antimitotic effect in drug resistant MCF-7/Adr cells when compared with Taxol and other PTX micelle formulations. Compared with Taxol, the super-antiresistant PTX micelles significantly improved bioavailability after oral administration in rats, and inhibited tumor growth in multidrug resistance xenografted MCF-7/Adr nude mice. In summary, the noval super-antiresistant PTX micelles showed a great potential for oral delivery of PTX against resistant breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of DA-8031, a novel oral compound for premature ejaculation, on male rat sexual behavior.

Science.gov (United States)

Kang, Kyung Koo; Sung, Ji Hyun; Kim, Soon Hoe; Lee, Sukhyang

2014-03-01

DA-8031 is a potent and selective serotonin transporter inhibitor developed for the treatment of premature ejaculation. The aim of the present study was to investigate the effects of DA-8031 on male sexual behavior in a rat model. Sexual behavior was examined after an acute oral administration of 10, 30 or 100 mg/kg of DA-8031 in copulation studies with female rats. Pharmacokinetic parameters were calculated after oral administration of DA-8031 at a dose level of 30 mg/kg. DA-8031 treatment produced a dose-dependent increase in ejaculation latency time and showed statistical significance at 30 and 100 mg/kg dosage levels compared with the vehicle (P DA-8031 treatment reduced the mean number of ejaculations in a dose-dependent manner. No changes in post-ejaculatory interval, numbers of mounts, intromissions or ejaculations were observed at any dose. In pharmacokinetic study, the blood concentration of DA-8031 peaked at 0.38 ± 0.14 h after oral administration, and then rapidly declined with a half-life of 1.79 ± 0.32 h. Treatment with DA-8031 delays the ejaculation latency time without affecting the initiation of mounting behavior or post-ejaculatory interval in rats. Furthermore, DA-8031 is rapidly absorbed and eliminated after oral administration in rats. These preclinical findings provide a clue for the clinical testing of DA-8031 as an "on-demand" agent for premature ejaculation. © 2013 The Japanese Urological Association.

Missed doses of oral antihyperglycemic medications in US adults with type 2 diabetes mellitus: prevalence and self-reported reasons.

Science.gov (United States)

Vietri, Jeffrey T; Wlodarczyk, Catherine S; Lorenzo, Rose; Rajpathak, Swapnil

2016-09-01

Adherence to antihyperglycemic medication is thought to be suboptimal, but the proportion of patients missing doses, the number of doses missed, and reasons for missing are not well described. This survey was conducted to estimate the prevalence of and reasons for missed doses of oral antihyperglycemic medications among US adults with type 2 diabetes mellitus, and to explore associations between missed doses and health outcomes. The study was a cross-sectional patient survey. Respondents were contacted via a commercial survey panel and completed an on-line questionnaire via the Internet. Respondents provided information about their use of oral antihyperglycemic medications including doses missed in the prior 4 weeks, personal characteristics, and health outcomes. Weights were calculated to project the prevalence to the US adult population with type 2 diabetes mellitus. Outcomes were compared according to number of doses missed in the past 4 weeks using bivariate statistics and generalized linear models. Approximately 30% of adult patients with type 2 diabetes mellitus reported missing or reducing ≥1 dose of oral antihyperglycemic medication in the prior 4 weeks. Accidental missing was more commonly reported than purposeful skipping, with forgetting the most commonly reported reason. The timing of missed doses suggested respondents had also forgotten about doses missed, so the prevalence of missed doses is likely higher than reported. Outcomes were poorer among those who reported missing three or more doses in the prior 4 weeks. A substantial number of US adults with type 2 diabetes mellitus miss doses of their oral antihyperglycemic medications.

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.

Metabolism, oral bioavailability and pharmacokinetics of chemopreventive kaempferol in rats

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Barve, Avantika; Chen, Chi; Hebbar, Vidya; Desiderio, Joseph; Saw, Constance Lay-Lay; Kong, Ah-Ng

2012-01-01

The purpose of this study was to compare the hepatic and small intestinal metabolism, and examine bioavailability and gastro-intestinal first-pass effects of Kaempferol in the rats. Liver and small intestinal microsomes fortified with either NADPH or UDPGA were incubated with varying concentrations of Kaempferol for upto 120 minutes. Based on the values of the kinetic constants (Km and Vmax), the propensity for UDPGA-dependent conjugation as compared to NADPH-dependent oxidative metabolism was higher for both hepatic and small intestinal microsomes. Male Sprague-Dawley rats were administered Kaempferol intravenously (IV) (10, 25 mg/kg) or orally (100, 250 mg/kg). Gastro-intestinal first pass effects were observed by collecting portal blood after oral administration of 100 mg/kg Kaempferol. Pharmacokinetic parameters were obtained by Noncompartmental analysis using WinNonlin. After IV administration, the plasma concentration-time profiles for 10 and 25 mg/kg were consistent with high clearance (~ 3 L/hr/kg) and large volumes of distribution (8-12 L/kg). The disposition was characterized by a terminal half-life value of 3-4 hours. After oral administration the plasma concentration-time profiles demonstrated fairly rapid absorption (tmax ~ 1-2 hours). The area under the curve (AUC) values after IV and oral doses increased proportional to the dose. The bioavailability (F) was poor at ~ 2%. Analysis of portal plasma after oral administration revealed low to moderate absorption. Taken together, the low F of Kaempferol is attributed in part to extensive first-pass metabolism by glucuronidation and other metabolic pathways in the gut and in the liver. PMID:19722166

Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

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Ana M. C. Faria

2006-01-01

Full Text Available Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10 and Th3 (TGF-β regulatory T cells (Tregs plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB, Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE, uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral, formulation, mucosal adjuvants, combination therapy and early therapy.

The effects of prolonged oral administration of the disinfectant calcium hypochlorite in Nigerian commercial cockerels

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Temitayo O. Iji

2013-11-01

Full Text Available This study was designed to investigate the effects of prolonged oral administration of calcium hypochlorite in the drinking water of commercial cockerels. It was carried out in order to ascertain probable toxicity associated with prolonged exposure to calcium hypochlorite. Thirty-two healthy birds were used; they were grouped into four groups of eight. Group 1, which served as the control, received 10 mL/kg body weight of physiological saline. Groups 2, 3 and 4 received 0.0375 g, 0.375 g and 0.75 g of calcium hypochlorite per 10 litres of drinking water for six weeks respectively. Six weeks after the administration of calcium hypochlorite, blood was collected from the jugular vein to assess liver function, lipid profiles and for markers of oxidative stress. The results revealed a significant (p < 0.05 increase in alanine aminotransferase activity in a dose-dependent manner when compared with the control. Also, there was a significant (p < 0.05 increase in aspartate aminotransferase and alkaline phosphatase activity. Similarly, there was a significant (p < 0.05 increase in total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein levels compared with the control. There was a significant increase in malondialdehyde and hydrogen peroxide generation with a concomitant significant (p < 0.05 decrease in serum glutathione level in a dose-dependent manner when compared with the control. In this study, calcium hypochloriteinduced hepatic damage via oxidative stress and decrease in antioxidant defense system was found. Therefore, prolonged exposure of chickens to calcium hypochlorite is potentially harmful.

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

DEFF Research Database (Denmark)

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

2015-01-01

OBJECTIVES: Cisplatin and vinorelbine given intravenously is a well-established adjuvant chemotherapy regimen after surgery for early-stage NSCLC. Vinorelbine can also be administered orally. However, the efficacy of orally administrated vinorelbine in adjuvant treatment of NSCLC is unknown. We...... University Hospital (Denmark) from 2005 to 2012 for adjuvant chemotherapy after surgery for NSCLC. RESULTS AND CONCLUSION: Of the 265 patients included in this study, 126 patients received i.v. and 139 received p.o. vinorelbine/cisplatin. The two groups were comparable with respect to important baseline....... In conclusion we observed that intravenous or oral administration of vinorelbine in combination with cisplatin after surgery for NSCLC appear equally effective in terms of overall and disease-free survival....

Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats

Science.gov (United States)

2014-01-01

Objective The aim of this study was to obtain kinetic data that can be used in human risk assessment of titanium dioxide nanomaterials. Methods Tissue distribution and blood kinetics of various titanium dioxide nanoparticles (NM-100, NM-101, NM-102, NM-103, and NM-104), which differ with respect to primary particle size, crystalline form and hydrophobicity, were investigated in rats up to 90 days post-exposure after oral and intravenous administration of a single or five repeated doses. Results For the oral study, liver, spleen and mesenteric lymph nodes were selected as target tissues for titanium (Ti) analysis. Ti-levels in liver and spleen were above the detection limit only in some rats. Titanium could be detected at low levels in mesenteric lymph nodes. These results indicate that some minor absorption occurs in the gastrointestinal tract, but to a very limited extent. Both after single and repeated intravenous (IV) exposure, titanium rapidly distributed from the systemic circulation to all tissues evaluated (i.e. liver, spleen, kidney, lung, heart, brain, thymus, reproductive organs). Liver was identified as the main target tissue, followed by spleen and lung. Total recovery (expressed as % of nominal dose) for all four tested nanomaterials measured 24 h after single or repeated exposure ranged from 64-95% or 59-108% for male or female animals, respectively. During the 90 days post-exposure period, some decrease in Ti-levels was observed (mainly for NM-100 and NM-102) with a maximum relative decrease of 26%. This was also confirmed by the results of the kinetic analysis which revealed that for each of the investigated tissues the half-lifes were considerable (range 28–650 days, depending on the TiO2-particle and tissue investigated). Minor differences in kinetic profile were observed between the various particles, though these could not be clearly related to differences in primary particle size or hydrophobicity. Some indications were observed for an

Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults.

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Gaskell, Helen; Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

2017-05-25

This review is an update of "Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults" last updated in Issue 4, 2009. Ketoprofen is a non-selective nonsteroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. This review is one of a series on oral analgesics for acute postoperative pain. Individual reviews have been brought together in two overviews to provide information about the relative efficacy and harm of the different interventions. To assess the efficacy and safety of single dose oral ketoprofen and oral dexketoprofen compared with placebo for acute postoperative pain, using methods that permit comparison with other analgesics evaluated in the same way, and criteria of efficacy recommended by an in-depth study at the individual patient level. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from 2009 to 28 March 2017. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries. Randomised, double-blind, placebo-controlled trials of single dose orally administered ketoprofen or dexketoprofen in adults with moderate to severe acute postoperative pain. Two review authors independently considered studies for inclusion in the review, examined issues of study quality and potential bias, and extracted data. For dichotomous outcomes, we calculated risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH) with 95% confidence intervals (CI) for ketoprofen and dexketoprofen, compared with placebo, where there were sufficient data. We collected information on the number of participants with at least 50

Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer

International Nuclear Information System (INIS)

Seong, Jinsil; Cho, Jae Ho; Kim, Nam Kyu; Min, Jin Sik; Suh, Chang Ok

2001-01-01

Purpose: The use of oral chemotherapeutic agents in chemoradiotherapy provides several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer. We attempted a Phase II trial of preoperative chemoradiotherapy with doxifluridine plus a low-dose oral leucovorin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated. Methods and Materials: There were 23 patients with primary unresectable rectal cancer in this trial, 21 of whom were available for analysis. The patients were treated with oral doxifluridine (900 mg/day) plus oral leucovorin (30 mg/day) from days 1 to 35, and pelvic radiation of 45 Gy over 5 weeks. Surgical resection was performed 5-6 weeks after the treatment. Results: Acute toxicity involved thrombocytopenia, nausea/vomiting, diarrhea, and skin reaction. All were in Grade 1/2, except diarrhea, which was not only the most frequent (7 patients, 33.3%), but also the only toxicity of Grade 3 (2 patients). The clinical tumor response was shown in 5 patients (23.8%) as a complete response and 13 patients (61.9%) as a partial response. A complete resection with negative resection margin was done in 18 patients (85.7%), in 2 of whom a pathologic complete response was shown (9.5%). The overall downstaging rate in the T- and N-stage groupings was 71.4% (15 patients). Conclusion: This study demonstrated the efficacy and low toxicity of chemoradiotherapy with doxifluridine. Currently, a Phase III randomized trial of chemoradiotherapy is ongoing at our institute to compare the therapeutic efficacy of oral 5-FU with respect to i.v. 5-FU in locally advanced and unresectable rectal cancer

Pharmacokinetics of dexmedetomidine combined with methadone following oral-transmucosal and intramuscular administration in dogs

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Federica Di Cesare

2017-05-01

Full Text Available Oral-transmucosal (OTM drug delivery refers to noninvasive and painless administration of medical preparations through any oral cavity membrane to achieve systemic effects (Sattar et al., 2014. Regarding sedative drugs, OTM administration is very attractive in veterinary medicine, especially for patients difficult to inject and restrain (Messenger et al., 2016. This study aims to compare the pharmacokinetics of dexmedetomidine after OTM and intramuscular (IM administration combined with methadone. After obtaining Ethical Committee approval and owner’s written consent, eight dogs, were administered with dexmedetomidine (10 mg/kg and methadone (0.4 mg/kg by OTM and other 4 dogs by IM route. Blood samples were collected at prefixed times up to four hours. Dexmedetomidine was quantified by a validated HPLC-MS method. On dexmedetomidine concentrations, a pharmacokinetic analysis was carried out with a noncompartmental approach (Phoenix WinNonlin® 7.0, Pharsight, Cary, NC. Mean ± SD terminal half-lives of dexmedetomidine were 187.42 ± 109.66 and 94.78 ± 34.08 min after OTM and IM administration, respectively. Maximum serum (Cmax concentrations were 0.83 ± 0.32 and 9.09 ± 2.46 ng/mL for OTM and IM administration, respectively. Time to maximum concentration (Tmax were 44.38 ± 32.16 and 21.25±11.39 min by OTM and IM administration, respectively. Area under the curve from 0 to the last measured concentration (AUClast were 103.75 ± 30.23 and 614.87 ± 77.15 min*ng/mL for OTM and IM administration, respectively. Cmax, Tmax and AUClast values by OTM route demonstrate a lower and delayed absorption of the drug compared to IM. To complete the study, the pharmacokinetic analysis of methadone is foreseen, so as a clinical trial to compare the clinical effects of the combination of dexmedetomidine and methadone by OTM and IM administration and to establish an effective dosage of oral-transumucosal route in dogs for this association.

Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration.

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Harigae, Takahiro; Nakagawa, Kiyotaka; Miyazawa, Taiki; Inoue, Nao; Kimura, Fumiko; Ikeda, Ikuo; Miyazawa, Teruo

2016-01-01

Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve the bioavailability of CUR, future

Pharmacokinetics of orally administered tramadol in domestic rabbits (Oryctolagus cuniculus).

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Souza, Marcy J; Greenacre, Cheryl B; Cox, Sherry K

2008-08-01

To determine the pharmacokinetics of an orally administered dose of tramadol in domestic rabbits (Oryctolagus cuniculus). 6 healthy adult sexually intact female New Zealand White rabbits. Physical examinations and plasma biochemical analyses were performed to ensure rabbits were healthy prior to the experiment. Rabbits were anesthetized with isoflurane, and IV catheters were placed in a medial saphenous or jugular vein for collection of blood samples. One blood sample was collected before treatment with tramadol. Rabbits were allowed to recover from anesthesia a minimum of 1 hour before treatment. Then, tramadol (11 mg/kg, PO) was administered once, and blood samples were collected at various time points up to 360 minutes after administration. Blood samples were analyzed with high-performance liquid chromatography to determine plasma concentrations of tramadol and its major metabolite (O-desmethyltramadol). No adverse effects were detected after oral administration of tramadol to rabbits. Mean +/- SD half-life of tramadol after administration was 145.4 +/- 81.0 minutes; mean +/- SD maximum plasma concentration was 135.3 +/- 89.1 ng/mL. Although the dose of tramadol required to provide analgesia in rabbits is unknown, the dose administered in the study reported here did not reach a plasma concentration of tramadol or O-desmethyltramadol that would provide sufficient analgesia in humans for clinically acceptable periods. Many factors may influence absorption of orally administered tramadol in rabbits.

Gut Microbiota-Regulated Pharmacokinetics of Berberine and Active Metabolites in Beagle Dogs After Oral Administration.

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Feng, Ru; Zhao, Zhen-Xiong; Ma, Shu-Rong; Guo, Fang; Wang, Yan; Jiang, Jian-Dong

2018-01-01

Berberine (BBR) is considered a multi-target drug that has significant advantages. In contrast to its significant pharmacological effects in clinic, the plasma level of BBR is very low. Our previous work revealed that dihydroberberine (dhBBR) could be an absorbable form of BBR in the intestine, and butyrate is an active metabolite that is generated by gut bacteria in rats. In this study, for the first time we describe gut microbiota-regulated pharmacokinetics in beagle dogs after oral administration of BBR by single (50 mg/kg) or multiple doses (50 mg/kg/d) for 7 days. GC-MS, GC, LC-MS/MS, and LC/MS n -IT-TOF were used to detect dhBBR, butyrate and BBR as well as its Phase I and II metabolites, respectively. The results showed that dhBBR was not detected in dog plasma but was excreted in small amounts in the feces of dogs examined on days 3 and 7. Butyrate was generated by gut bacteria and increased by 1.3- and 1.2-fold in plasma or feces, respectively, after 7 days of BBR treatment compared to the levels before treatment. Changes of intestinal bacterial composition were analyzed by 16S rRNA genes analysis. The results presented that dogs treated with BBR for 7 days increased both the abundance of the butyrate- and the nitroreductases- producing bacteria. We also identified chemical structures of the Phase I and II metabolites and analyzed their contents in beagle dogs. Eleven metabolites were detected in plasma and feces after BBR oral administration (50 mg/kg) to dogs, including 8 metabolites of Phase I and III metabolites of Phase II. The pharmacokinetic profile indicated that the concentration of BBR in plasma was low, with a C max value of 36.88 ± 23.45 ng/mL. The relative content of glucuronic acid conjugates (M11) was higher than those of other metabolites (M1, M2, M12, and M14) in plasma. BBR was detected in feces, with high excreted amounts on day 3 (2625.04 ± 1726.94 μg/g) and day 7 (2793.43 ± 488.10 μg/g). In summary, this is the first study to

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

Is oral absorption of vigabatrin carrier-mediated?

DEFF Research Database (Denmark)

Nøhr, M. K.; Juul, R. V.; Thale, Z. I.

2015-01-01

by mechanistic non-linear mixed effects modelling, evaluating PAT1-ligands as covariates on the PK parameters with a full covariate modelling approach. The oral absorption of vigabatrin was adequately described by a Michaelis-Menten type saturable absorption. Using a Michaelis constant of 32.8 mM, the model......-mediated and if the proton-coupled amino acid transporter 1 (PAT1) was involved in the absorption processes. Vigabatrin (0.3-300 mg/kg) was administered orally or intravenously to Sprague Dawley rats in the absence or presence of PAT1-ligands l-proline, l-tryptophan or sarcosine. The PK profiles of vigabatrin were described...... estimated a maximal oral absorption rate (Vmax) of 64.6 mmol/min and dose-dependent bioavailability with a maximum of 60.9%. Bioavailability was 58.5-60.8% at 0.3-30 mg/kg doses, but decreased to 46.8% at 300 mg/kg. Changes in oral vigabatrin PK after co-administration with PAT1-ligands was explained...

Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9

DEFF Research Database (Denmark)

Lidegaard, Øjvind; Nielsen, Lars Hougaard; Skovlund, Charlotte Wessel

2011-01-01

To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose.......To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose....

Efficacy of Single-Dose and Triple-Dose Albendazole and Mebendazole against Soil-Transmitted Helminths and Taenia spp.: A Randomized Controlled Trial

Science.gov (United States)

Steinmann, Peter; Utzinger, Jürg; Du, Zun-Wei; Jiang, Jin-Yong; Chen, Jia-Xu; Hattendorf, Jan; Zhou, Hui; Zhou, Xiao-Nong

2011-01-01

Background The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common STH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based randomized controlled trial in the People's Republic of China. Methodology/Principal findings The hookworm CR and fecal ERR were assessed in 314 individuals aged ≥5 years who submitted two stool samples before and 3–4 weeks after administration of single-dose oral albendazole (400 mg) or mebendazole (500 mg) or triple-dose albendazole (3×400 mg over 3 consecutive days) or mebendazole (3×500 mg over 3 consecutive days). Efficacy against T. trichiura, Ascaris lumbricoides, and Taenia spp. was also assessed. Albendazole cured significantly more hookworm infections than mebendazole in both treatment regimens (single dose: respective CRs 69% (95% confidence interval [CI]: 55–81%) and 29% (95% CI: 20–45%); triple dose: respective CRs 92% (95% CI: 81–98%) and 54% (95% CI: 46–71%)). ERRs followed the same pattern (single dose: 97% versus 84%; triple dose: 99.7% versus 96%). Triple-dose regimens outperformed single doses against T. trichiura; three doses of mebendazole – the most efficacious treatment tested – cured 71% (95% CI: 57–82%). Both single and triple doses of either drug were highly efficacious against A. lumbricoides (CR: 93–97%; ERR: all >99.9%). Triple dose regimens cured all Taenia spp. infections, whereas single dose applications cured only half of them. Conclusions/Significance Single-dose oral albendazole is more efficacious against hookworm than mebendazole. To achieve high CRs against both hookworm and T. trichiura, triple-dose regimens are

Usefulness of low dose oral contrast media in 18F-FDG PET/CT

International Nuclear Information System (INIS)

An, Young Sil; Yoon, Joon Kee; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam

2006-01-01

The standard protocol using large volume of oral contrast media may cause gastrointestinal discomfort and contrast-related artifacts in PET/CT. The aim of this study was to evaluate the usefulness of low dose oral contrast in 18 F-FDG PET/CT. We retrospectively reviewed the whole-body PET/CT images in a total of 435 patients. About 200 ml of oral contrast agent (barium sulfate) was administered immediately before injection of 18 F-FDG. The FDG uptake of intestines was analyzed by visual and semi-quantitative method on transaxial, coronal and saggital planes. Seventy (16%, 113 sites) of 435 images showed high FDG uptake (peak SUV > 4); 50 (74%, 84 sites) with diffuse and 20 (26%, 29 sites) with focal uptake. The most commonly delivered site of oral contrast media was small bowel (n = 27, 39%). On PET/CT images, FDG uptake coexisted with oral contrast media in 26 patients (54%, 38 sites) with diffuse pattern and 9 (45%, 9 sites) with focal pattern, and by sites, those were 38 (45%) and 9 (31%), respectively. In small bowel regions, the proportion of coexistence reached as high as 61% (29/47 sites). A visual analysis of available non-attenuation corrected PET images of 27 matched regions revealed no contrast-related artifact. We concluded that the application of low dose contrast media could be helpful in the evaluation of abdominal uptake in the FDG PET/CT image

A Phase 1 Pharmacokinetic Study of Cysteamine Bitartrate Delayed-Release Capsules Following Oral Administration with Orange Juice, Water, or Omeprazole in Cystinosis.

Science.gov (United States)

Armas, Danielle; Holt, Robert J; Confer, Nils F; Checani, Gregg C; Obaidi, Mohammad; Xie, Yuli; Brannagan, Meg

2018-02-01

Cystinosis is a rare, metabolic, autosomal recessive, genetic lysosomal storage disorder characterized by an accumulation of cystine in various organs and tissues. Cysteamine bitartrate (CB) is a cystine-depleting aminothiol agent approved in the United States and Europe in immediate-release and delayed-release (DR) formulations for the treatment of nephropathic cystinosis in children and adults. It is recommended that CBDR be administered with fruit juice (except grapefruit juice) for maximum absorption. Omeprazole is a proton pump inhibitor that inhibits gastric acid secretion and, theoretically, may cause the premature release of cysteamine by increasing intragastric pH, thereby affecting the PK of CBDR. This open-label, three-period, randomized study in healthy adult subjects was designed primarily to compare the pharmacokinetics of CBDR capsules after a single oral dose administered with orange juice, water, or multiple oral doses of omeprazole with water at steady state. A total of 32 subjects were randomly assigned to receive study agents in one of two treatment sequences. All subjects completed the study and baseline characteristics of the overall population and the two treatment sequence populations were similar. Peak mean plasma cysteamine concentrations following co-administration of CBDR capsules with orange juice (1892 ng/mL) were higher compared with co-administration with water (1663 ng/mL) or omeprazole 20 mg and water (1712 ng/mL). Mean time to peak plasma concentration was shorter with omeprazole co-administration (2.5 h) compared with orange juice (3.5 h) or water (3.0 h). Statistical comparisons between treatment groups indicated that exposure as assessed by AUC 0-t , AUC 0-∞ , and C max were all within the 80-125% bioequivalence ranges for all comparisons. All treatments were generally well tolerated. Overall, the pharmacokinetics of cysteamine bitartrate DR capsules are not significantly impacted by co-administration with orange juice

A preliminary 13-week oral toxicity study of ginger oil in male and female Wistar rats.

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Jeena, Kottarapat; Liju, Vijayastelter B; Kuttan, Ramadasan

2011-12-01

Zingiber officinale Roscoe, ginger, is a major spice extensively used in traditional medicine. The toxicity profile of ginger oil was studied by subchronic oral administration for 13 weeks at doses of 100, 250, and 500 mg/kg per day to 6 groups of Wistar rats (5/sex per dose). Separate groups of rats (5/sex per group) received either paraffin oil (vehicle) or were untreated and served as comparative control groups. There was no mortality and no decrease in body weight or food consumption as well as selective organ weights during the study period. Administration of ginger oil to rats did not produce any treatment-related changes in hematological parameters, hepatic, renal functions, serum electrolytes, or in histopathology of selected organs. The major component of ginger oil was found to be zingiberene (31.08%), and initial studies indicated the presence of zingiberene in the serum after oral dosing. These results confirmed that ginger oil is not toxic to male and female rats following subchronic oral administrations of up to 500 mg/kg per day (no observed adverse effect level [NOAEL]).

Errors detected in pediatric oral liquid medication doses prepared in an automated workflow management system.

Science.gov (United States)

Bledsoe, Sarah; Van Buskirk, Alex; Falconer, R James; Hollon, Andrew; Hoebing, Wendy; Jokic, Sladan

2018-02-01

The effectiveness of barcode-assisted medication preparation (BCMP) technology on detecting oral liquid dose preparation errors. From June 1, 2013, through May 31, 2014, a total of 178,344 oral doses were processed at Children's Mercy, a 301-bed pediatric hospital, through an automated workflow management system. Doses containing errors detected by the system's barcode scanning system or classified as rejected by the pharmacist were further reviewed. Errors intercepted by the barcode-scanning system were classified as (1) expired product, (2) incorrect drug, (3) incorrect concentration, and (4) technological error. Pharmacist-rejected doses were categorized into 6 categories based on the root cause of the preparation error: (1) expired product, (2) incorrect concentration, (3) incorrect drug, (4) incorrect volume, (5) preparation error, and (6) other. Of the 178,344 doses examined, 3,812 (2.1%) errors were detected by either the barcode-assisted scanning system (1.8%, n = 3,291) or a pharmacist (0.3%, n = 521). The 3,291 errors prevented by the barcode-assisted system were classified most commonly as technological error and incorrect drug, followed by incorrect concentration and expired product. Errors detected by pharmacists were also analyzed. These 521 errors were most often classified as incorrect volume, preparation error, expired product, other, incorrect drug, and incorrect concentration. BCMP technology detected errors in 1.8% of pediatric oral liquid medication doses prepared in an automated workflow management system, with errors being most commonly attributed to technological problems or incorrect drugs. Pharmacists rejected an additional 0.3% of studied doses. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Comparative study on the disposition of a new orally active dopamine prodrug, N-(N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine (TA-870) and dopamine hydrochloride in rats and dogs

International Nuclear Information System (INIS)

Yoshikawa, M.; Endo, H.; Otsuka, M.; Yamaguchi, I.; Harigaya, S.

1988-01-01

The pharmacokinetics of a dopamine derivative, TA-870, and dopamine (DA) after oral administration are compared in rats and dogs. The maximum concentrations of free DA in plasma after oral administration of TA-870 were 150 ng/ml in the rat (30 mg/kg) and 234 ng/ml in the dog (33.5 mg/kg). On the contrary, the maximum plasma concentrations after oral administration of DA at an equimolar dose to TA-870 were 12 ng/ml in the rat (12 mg/kg) and 36 ng/ml in the dog (13.5 mg/kg). The AUC values of free DA in plasma after oral administration of TA-870 (30 or 33.5 mg/kg) were 4-6 times higher than those after DA in both animal species. The peak tissue levels of radioactivity in rats after oral administration of [ 14 C]TA-870 (30 mg/kg) were also 5.5 times higher in the liver and 1-2 times higher in other tissues than those after [ 14 C]DA dose (12 mg/kg). In rats, the main excretion route of radioactivity after oral administration of [ 14 C]TA-870 or DA was via the urine. The total recoveries of radioactivity in the urine and feces were 91-96% of the dose within 24 hr for both compounds. Biliary excretion in rats accounted for 19.8% of the dose of [ 14 C]TA-870 and 12.6% of the dose of [ 14 C]DA within 24 hr. These results demonstrate that TA-870 was well absorbed from the digestive tract, extensively metabolized to dopamine, and proved to be an orally usable dopamine prodrug

Risk Factors and Dose-Effect Relationship for Mandibular Osteoradionecrosis in Oral and Oropharyngeal Cancer Patients

International Nuclear Information System (INIS)

Lee, Ik Jae; Koom, Woong Sub; Lee, Chang Geol; Kim, Yong Bae; Yoo, Sei Whan; Keum, Ki Chang; Kim, Gwi Eon; Choi, Eun Chang; Cha, In Ho

2009-01-01

Purpose: To analyze risk factors and the dose-effect relationship for osteoradionecrosis (ORN) of the mandible after radiotherapy of oral and oropharyngeal cancers. Materials and Methods: One-hundred ninety-eight patients with oral (45%) and oropharyngeal cancer (55%) who had received external radiotherapy between 1990 and 2000 were retrospectively reviewed. All patients had a dental evaluation before radiotherapy. The median radiation dose was 60 Gy (range, 16-75 Gy), and the median biologically effective dose for late effects (BED late ) in bone was 114 Gy 2 (range, 30-167 Gy 2 ). Results: The frequency of ORN was 13 patients (6.6%). Among patients with mandibular surgery, eight had ORN at the surgical site. Among patients without mandibular surgery, five patients had ORN on the molar area of the mandible. The median time to ORN was 22 months (range, 1-69 months). Univariate analysis revealed that mandibular surgery and Co-60 were significant risk factors for ORN (p = 0.01 and 0.04, respectively). In multivariate analysis, mandibular surgery was the most important factor (p = 0.001). High radiation doses over BED 102.6 Gy 2 (conventional dose of 54 Gy at 1.8 Gy/fraction) were also a significant factor for ORN (p = 0.008) and showed a positive dose-effect relationship in logistic regression (p = 0.04) for patients who had undergone mandibular surgery. Conclusions: Mandibular surgery was the most significant risk factor for ORN of mandible in oral and oropharyngeal cancers patients. A BED of 102.6 Gy 2 or higher to the mandible also significantly increases the risk of ORN.

Serum toxicokinetics after intravenous and oral dosing of larkspur toxins in goats

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Poisoning of cattle by larkspur plants (Delphinium spp.) is a concern for cattle ranchers in western North America. Previous research studies have evaluated the toxicokinetic profile of multiple larkspur toxins in several livestock species. However, those studies were all performed by orally dosing ...

Protection against bovine tuberculosis induced by oral vaccination of cattle with Mycobacterium bovis BCG is not enhanced by co-administration of mycobacterial protein vaccines.

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Wedlock, D Neil; Aldwell, Frank E; Vordermeier, H Martin; Hewinson, R Glyn; Buddle, Bryce M

2011-12-15

Mycobacterium bovis bacille Calmette-Guérin (BCG) delivered to calves by the oral route in a formulated lipid matrix has been previously shown to induce protection against bovine tuberculosis. A study was conducted in cattle to determine if a combination of a low dose of oral BCG and a protein vaccine could induce protective immunity to tuberculosis while not sensitising animals to tuberculin. Groups of calves (10 per group) were vaccinated by administering 2 × 10(7)colony forming units (CFU) of BCG orally or a combination of 2 × 10(7)CFU oral BCG and a protein vaccine comprised of M. bovis culture filtrate proteins (CFP) formulated with the adjuvants Chitin and Gel 01 and delivered by the intranasal route, or CFP formulated with Emulsigen and the TLR2 agonist Pam(3)CSK(4) and administered by the subcutaneous (s.c.) route. Two further groups were vaccinated with the CFP/Chitin/Gel 01 or CFP/Emulsigen/Pam(3)CSK(4) vaccines alone. Positive control groups were given 10(8)CFU oral BCG or 10(6)CFU s.c. BCG while a negative control group was non-vaccinated. All animals were challenged with M. bovis 15 weeks after vaccination and euthanized and necropsied at 16 weeks following challenge. Groups of cattle vaccinated with s.c. BCG, 10(8)CFU or 2 × 10(7)CFU oral BCG showed significant reductions in seven, three and four pathological or microbiological disease parameters, respectively, compared to the results for the non-vaccinated group. There was no evidence of protection in calves vaccinated with the combination of oral BCG and CFP/Emulsigen/Pam(3)CSK(4) or oral BCG and CFP/Chitin/Gel 01 or vaccinated with the protein vaccines alone. Positive responses in the comparative cervical skin test at 12 weeks after vaccination were only observed in animals vaccinated with s.c. BCG, 10(8)CFU oral BCG or a combination of 2 × 10(7)CFU oral BCG and CFP/Chitin/Gel 01. In conclusion, co-administration of a protein vaccine, administered by either systemic or mucosal routes with oral

Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short- and long-term pharmacokinetics.

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Heuberger, Jules A A C; Guan, Zheng; Oyetayo, Olubukayo-Opeyemi; Klumpers, Linda; Morrison, Paul D; Beumer, Tim L; van Gerven, Joop M A; Cohen, Adam F; Freijer, Jan

2015-02-01

Δ(9)-Tetrahydrocannobinol (THC), the main psychoactive compound of Cannabis, is known to have a long terminal half-life. However, this characteristic is often ignored in pharmacokinetic (PK) studies of THC, which may affect the accuracy of predictions in different pharmacologic areas. For therapeutic use for example, it is important to accurately describe the terminal phase of THC to describe accumulation of the drug. In early clinical research, the THC challenge test can be optimized through more accurate predictions of the dosing sequence and the wash-out between occasions in a crossover setting, which is mainly determined by the terminal half-life of the compound. The purpose of this study is to better quantify the long-term pharmacokinetics of THC. A population-based PK model for THC was developed describing the profile up to 48 h after an oral, intravenous, and pulmonary dose of THC in humans. In contrast to earlier models, the current model integrates all three major administration routes and covers the long terminal phase of THC. Results show that THC has a fast initial and intermediate half-life, while the apparent terminal half-life is long (21.5 h), with a clearance of 38.8 L/h. Because the current model characterizes the long-term pharmacokinetics, it can be used to assess the accumulation of THC in a multiple-dose setting and to forecast concentration profiles of the drug under many different dosing regimens or administration routes. Additionally, this model could provide helpful insights into the THC challenge test used for the development of (novel) compounds targeting the cannabinoid system for different therapeutic applications and could improve decision making in future clinical trials.

Pharmacokinetic Comparison of Once-Daily Topical Minocycline Foam 4% vs Oral Minocycline for Moderate-to-Severe Acne.

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Jones, Terry M; Ellman, Herman; deVries, Tina

2017-10-01

To characterize minocycline pharmacokinetics and relative bioavailability following multiple-dose topical administration of minocycline hydrochloride (HCl) foam 4% (FMX101 4%) as compared with single-dose oral administration of minocycline HCl extended-release tablets (Solodyn®) in subjects with moderate-to-severe acne. A Phase 1, single-center, nonrandomized, open-label, active-controlled, 2-period, 2-treatment crossover clinical study. The study included 30 healthy adults (mean age, 22.6 years; 90% white, and 60% females) who had moderate-to-severe acne. Subjects were assigned to first receive a single oral dose of a minocycline HCl extended-release tablet (approximately 1 mg/kg). At 10 days after the oral minocycline dose, topical minocycline foam 4% was applied, once daily for 21 days. Serial blood samples were obtained before and after administration of oral minocycline and each topical application of minocycline foam 4% on days 1, 12, and 21. Following oral administration of minocycline (approximately 1 mg/kg), plasma minocycline concentration increased until 3 hours, followed by a log-linear decrease over the remainder of the 96-hour sampling period. Following topical application of a 4-g maximal-use dose of minocycline foam 4% for 21 days, plasma minocycline concentration was very low, with geometric mean Cmax values ranging from 1.1 ng/mL to 1.5 ng/mL. Steady state was achieved by day 6. Overall, minocycline exposure with topical minocycline foam 4% was 730 to 765 times lower than that with oral minocycline. There was no evidence of minocycline accumulation over the 21 days of topical application of minocycline foam 4%. Topical minocycline foam 4% appeared to be safe and well tolerated, with no serious treatment-emergent adverse events (TEAEs), treatment-related TEAEs, or TEAEs that led to treatment discontinuation. Once-daily topical application of minocycline foam 4% did not lead to significant systemic exposure to minocycline. It appears to be a well

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

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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.

Low energy helium-neon laser prevents oral mucositis after high-dose chemo-radiotherapy: results of a double-blind randomized trial

International Nuclear Information System (INIS)

Cowen, Didier; Tardieu, Corinne; Resbeut, Michel; Hannoun-Levi, Jean-Michel; Alzieu, Claude; Schubert, Marc; Franquin, Jean-Claude

1996-01-01

correlation between successive scores of OM (r = 0.97, p < 0.001). Laser applications reduced maximum intensity of OM: mean CSOM was 132.3 in L+ pts vs 225.7 in L- pts (p=0.04). The improvement of DMI in L+ pts was statistically significant (p < 0.05) from d+2 to d+7. Mean number of days with grade III OM was 0.69 in L+ pts vs 2.41 in L- pts (p = 0.01). Laser applications reduced pain: mean cumulative daily scores of pain were 12.7 in L+ pts vs 20.3 in L- pts (p=0.05). Mean morphine administration over 21 days was 8.7 cg for L+ pts vs 14.7 cg for L- pts (p = 0.05). Saliva production and ability to swallow were improved among the L+ group (p 0.005, and p = 0.01 respectively). Requirement for parenteral nutrition was not improved (p = NS). Conclusion: Helium-Neon laser treatment was well tolerated, feasible in all cases, and reduced high dose chemoradiotherapy-induced oral mucositis. The use of He-Ne lasers should be evaluated in other patients experiencing oral mucositis such as those undergoing radiotherapy for head and neck cancers. Optimal schedule of treatment still needs to be defined

Oral Tranexamic Acid Reduces Transfusions in Total Knee Arthroplasty.

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Perreault, Roger E; Fournier, Christine A; Mattingly, David A; Junghans, Richard P; Talmo, Carl T

2017-10-01

Tranexamic acid (TXA) reduces intraoperative blood loss and transfusions in patients undergoing total knee arthroplasty. Although numerous studies demonstrate the efficacy of intravenous and topical TXA in these patients, few demonstrate the effectiveness and appropriate dosing recommendations of oral formulations. A retrospective cohort study was performed to evaluate differences in transfusion requirements in patients undergoing primary unilateral total knee arthroplasty with either no TXA (n = 866), a single-dose of oral TXA (n = 157), or both preoperative and postoperative oral TXA (n = 1049). Secondary outcomes included postoperative hemoglobin drop, total units transfused, length of stay, drain output, and cell salvage volume. Transfusion rates decreased from 15.4% in the no-oral tranexamic acid (OTA) group to 9.6% in the single-dose OTA group (P < .001) and 7% in the 2-dose group (P < .001), with no difference in transfusion rates between the single- and 2-dose groups (P = .390). In addition, postoperative hemoglobin drop was reduced from 4.2 g/dL in the no-OTA group to 3.5 g/dL in the single-dose group (P < .01) and to 3.4 g/dL in the 2-dose group (P < .01), without a difference between the single- and 2-dose groups (P = .233). OTA reduces transfusions, with greater ease of administration and improved cost-effectiveness relative to other forms of delivery. Copyright © 2017 Elsevier Inc. All rights reserved.

Improved anticoagulant effect of fucosylated chondroitin sulfate orally administered as gastro-resistant tablets.

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Fonseca, Roberto J C; Sucupira, Isabela D; Oliveira, Stephan Nicollas M C G; Santos, Gustavo R C; Mourão, Paulo A S

2017-04-03

Fucosylated chondroitin sulfate (FucCS) is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of unique branches of sulfated fucose. Although this glycosaminoglycan exerts an antithrombotic effect following oral administration, high doses are necessary to achieve the maximum effect. The diminished activity of FucCS following oral administration is likely due to its degradation in the gastrointestinal tract and its limited ability to cross the intestinal cell membranes. The latter aspect is particularly difficult to overcome. However, gastro-resistant tablet formulation may help limit the degradation of FucCS in the gastrointestinal tract. In the present work, we found that the oral administration of FucCS as gastro-resistant tablets produces a more potent and prolonged anticoagulant effect compared with its administration as an aqueous solution, with no significant changes in the bleeding tendency or arterial blood pressure. Experiments using animal models of arterial thrombosis initiated by endothelial injury demonstrated that FucCS delivered as gastro-protective tablets produced a potent antithrombotic effect, whereas its aqueous solution was ineffective. However, there was no significant difference between the effects of FucCS delivered as gastro-resistant tablets or as aqueous solution in a venous thrombosis model, likely due to the high dose of thromboplastin used. New oral anticoagulants tested in these experimental models for comparison showed significantly increased bleeding tendencies. Our study provides a framework for developing effective oral anticoagulants based on sulfated polysaccharides from marine organisms. The present results suggest that FucCS is a promising oral anticoagulant.

Oral ketamine for the treatment of pain and treatment-resistant depression†.

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Schoevers, Robert A; Chaves, Tharcila V; Balukova, Sonya M; Rot, Marije Aan Het; Kortekaas, Rudie

2016-02-01

Recent studies with intravenous (i.v.) application of ketamine show remarkable but short-term success in patients with MDD. Studies in patients with chronic pain have used different ketamine applications for longer time periods. This experience may be relevant for psychiatric indications. To review the literature about the dosing regimen, duration, effects and side-effects of oral, intravenous, intranasal and subcutaneous routes of administration of ketamine for treatment-resistant depression and pain. Searches in PubMed with the terms 'oral ketamine', 'depression', 'chronic pain', 'neuropathic pain', 'intravenous ketamine', 'intranasal ketamine' and 'subcutaneous ketamine' yielded 88 articles. We reviewed all papers for information about dosing regimen, number of individuals who received ketamine, number of ketamine days per study, results and side-effects, as well as study quality. Overall, the methodological strength of studies investigating the antidepressant effects of ketamine was considered low, regardless of the route of administration. The doses for depression were in the lower range compared with studies that investigated analgesic use. Studies on pain suggested that oral ketamine may be acceptable for treatment-resistant depression in terms of tolerability and side-effects. Oral ketamine, given for longer time periods in the described doses, appears to be well tolerated, but few studies have systematically examined the longer-term negative consequences. The short- and longer-term depression outcomes as well as side-effects need to be studied with rigorous randomised controlled trials. © The Royal College of Psychiatrists 2016.

Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study.

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Maha M Eissa

Full Text Available Miltefosine (MFS is an alkylphosphocholine used for the local treatment of cutaneous metastases of breast cancer and oral therapy of visceral leishmaniasis. Recently, the drug was reported in in vitro and preclinical studies to exert significant activity against different developmental stages of schistosomiasis mansoni, a widespread chronic neglected tropical disease (NTD. This justified MFS repurposing as a potential antischistosomal drug. However, five consecutive daily 20 mg/kg doses were needed for the treatment of schistosomiasis mansoni in mice. The present study aims at enhancing MFS efficacy to allow for a single 20mg/kg oral dose therapy using a nanotechnological approach based on lipid nanocapsules (LNCs as oral nanovectors. MFS was incorporated in LNCs both as membrane-active structural alkylphospholipid component and active antischistosomal agent. MFS-LNC formulations showed high entrapment efficiency (EE%, good colloidal properties, sustained release pattern and physical stability. Further, LNCs generally decreased MFS-induced erythrocyte hemolytic activity used as surrogate indicator of membrane activity. While MFS-free LNCs exerted no antischistosomal effect, statistically significant enhancement was observed with all MFS-LNC formulations. A maximum effect was achieved with MFS-LNCs incorporating CTAB as positive charge imparting agent or oleic acid as membrane permeabilizer. Reduction of worm load, ameliorated liver pathology and extensive damage of the worm tegument provided evidence for formulation-related efficacy enhancement. Non-compartmental analysis of pharmacokinetic data obtained in rats indicated independence of antischistosomal activity on systemic drug exposure, suggesting possible gut uptake of the stable LNCs and targeting of the fluke tegument which was verified by SEM. The study findings put forward MFS-LNCs as unique oral nanovectors combining the bioactivity of MFS and biopharmaceutical advantages of LNCs

Metabolism and disposition of N,N-dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca.

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Riba, Jordi; McIlhenny, Ethan H; Valle, Marta; Bouso, José Carlos; Barker, Steven A

2012-01-01

Ayahuasca is an Amazonian psychotropic plant tea obtained from Banisteriopsis caapi, which contains β-carboline alkaloids, chiefly harmine, harmaline and tetrahydroharmine. The tea usually incorporates the leaves of Psychotria viridis or Diplopterys cabrerana, which are rich in N,N-dimethyltryptamine (DMT), a psychedelic 5-HT(2A/1A/2C) agonist. The β-carbolines reversibly inhibit monoamine-oxidase (MAO), effectively preventing oxidative deamination of the orally labile DMT and allowing its absorption and access to the central nervous system. Despite increased use of the tea worldwide, the metabolism and excretion of DMT and the β-carbolines has not been studied systematically in humans following ingestion of ayahuasca. In the present work, we used an analytical method involving high performance liquid chromatography (HPLC)/electrospray ionization (ESI)/selected reaction monitoring (SRM)/tandem mass spectrometry(MS/MS) to characterize the metabolism and disposition of ayahuasca alkaloids in humans. Twenty-four-hour urine samples were obtained from 10 healthy male volunteers following administration of an oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight). Results showed that less than 1% of the administered DMT dose was excreted unchanged. Around 50% was recovered as indole-3-acetic acid but also as DMT-N-oxide (10%) and other MAO-independent compounds. Recovery of DMT plus metabolites reached 68%. Harmol, harmalol, and tetrahydroharmol conjugates were abundant in urine. However, recoveries of each harmala alkaloid plus its O-demethylated metabolite varied greatly between 9 and 65%. The present results show the existence in humans of alternative metabolic routes for DMT other than biotransformation by MAO. Also that O-demethylation plus conjugation is an important but probably not the only metabolic route for the harmala alkaloids in humans. Copyright © 2012 John Wiley & Sons, Ltd.

Oral administration of myostatin-specific recombinant Saccharomyces cerevisiae vaccine in rabbit.

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Liu, Zhongtian; Zhou, Gang; Ren, Chonghua; Xu, Kun; Yan, Qiang; Li, Xinyi; Zhang, Tingting; Zhang, Zhiying

2016-04-29

Yeast is considered as a simple and cost-effective host for protein expression, and our previous studies have proved that Saccharomyces cerevisiae can deliver recombinant protein and DNA into mouse dendritic cells and can further induce immune responses as novel vaccines. In order to know whether similar immune responses can be induced in rabbit by oral administration of such recombinant S. cerevisiae vaccine, we orally fed the rabbits with heat-inactivated myostatin-recombinant S. cerevisiae for 5 weeks, and then myostatin-specific antibody in serum was detected successfully by western blotting and ELISA assay. The rabbits treated with myostatin-recombinant S. cerevisiae vaccine grew faster and their muscles were much heavier than that of the control group. As a common experimental animal and a meat livestock with great economic value, rabbit was proved to be the second animal species that have been successfully orally immunized by recombinant S. cerevisiae vaccine after mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of single oral dose of tramadol on gastric secretions pH

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Khan Mueen Ullah

2015-01-01

Full Text Available Background: Tramadol is an atypical analgesic agent. It has been shown that intramuscular or intravenous injection tramadol is able to inhibit M3 muscarinic receptors. Tramadol is able to mediate smooth muscles contraction and glandular secretions. We have evaluated the effects of single oral dose of tramadol given preoperatively on gastric juices pH in patients electively scheduled for laparoscopic cholecystectomy. Materials and Methods: Sixty adult, American Society of Anesthesiologist I and II patients scheduled for laparoscopic cholecystectomy were included in the study. Patients were randomly assigned to receive either placebo (n = 30 or oral tramadol 50 mg (n = 30. General anesthesia was induced using propofol, fentanyl and cisatracurium. After induction of anesthesia 5 ml of gastric fluid was aspirated through orogastric tube. The gastric fluid pH was measured using pH meter. Result: There was no significant difference in the pH between the groups. Gastric pH of the placebo and tramadol groups was 1.97 versus 1.98 (P = 0.092 respectively. Conclusion: Preoperatively single oral dose of tramadol was unable to elevate the desired level of gastric acid secretions pH (>2.5. This may be due to pharmacokinetic disparity between the analgesic and pH elevating properties of tramadol.

Dose selection trial of metronomic oral vinorelbine monotherapy in patients with metastatic cancer: a hellenic cooperative oncology group clinical translational study

International Nuclear Information System (INIS)

Briasoulis, Evangelos; Vassias, Antonios; Klouvas, George; Boukovinas, Ioannis; Fountzilas, George; Syrigos, Kostantinos N; Kalofonos, Haralambos; Samantas, Epaminontas; Aravantinos, Gerasimos; Kouvatseas, George; Pappas, Periklis; Biziota, Eirini; Sainis, Ioannis; Makatsoris, Thomas; Varthalitis, Ioannis; Xanthakis, Ioannis

2013-01-01

Metronomic chemotherapy is considered an anti-angiogenic therapy that involves chronic administration of low-dose chemotherapy at regular short intervals. We investigated the optimal metronomic dose of oral vinorelbine when given as monotherapy in patients with metastatic cancer. Patients with recurrent metastatic breast (BC), prostate (PC) or non-small cell lung cancer (NSCLC) and adequate organ functions were randomly assigned to 30, 40 or 50 mg vinorelbine, taken orally three times a week. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or maximum 24 months. Primary endpoint was time-to-treatment failure (TTF) and secondary were progression-free survival (PFS), toxicity, changes in blood concentrations of angiogenesis-associated biomarkers and pharmacokinetics. Seventy-three patients were enrolled. Four-month TTF rate did not differ between the three arms: 25.9% (11.1%-46.2% 95% Confidence Interval), 33.3% (15.6%-55.3%) and 18.2% (5.2%-40.3%) for the 30 mg, 40 mg and 50 mg arms (p-value = 0.56). Objective response was seen in 2 patients with NSCLC (treated at 30 and 50 mg respectively), one with BC (at 40 m g) and one with PC (at 50 mg) and lasted from 4 to 100 weeks, with maximum response duration achieved at 50 mg. Adverse events were mild and negligible and did not differ between the three arms. Blood levels of vinorelbine reached steady state from the second week of treatment and mean values for the 30, 40 and 50 mg were respectively 1.8 ng/ml (SD 1.10), 2.2 ng/ml (SD 1.87) and 2.6 ng/ml (SD 0.69). Low pre-treatment blood concentrations of FGF2 and IL8 predicted favorable response to therapy (p values 0.02 and 0.006, respectively), while high levels of TEK gene transcript predicted treatment resistance. Considering the antitumor activity and response duration, the negligible toxicity of the highest dose investigated and the lack of drug accumulation over time, we suggest that 50 mg given three times a week is the

R-Limonene metabolism in humans and metabolite kinetics after oral administration.

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Schmidt, Lukas; Göen, Thomas

2017-03-01

We studied the R-limonene (LMN) metabolism and elimination kinetics in a human in vivo study. Four volunteers were orally exposed to a single LMN dose of 100-130 µg kg -1 bw. In each case, one pre-exposure and subsequently all 24 h post-exposure urine samples were collected. From two subjects, blood samples were drawn up to 5 h after exposure. The parent compound was analysed in blood using headspace GC-MS. The metabolites cis- and trans-carveol (cCAR), perillyl alcohol (POH), perillic acid (PA), limonene-1,2-diol (LMN-1,2-OH), and limonene-8,9-diol (LMN-8,9-OH) were quantified in both blood and urine using GC-PCI-MS/MS. Moreover, GC-PCI-MS full-scan experiments were applied for identification of unknown metabolites in urine. In both matrices, metabolites reached maximum concentrations 1-2 h post-exposure followed by rapid elimination with half-lives of 0.7-2.5 h. In relation to the other metabolites, LMN-1,2-OH was eliminated slowest. Nonetheless, overall renal metabolite elimination was completed within the 24-h observation period. The metabolite amounts excreted via urine corresponded to 0.2 % (cCAR), 0.2 % (tCAR), <0.1 % (POH), 2.0 % (PA), 4.3 % (LMN-1,2-OH), and 32 % (LMN-8,9-OH) of the orally administered dose. GC-PCI-MS full-scan analyses revealed dihydroperillic acid (DHPA) as an additional LMN metabolite. DHPA was estimated to account for 5 % of the orally administered dose. The study revealed that human LMN metabolism proceeds fast and is characterised by oxidation mainly of the exo-cyclic double bond but also of the endo-cyclic double bond and of the methyl side chain. The study results may support the prediction of the metabolism of other terpenes or comparable chemical structures.

Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

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Putcha, Lakshmi; Crady, Camille; Putcha, Lakshmi

2012-01-01

Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

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

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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.

Corticosteroid administration in oral and orthognathic surgery: a systematic review of the literature and meta-analysis

DEFF Research Database (Denmark)

Dan, Anne E B; Thygesen, Torben H; Pinholt, Else M

2010-01-01

was made. The primary predictor variable was CS administration and the outcome variables were edema, pain, and infection. A meta-analysis was performed. The risk of other side effects was evaluated through a simple review. RESULTS: In oral surgery, most clinical trials showed a significant decrease...... toward a neuroregeneration effect, but no statistical analysis could be performed. Regarding the risk of other side effects, in oral surgery, a minimal risk of chronic adrenal suppression was seen; in orthognathic surgery, an elevated risk of avascular osteonecrosis, steroid-induced psychosis......, and adrenal suppression was seen. There were no reports of decreased healing. CONCLUSION: These findings suggest that the administration of CS in oral surgery decreases edema and pain significantly, with no higher risk of infection and with a minimum risk of other side effects....

Sumatriptan (oral route of administration) for acute migraine attacks in adults

Science.gov (United States)

Derry, Christopher J; Derry, Sheena; Moore, R Andrew

2014-01-01

Background Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Objectives To determine the efficacy and tolerability of oral sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011. Selection criteria We included randomised, double-blind, placebo- and/or active-controlled studies using oral sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm. Data collection and analysis Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or ‘risk ratio’) and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment. Main results Sixty-one studies (37,250 participants) compared oral sumatriptan with placebo or an active comparator. Most of the data were for the 50 mg and 100 mg doses. Sumatriptan surpassed placebo for all efficacy outcomes. For sumatriptan 50 mg versus placebo the NNTs were 6.1, 7.5, and 4.0 for pain-free at two hours and headache relief at one and two hours, respectively. NNTs for sustained pain-free and sustained headache relief during the 24 hours postdose were 9.5 and 6.0, respectively. For sumatriptan 100 mg versus placebo the NNTs were 4.7, 6.8, 3.5, 6.5, and 5.2, respectively, for the same outcomes. Results for the 25 mg dose were similar to the 50 mg dose, while sumatriptan 100 mg was significantly better than 50 mg for pain-free and headache relief at two hours, and for sustained pain-free during 24 hours. Treating early, during

Oral sodium phosphate solution: a review of its use as a colorectal cleanser.

Science.gov (United States)

Curran, Monique P; Plosker, Greg L

2004-01-01

Oral sodium phosphate solution (Fleet Phospho-soda, Casen-Fleet Fosfosoda is a low-volume, hyperosmotic agent used as part of a colorectal-cleansing preparation for surgery, x-ray or endoscopic examination. The efficacy and tolerability of oral sodium phosphate solution was generally similar to, or significantly better than, that of polyethylene glycol (PEG) or other colorectal cleansing regimens in patients preparing for colonoscopy, colorectal surgery or other colorectal-related procedures. Generally, oral sodium phosphate solution was significantly more acceptable to patients than PEG or other regimens. The use of this solution should be considered in most patients (with the exception of those with contraindications) requiring colorectal cleansing. PHARMACOLOGICAL PROPERTIES: After the first and second 45 mL dose of oral sodium phosphate solution, the mean time to onset of bowel activity was 1.7 and 0.7 hours and the mean duration of activity was 4.6 and 2.9 hours. Bowel activity ceased within 4 hours of administration of the second dose in 83% of patients. Elevations in serum phosphorus and falls in serum total and ionised calcium from baseline occurred during the 24 hours after administration of oral sodium phosphate solution in seven healthy volunteers. These changes were not associated with significant changes in clinical assessments. The decrease in serum potassium levels after administration of oral sodium phosphate solution was negatively correlated with baseline intracellular potassium levels. A regimen that administered the first dose of sodium phosphate on the previous evening and a second dose on the morning of the procedure (10-12 hours apart) was significantly more effective than PEG-based regimens for colorectal cleansing in preparation for colonoscopy, sigmoidoscopy or colorectal surgery. A regimen that administered both doses of oral sodium phosphate on the day prior to the procedure offered no colorectal cleansing advantage over PEG

Protection from radiation injury through oral administration of PF4 gene carried by attenuated salmonella

International Nuclear Information System (INIS)

Zhao Lihua; Liu Bin; Yu Xiaofei; Zhang Lei; Han Zhongchao

2005-01-01

Objective: To investigate the in vivo radiation protection effect of PF4 by oral administration of attenuated salmonella as the carrier in mice. Methods: The eukaryotic vector pIRES2-EGFP-carried PF4 gene was transferred into an aroA-autotrophic mutant of salmonella typhimurium (SL3261), which was administered orally to BALBPc mice at 1x10 8 PFu once every interval three days. At 12 hours after the third oral administration the mice were subjected to a total body irradiation (TBI) of 700 cGy by a 60 Co source. The protective effect of SL3261/PF4 was determined by detection GFP ( green fluorescence protein) expression in tissues, peripheral blood count, culture of bone marrow colony-forming cells and survival time of mice. Results: Expression of GFP could be detected in the liver, spleen, intestine, kidney, peripheral blood and bone marrow. On days 7 and 14 after irradiation, Compared to controls, there were obvious differences in number of bone marrow mononuclear cells, CFU-GM (granulocyte-macrophage colony-forming unit ) and HPP-CFC (high proliferating potential-colony-forming cells) of mice treated with SL3261/PF4 (P<0.05) as well as prolongation of the survival time. Conclusion: These data demonstrate for the first time that PF4 protects mice from TBI injury and accelerates recovery of hematopoiesis by oral administration of attenuated salmonella carrying PF4 gene. (authors)

Oral and nasal administration of chicken type II collagen suppresses adjuvant arthritis in rats with intestinal lesions induced by meloxicam.

Science.gov (United States)

Zheng, Yong-Qiu; Wei, Wei; Shen, Yu-Xian; Dai, Min; Liu, Li-Hua

2004-11-01

To investigate the curative effects of oral and nasal administration of chicken type II collagen (CII) on adjuvant arthritis (AA) in rats with meloxicam-induced intestinal lesions. AA model in Sprague-Dawley (SD) rats with or without intestinal lesions induced by meloxicam was established and those rats were divided randomly into six groups which included AA model, AA model+meloxicam, AA model+oral CII, AA model+nasal CII, AA model+ meloxicam+oral C II and AA model+meloxicam+nasal CII (n = 12). Rats was treated with meloxicam intragastrically for 7 d from d 14 after immunization with complete Freund's adjuvant (CFA), and then treated with chicken CII intragastrically or nasally for 7 d. Histological changes of right hind knees were examined. Hind paw secondary swelling and intestinal lesions were evaluated. Synoviocyte proliferation was measured by 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) method. Activities of myeloperoxidase (MPO) and diamine oxidase (DAO) from supernatants of intestinal homogenates were assayed by spectrophotometric analysis. Intragastrical administration of meloxicam (1.5 mg/kg) induced multiple intestinal lesions in AA rats. There was a significant decrease of intestinal DAO activities in AA+meloxicam group (P<0.01) and AA model group (P<0.01) compared with normal group. DAO activities of intestinal homogenates in AA+meloxicam group were significantly less than those in AA rats (P<0.01). There was a significant increase of intestinal MPO activities in AA+meloxicam group compared with normal control (P<0.01). Oral or nasal administration of CII (20 microg/kg) could suppress the secondary hind paw swelling(P<0.05 for oral CII; P<0.01 for nasal CII), synoviocyte proliferation (P<0.01) and histopathological degradation in AA rats, but they had no significant effects on DAO and MPO changes. However, oral administration of CII (20 microg/kg) showed the limited efficacy on arthritis in AA+meloxicam model and the

Disposition and metabolism of glyphosate in the Sprague Dawley rat following oral administration

International Nuclear Information System (INIS)

Brewster, D.W.; Warren, J.A.; Hopkins, W.E.

1991-01-01

Five groups of male SD rats were administered 14 C-labelled glyphosate, (N-[(phosphonomethyl)glycine]) by gavage at a dose level of 10 mg/kg. Animals were killed 2, 6.3, 28, 96 and 168 hours after dosing and the amount of glyphosate-derived material in various organs and excreta were determined. In addition, the metabolic profile in tissues containing > 1% of the administered dose was evaluated. Approximately 93% of the body burden 2 hours after administration was associated with the GI contents and small intestinal tissue. The total body burden 7 days after administration was ∼1% of the dose. Only the kidneys, small intestine, colon, bone, GI contents, residual carcass contained > 1% of the dose 6 hours after administration and the metabolic profiles of these tissues indicated that ∼100% of the body burden was present as unmetabolized parent material. Glyphosate was rapidly eliminated from these tissues with halflives ranging from 20 to 90 hours. A minor metabolite comprising < 0.1% of the dose was detected in the GI contents and colon tissue of 3 animals. Less than 40% of the administered dose was absorbed from the gut and glyphosate was rapidly eliminated from the body with urine and feces being equally important routes of elimination. The whole body halflife was approximately 52 hours. The results from this study indicate that no toxic metabolites of glyphosate were produced, as there was little evidence of metabolism, and essentially 100% of the body burden was parent glyphosate with no significant persistence of accumulated material

Effects of prolonged oral administration of fumonisin B1 and aflatoxin B1 in rats.

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Pozzi, C R; Corrêa, B; Xavier, J G; Direito, G M; Orsi, R B; Matarazzo, S V

2001-01-01

The effects of prolonged oral administration (21 days) of fumonisin B1 (FB1) and aflatoxin B1 (AFB1) were evaluated on male Wistar rats. The animals were housed in individual metabolic cages and submitted to the following treatments: 1-0 microg AFB1 + 0 mg FB1/100g bw.; 2-72 microg AFB1+ 0 mg FB1/100 g bw; 3-0 microg AFB1 + 0.5 mg FB1 g bw; 4-0 microg AFB1 + 1.5 mg FB1/100 g bw; 5-72 microg AFB1 + 0.5 mg FB1/100g bw; 6-72 microgAFB1 + 1.5 mg FB1/100g bw. On day 21, the rats were sacrificed for evaluation. The results showed that treated animals presented differences in body weight and absolute/relative weights of liver and kidney as well as altered hepatic function and cholesterol blood levels. Rats fed with the greatest doses of AFB1 and FB1 gained less weight (2.79 g/day) at the end of the experimental period; their blood concentrations of liver enzymes aspartate aminotransferase (AST) and alkaline phosphatase (AP) were above control levels (130.35 micro/l and 471.00 micro/l, respectively). Blood cholesterol increased in the groups treated with the highest dose of FB1 or FB1 associated with AFB1. Histopathology revealed the occurrence of apoptosis in the liver of rats exposed to FB1. The association of aflatoxin B1 with fumonisin B1 at higher dose probably potentiated the effects of the higher dose of fumonisin B1 acting singly.

The anti emetic effect of oral administration of ondansetron or granisetron in macacus cynomolgus exposed to mixed neutron-gamma irradiation

International Nuclear Information System (INIS)

Martin, C.; Roman, V.; Martin, S.; Janodet, D.; Fatome, M.

1995-01-01

Nausea and vomiting are the most often observed symptoms in the course of the early radiation syndrome. Their prevention has long been difficult because of the low effectiveness and side-effects of most antiemetics. There is a clear evidence that 5HT 3 receptor antagonists such as ondansetron and granisetron are highly effective to prevent radiation-induced emesis without any side-effect. We studied the prophylactic effectiveness of their oral administration to macacus cynomolgus, for mixed neutron-gamma whole-body exposure, tat high dose rates. Doses of 4 mg of ondansetron or 1 mg of granisetron were administered before, or after, or both before and after irradiation. The treatment was effective when administered both before and after radiation exposure. It was significant but incomplete if administered once. Post-irradiation administration is interesting, particularly in case of accident. Both antiemetic drugs were well tolerated. Their effectiveness and tolerance are apparently comparable. The 5HT 3 receptor antagonists represent a much improved treatment for radiation-induced nausea and vomiting by completely inhibiting emesis, if administered before and after irradiation. Unwanted sedation and extra-pyramidal side-effects, usually associated with the clinical use of D 2 receptor antagonists, were not observed. (authors). 40 refs., 5 tabs

Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts.

Science.gov (United States)

Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

2013-09-01

This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.

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)

Safety of 8-weeks oral administration of Arctium lappa L.

Science.gov (United States)

Bok, So-Hyeon; Cho, Seung Sik; Bae, Chun-Sik; Park, Dae-Hun; Park, Kyung-Mok

2017-09-01

Recently, worldwide dietary reference intakes have been considered an important guideline for public health. Some governments and the World Health Organization (WHO) provide guidelines concerning dietary intake. Although an ingredient may have a history of use as a culinary material, changes in the environment over time suggest that the acceptable maximum intake each of food/culinary material should be regularly evaluated. Arctium lappa L. has been used as a culinary material for many centuries in Korea and Japan and some recent studies have reported related therapeutic effects. However, there are no reports on the safety of repeated oral administration. In this study, we evaluated the safety of a 8-weeks repeated oral intake of A. lappa . We concluded that treatment with lappa , which was within the safety range, resulted in body weight decrease and blood glucose suppression.

Distribution of 14C after oral administration of [U-14C]labeled methyl linoleate hydroperoxides and their secondary oxidation products in rats

International Nuclear Information System (INIS)

Oarada, M.; Miyazawa, T.; Kaneda, T.

1986-01-01

To study the toxicity of low molecular weight (LMW) compounds formed during the autoxidation of oils, 14 C-labeled primary monomeric compounds (methyl linoleate hydroperoxides) and secondary oxidation products, i.e., polymer and LMW compounds prepared from autoxidized methyl [U- 14 C]linoleate hydroperoxides (MLHPO) were orally administered to rats, and their radioactive distributions in tissues and organs were compared. The polymeric fraction consisted mainly of dimers of MLHPO. For the LMW fraction, 4-hydroxy-2-nonenal, 8-hydroxy methyl octanoate and 10-formyl methyl-9-decenoate were identified as major constituents by gas chromatography-mass spectrometry (GC-MS) after chemical reduction and derivatization. When LMW compounds were administered to rats, 14 CO 2 expiration and the excreted radioactivity in urine in 12 hr were significantly higher than those from polymer or MLHPO administration. Maximum 14 CO 2 expiration appeared 2-4 hr after the dose of LMW compounds. Radioactivity of the upper part of small intestines six hr after the dose of LMW compounds was higher than the values from administered polymer or MLHPO. The remaining radioactivity in the digestive contents and feces 12 hr after administration of LMW compounds was much lower than the values observed from administered polymer or MLHPO. Among internal organs, the liver contained the highest concentration of radioactivities from polymer, MLHPO and LMW fractions, and an especially higher level of radioactivity was found in liver six hr after the administration of LMW compounds. Six hours after the dose of LMW compounds, a relatively higher level of radioactivity also was detected in kidney, brain, heart and lung

Prospective Evaluation to Establish a Dose Response for Clinical Oral Mucositis in Patients Undergoing Head-and-Neck Conformal Radiotherapy

International Nuclear Information System (INIS)

Narayan, Samir; Lehmann, Joerg; Coleman, Matthew A.; Vaughan, Andrew; Yang, Claus Chunli; Enepekides, Danny; Farwell, Gregory; Purdy, James A.; Laredo, Grace; Nolan, Kerry A.S.; Pearson, Francesca S.; Vijayakumar, Srinivasan

2008-01-01

Purpose: We conducted a clinical study to correlate oral cavity dose with clinical mucositis, perform in vivo dosimetry, and determine the feasibility of obtaining buccal mucosal cell samples in patients undergoing head-and-neck radiation therapy. The main objective is to establish a quantitative dose response for clinical oral mucositis. Methods and Materials: Twelve patients undergoing radiation therapy for head-and-neck cancer were prospectively studied. Four points were chosen in separate quadrants of the oral cavity. Calculated dose distributions were generated by using AcQPlan and Eclipse treatment planning systems. MOSFET dosimeters were used to measure dose at each sampled point. Each patient underwent buccal sampling for future RNA analysis before and after the first radiation treatment at the four selected points. Clinical and functional mucositis were assessed weekly according to National Cancer Institute Common Toxicity Criteria, Version 3. Results: Maximum and average doses for sampled sites ranged from 7.4-62.3 and 3.0-54.3 Gy, respectively. A cumulative point dose of 39.1 Gy resulted in mucositis for 3 weeks or longer. Mild severity (Grade ≤ 1) and short duration (≤1 week) of mucositis were found at cumulative point doses less than 32 Gy. Polymerase chain reaction consistently was able to detect basal levels of two known radiation responsive genes. Conclusions: In our sample, cumulative doses to the oral cavity of less than 32 Gy were associated with minimal acute mucositis. A dose greater than 39 Gy was associated with longer duration of mucositis. Our technique for sampling buccal mucosa yielded sufficient cells for RNA analysis using polymerase chain reaction

Toxicity of strontium-90 depending on the way of its administration to animal organisms

International Nuclear Information System (INIS)

Shvedov, V.L.

1978-01-01

Toxicity of strontium-90 administered orally is almost thrice lower than that after parenteral administration. The values of the doses absorbed in the critical organ of rats, corresponding to LDsub(50/30), were 2400 to 2600 rad irrespective of the route of the radionuclide administration

Evaluation of renal function following administration of ethane-1-hydroxy-1,1-biphosphonate (EHBP) in animals submitted to oral intoxication with uranyl nitrate

International Nuclear Information System (INIS)

Martinez, A.B.; Mandalunis, P.M.; Bozal, C.B.; Cabrini, Romulo L.; Ubios, A.M.

2003-01-01

Workers involved in the processes of extraction, purification and manufacture of uranium of nuclear plants are occupationally exposed to both natural and enriched uranium. Several chelating agents (TIRON, EDTA, BAI, etc.) have been tested in terms of their capacity to sequester uranium before it reaches its target organs. Our laboratory has studied a first generation biphosphonate, ethane-1-hydroxy-1,1-biphosphonate (EHBP). We have shown that treatment with EHBP induces survival rates of 75% and 100% in adult and suckling rats respectively intoxicated with an intraperitoneal injection of uranyl nitrate. There are no data available to date on the renal function following treatment with EBHP to counteract the toxic effects of an oral lethal dose of uranyl nitrate. The aim of the present study was to assay creatininemia and uremia as end-points to assess renal function. The results obtained reveal that the alterations in renal function induced by oral uranyl nitrate intoxication can be reduced at 48 hours and reverted at 14 days by subcutaneous or oral administration of EHBP. (author)

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

Science.gov (United States)

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.

Persistence of the oral probiotic Streptococcus salivarius M18 is dose dependent and megaplasmid transfer can augment their bacteriocin production and adhesion characteristics.

Science.gov (United States)

Burton, Jeremy P; Wescombe, Philip A; Macklaim, Jean M; Chai, Melissa H C; Macdonald, Kyle; Hale, John D F; Tagg, John; Reid, Gregor; Gloor, Gregory B; Cadieux, Peter A

2013-01-01

Bacteriocin-producing probiotic Streptococcus salivarius M18 offers beneficial modulatory capabilities within the oral microbiome, apparently through potent inhibitory activity against potentially deleterious bacteria, such as Streptococcus pyogenes. The oral cavity persistence of S. salivarius M18 was investigated in 75 subjects receiving four different doses for 28 days. Sixty per cent of the subjects already had some inhibitor-producing S. salivarius in their saliva prior to probiotic intervention. Strain M18's persistence was dependent upon the dose, but not the period of administration. Culture analysis indicated that in some individuals the introduced strain had almost entirely replaced the indigenous S. salivarius, though the total numbers of the species did not increase. Selected subjects showing either high or low probiotic persistence had their salivary populations profiled using Illumina sequencing of the V6 region of the 16S rRNA gene. Analysis indicated that while certain bacterial phenotypes were markedly modulated, the overall composition of the oral microbiome was not modified by the probiotic treatment. Megaplasmids encoding bacteriocins and adhesion factors were transferred in vitro to generate a transconjugant S. salivarius exhibiting enhanced antimicrobial production and binding capabilities to HEp-2 cells. Since no widespread perturbation of the existing indigenous microbiota was associated with oral instillation and given its antimicrobial activity against potentially pathogenic streptococci, it appears that application of probiotic strain M18 offers potential low impact alternative to classical antibiotic prophylaxis. For candidate probiotic strains having relatively poor antimicrobial or adhesive properties, unique derivatives displaying improved probiotic performance may be engineered in vitro by megaplasmid transfer.

Persistence of the oral probiotic Streptococcus salivarius M18 is dose dependent and megaplasmid transfer can augment their bacteriocin production and adhesion characteristics.

Directory of Open Access Journals (Sweden)

Jeremy P Burton

Full Text Available Bacteriocin-producing probiotic Streptococcus salivarius M18 offers beneficial modulatory capabilities within the oral microbiome, apparently through potent inhibitory activity against potentially deleterious bacteria, such as Streptococcus pyogenes. The oral cavity persistence of S. salivarius M18 was investigated in 75 subjects receiving four different doses for 28 days. Sixty per cent of the subjects already had some inhibitor-producing S. salivarius in their saliva prior to probiotic intervention. Strain M18's persistence was dependent upon the dose, but not the period of administration. Culture analysis indicated that in some individuals the introduced strain had almost entirely replaced the indigenous S. salivarius, though the total numbers of the species did not increase. Selected subjects showing either high or low probiotic persistence had their salivary populations profiled using Illumina sequencing of the V6 region of the 16S rRNA gene. Analysis indicated that while certain bacterial phenotypes were markedly modulated, the overall composition of the oral microbiome was not modified by the probiotic treatment. Megaplasmids encoding bacteriocins and adhesion factors were transferred in vitro to generate a transconjugant S. salivarius exhibiting enhanced antimicrobial production and binding capabilities to HEp-2 cells. Since no widespread perturbation of the existing indigenous microbiota was associated with oral instillation and given its antimicrobial activity against potentially pathogenic streptococci, it appears that application of probiotic strain M18 offers potential low impact alternative to classical antibiotic prophylaxis. For candidate probiotic strains having relatively poor antimicrobial or adhesive properties, unique derivatives displaying improved probiotic performance may be engineered in vitro by megaplasmid transfer.

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

High-dose-rate brachytherapy using molds for oral cavity cancer. The technique and its limitations

International Nuclear Information System (INIS)

Nishimura, Yasumasa; Yokoe, Yoshihiko; Nagata, Yasushi; Okajima, Kaoru; Nishida, Mitsuo; Hiraoka, Masahiro

1998-01-01

With the availability of a high-dose-rate (HDR) remote afterloading device, a Phase I/II protocol was initiated at our institution to assess the toxicity and efficacy of HDR intracavitary brachytherapy, using molds, in the treatment of squamous cell carcinomas of the oral cavity. Eight patients with squamous cell carcinoma of the oral cavity were treated by the technique. The primary sites of the tumors were the buccal mucosa, oral floor, and gingiva. Two of the buccal mucosal cancers were located in the retromolar trigon. For each patient, a customized mold was fabricated, in which two to four afterloading catheters were placed for an 192 Ir HDR source. Four to seven fractions of 3-4 Gy, 5 mm below the mold surface, were given following external radiation therapy of 40-60 Gy/ 2 Gy. The total dose of HDR brachytherapy ranged from 16 to 28Gy. Although a good initial complete response rate of 7/8 (88%) was achieved, there was local recurrence in four of these seven patients. Both of the retromolar trigon tumors showed marginal recurrence. No serious (e.g., ulcer or bone exposure) late radiation damage has been observed thus far in the follow up period of 15-57 months. High-dose-rate brachytherapy using the mold technique seems a safe and useful method for selected early and superficial oral cavity cancer. However, it is not indicated for thick tumors and/or tumors located in the retromolar trigon. (author)

Oral administration of a medium containing both D-aspartate-producing live bacteria and D-aspartate reduces rectal temperature in chicks.

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Do, P H; Tran, P V; Bahry, M A; Yang, H; Han, G; Tsuchiya, A; Asami, Y; Furuse, M; Chowdhury, V S

2017-10-01

1. The aim of this study was to investigate the effects on the rectal temperature of young chicks of the oral administration of a medium that contained both live bacteria that produce D-aspartate (D-Asp) and D-Asp. 2. In Experiment 1, chicks were subjected to chronic oral administration of either the medium (containing live bacteria and 2.46 μmol D-Asp) or water from 7 to 14 d of age. Plasma-free amino acids as well as mitochondrial biogenic gene expression in the breast muscle were analysed. In Experiment 2, 7-d-old chicks were subjected to acute oral administration of the above medium or of an equimolar amount of D-Asp to examine their effect on changes in rectal temperature. In Experiment 3, after 1 week of chronic oral administration of the medium, 14-d-old chicks were exposed to either high ambient temperature (HT; 40 ± 1°C, 3 h) or control thermoneutral temperature (CT; 30 ± 1°C, 3 h) to monitor the changes in rectal temperature. 3. Chronic, but not acute, oral administration of the medium significantly reduced rectal temperature in chicks, and a chronic effect also appeared under HT conditions. 4. Chronic oral administration of the medium significantly reduced the mRNA abundance of the avian uncoupling protein (avUCP) in the breast muscle, but led to a significant increase in avian adenine nucleotide translocator (avANT) mRNA in the same muscle. 5. (a) These results indicate that the medium can reduce body temperature through the decline in avUCP mRNA expression in the breast muscle that may be involved in reduced mitochondrial proton leaks and heat production. (b) The increase in avANT further suggests a possible enhancement of adenosine triphosphate (ATP) synthesis.

Effects of a prolonged administration of valepotriates in rats on the mothers and their offspring.

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Tufik, S; Fujita, K; Seabra, M de L; Lobo, L L

1994-01-01

Valeriana officinalis L. (Valerianaceae) is widely known to be associated with sedative properties. The effects of a valepotriates mixtures on mothers and progeny were evaluated in rats. A 30-day administration of valepotriates did not change the average length of estral cycle, nor the number of estrous phases during this period. Also, there were no changes on the fertility index. Fetotoxicity and external examination studies did not show differences, although internal examination revealed an increase in number of retarded ossification after the highest doses employed--12 and 24 mg/kg. No changes were detected in the development of the offspring after treatment during pregnancy. As for temperature, valepotriates caused a hypothermizant effect after administration by the intraperitoneal route but not after oral administration. Generally, the valepotriates employed induced some alterations after administration by the intraperitoneal route, but doses given orally were innocuous to pregnant rats and their offspring.

A 4-Week Repeated-Dose Oral Toxicity Study of Bojungikgi-Tang in Crl:CD Sprague Dawley Rats

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Sae-Rom Yoo

2017-01-01

Full Text Available Traditional herbal medicines have been used for centuries in Asian countries. However, recent studies have led to increasing concerns about the safety and toxicity of herbal prescriptions. Bojungikgi-tang (BJIGT, a herbal decoction, has been used in Korea to improve physical strength. To establish the safety information, BJIGT water extract was evaluated in a 4-week repeated-dose oral toxicity test in Crl:CD Sprague Dawley rats. BJIGT was orally administered in daily doses of 0, 500, 1000, and 2000 mg/kg/day for 4 weeks via oral gavage in male and female rats. We examined the mortality, clinical signs, body weight change, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters. No significant changes were observed in mortality, clinical sings, body weight, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters between the control group and the BJIGT-treated groups in the rats of both sexes. The results indicate that BJIGT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. Thus, this concentration is considered the nonobservable effect dose in rats and is appropriate for a 13-week subchronic toxicity study.

Minimization of CYP2D6 Polymorphic Differences and Improved Bioavailability via Transdermal Administration: Latrepirdine Example.

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Chew, Marci L; Mordenti, Joyce; Yeoh, Thean; Ranade, Gautam; Qiu, Ruolun; Fang, Juanzhi; Liang, Yali; Corrigan, Brian

2016-08-01

Transdermal delivery has the potential to offer improved bioavailability by circumventing first-pass gut and hepatic metabolism. This study evaluated the pharmacokinetics of oral immediate release and transdermal latrepirdine in extensive and poor CYP2D6 metabolizers (EM/PM). Latrepirdine transdermal solution was prepared extemporaneously. The solution was applied with occlusive dressing to upper or middle back for 24 h. Each subject received a single dose of 8.14 mg oral, 5 mg transdermal, and 10 mg transdermal (EMs only) latrepirdine free base in a fixed sequence. Twelve EMs and 7 PMs (50-79 years) enrolled and completed the study. Latrepirdine was well tolerated following both routes of administration. Dose-normalized latrepirdine total exposures were approximately 11-fold and 1.5-fold higher in EMs and PMs, respectively following administration of transdermal relative to oral. Differences between EM and PM latrepirdine exposures were decreased, with PMs having 1.9- and 2.7-fold higher peak and total exposures, respectively, following transdermal administration compared to 11- and 20-fold higher exposures, respectively, following oral administration. Transdermal delivery can potentially mitigate the large intersubject differences observed with compounds metabolized primarily by CYP2D6. Transdermal delivery was readily accomplished in the clinic using an extemporaneously prepared solution [NCT00990613].

[Pharmacokinetics of 8-O-acetylharpagide and harpagide after oral administration of Ajuga decumbens extract in beagle dog].

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Wen, Bin-Yu; Li, Jian-Rong

2013-06-01

8-O-acetylharpagide and harpagide are two kinds of effective component of Ajuga decumbens extract. A sensitive LC-MS/MS method has been established for pharmacokinetics of 8-O-acetylharpagide and harpagide in beagle dog after oral administration of from A. decumbens extract. Female beagle dogs received orally 12.9, 25.7 mg x kg(-1) p. o. Concentrations of 8-O-acetylharpagide and harpagide in plasma were determined by LC-MS/MS method at different time points and all pharmacokinetic parameters were estimated by non-compartment analysis. The mobile phase consisted of 0.1% formic acid in water (A) and acetonitrile (B), which was run at a flow rate of 0.3 mL x min(-1). Chromatographic separation was achieved on an Agilent ZORBAX XDB-C18 column (2.1 mm x 50 mm, 3.5 microm) using a gradient elution of 5% B at 0-2 min, 95% B at 2. 1-5 min and 5% B at 5. 1-10 min. All analytes, including the IS, were monitored under positive ionization conditions and quantified in MRM mode with transitions of m/z 429.2-369.2 for 8-O-acetylharpagide, m/z 387.2-207.2 for harpagide, and m/z 149.2-103.1 for IS. High purity nitrogen was employed as both the nebulizing and drying gas. Other parameters of the mass spectrometer were optimized as follows: drying gas flow 10.0 L x min(-1); drying gas temperature 300 degrees C; capillary voltage 4 000 V. Results showed that 8-O-acetylharpagide and harpagide showed a dose-dependence profile. T(max) of 8-O-acetylharpagide is 1.7 h, and T(max) of harpagide is 1.57 h, which was higher than T(max) of 8-O-acetylharpagide and harpagide after oral administration of from A. decumbens extract in rats. The different pharmacokinetic parameters may be due to the species differences of rat and beagle dog.

Evaluation of an oral transmucosal administration of dexmedetomidine-butorphanol and dexmedetomidine-methadone in dogs.

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Daniela Gioeni

2017-05-01

Full Text Available Oral transmucosal (OTM delivery is a simple and painless method for sedative administration in veterinary medicine and allows a rapid absorption without a first-pass metabolism by the liver (Porters et al. 2014.. OTM is particularly useful in aggressive animals (Santos et al. 2010. The aim of this study is to evaluate the efficacy of the OTM route in dogs for sedative administration in comparison with intramuscular (IM injection. 24 mix-bread dogs undergoing soft tissue surgery or diagnostic procedures were randomly divided in 4 groups (n = 6: two groups received OTM administration of dexmedetomidine (10 µg/kg-1 together with butorphanol (0.2 mg/kg-1, BTF-OTM group or methadone (0.2mg/kg-1, MTD-OTM group; two groups received intramuscular (IM administration of dexmedetomidine (5 µg/kg-1 together with butorphanol (0.2 m/kg-1, BTF-IM group or methadone (0.2 mg/kg-1, MTD-IM. Heart rate (HR, respiratory rate (RR, sedation score (Gruney et al. 2009 and side effects were recorded 10 (T10, 20 (T20 and 30 (T30 minutes after premedication. Induction was performed at T30 with titrate-to-effect propofol administration and the dosage required was recorded. At each time point BTF-IM group showed a statistically lower HR compared to BTF-OTM; RR was statistically lower at T10 in MTD-OTM group (21.33 ± 8.64 pm compared to BTF-OTM (46.16 ± 17.98; Dogs in group MTD-IM reached a higher sedation scores at each time point compared to MTD-OTM. The induction dose of propofol appears comparable among groups. Marked vasoconstriction was observed after OTM administration, as probably related to α2-agonists use. Emesis and sialorrhea occurred in two subjects of MTD-OTM group while only one dog presented sialorrhea in BTF-OTM group. In conclusion, OTM administration appears effective and easy to perform; it takes a longer time to achieve a good sedation score, probably related to a gradual absorption of drugs that also leads to a more gradual hemodynamic effects.

Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice

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Olakunle James Onaolapo

2013-01-01

Full Text Available This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.