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Pharmacokinetics of Intravenous and Oral Phenobarbital Sodium in Healthy Goats

Phenobarbital is a common drug used to manage epilepsy in goats. However, the recommended dose and dosing frequency are based on studies in dogs and horses. Studies describing the pharmacokinetics of phenobarbital when administered orally and assessing changes in behavior with concurrent electroence...

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Autores principales: Yates, Liana M., Aleman, Monica, Knych, Heather K., Knipe, Marguerite F., Crowe, Chelsea M., Chigerwe, Munashe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046625/
https://www.ncbi.nlm.nih.gov/pubmed/32154280
http://dx.doi.org/10.3389/fvets.2020.00086
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author Yates, Liana M.
Aleman, Monica
Knych, Heather K.
Knipe, Marguerite F.
Crowe, Chelsea M.
Chigerwe, Munashe
author_facet Yates, Liana M.
Aleman, Monica
Knych, Heather K.
Knipe, Marguerite F.
Crowe, Chelsea M.
Chigerwe, Munashe
author_sort Yates, Liana M.
collection PubMed
description Phenobarbital is a common drug used to manage epilepsy in goats. However, the recommended dose and dosing frequency are based on studies in dogs and horses. Studies describing the pharmacokinetics of phenobarbital when administered orally and assessing changes in behavior with concurrent electroencephalogram (EEG) readings are warranted in goats. The objectives of this study were to determine the bioavailability of orally administered phenobarbital and determine the effect of phenobarbital on brain activity using EEG in healthy goats. A cross-over design with 8 non-pregnant goats was performed. The goats were administered phenobarbital intravenously at 10 mg/kg, followed by a 2 week wash out period, and then administered phenobarbital, orally, at 10 mg/kg. Plasma sample determination of phenobarbital concentrations were collected at 13 time points. Continuous EEG readings with simultaneous video recording for 12 h was performed to determine the state of vigilance using a behavior scoring system prior to and after phenobarbital administration. Bioavailability of phenobarbital was 24.9%. Mean ± SD for half-life was similar between the oral (3.80 ± 0.826 h) and intravenous (4.0 ± 0.619 h) routes. Time to observed maximum concentration (T(max)), and maximum plasma concentration (C(max)) for the oral administration were 1.75 ± 0.46 h and 4,478.7 ± 962.4 ng/mL, respectively. Clearance was 152.5 ± 102.7 ml/h/kg. Area under the curve from zero to infinity (AUC(0→∞)) was 155,813 ± 218,448 and 38,763 ± 9,832 h(*)ng/mL for the intravenous and oral administration routes, respectively. Behavior score at 3 h after phenobarbital administration was different (P = 0.0002) from the score prior to administration for the oral administration route. In contrast, behavior scores before administration of phenobarbital and each time point after administration were not different (P >0.05) for the intravenous administration route or other oral administration route time points. Bioavailability of phenobarbital was poor, and the half-life was very short due to a high clearance. Doses >10 mg/kg should be considered when phenobarbital is administered orally in goats.
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spelling pubmed-70466252020-03-09 Pharmacokinetics of Intravenous and Oral Phenobarbital Sodium in Healthy Goats Yates, Liana M. Aleman, Monica Knych, Heather K. Knipe, Marguerite F. Crowe, Chelsea M. Chigerwe, Munashe Front Vet Sci Veterinary Science Phenobarbital is a common drug used to manage epilepsy in goats. However, the recommended dose and dosing frequency are based on studies in dogs and horses. Studies describing the pharmacokinetics of phenobarbital when administered orally and assessing changes in behavior with concurrent electroencephalogram (EEG) readings are warranted in goats. The objectives of this study were to determine the bioavailability of orally administered phenobarbital and determine the effect of phenobarbital on brain activity using EEG in healthy goats. A cross-over design with 8 non-pregnant goats was performed. The goats were administered phenobarbital intravenously at 10 mg/kg, followed by a 2 week wash out period, and then administered phenobarbital, orally, at 10 mg/kg. Plasma sample determination of phenobarbital concentrations were collected at 13 time points. Continuous EEG readings with simultaneous video recording for 12 h was performed to determine the state of vigilance using a behavior scoring system prior to and after phenobarbital administration. Bioavailability of phenobarbital was 24.9%. Mean ± SD for half-life was similar between the oral (3.80 ± 0.826 h) and intravenous (4.0 ± 0.619 h) routes. Time to observed maximum concentration (T(max)), and maximum plasma concentration (C(max)) for the oral administration were 1.75 ± 0.46 h and 4,478.7 ± 962.4 ng/mL, respectively. Clearance was 152.5 ± 102.7 ml/h/kg. Area under the curve from zero to infinity (AUC(0→∞)) was 155,813 ± 218,448 and 38,763 ± 9,832 h(*)ng/mL for the intravenous and oral administration routes, respectively. Behavior score at 3 h after phenobarbital administration was different (P = 0.0002) from the score prior to administration for the oral administration route. In contrast, behavior scores before administration of phenobarbital and each time point after administration were not different (P >0.05) for the intravenous administration route or other oral administration route time points. Bioavailability of phenobarbital was poor, and the half-life was very short due to a high clearance. Doses >10 mg/kg should be considered when phenobarbital is administered orally in goats. Frontiers Media S.A. 2020-02-21 /pmc/articles/PMC7046625/ /pubmed/32154280 http://dx.doi.org/10.3389/fvets.2020.00086 Text en Copyright © 2020 Yates, Aleman, Knych, Knipe, Crowe and Chigerwe. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Veterinary Science
Yates, Liana M.
Aleman, Monica
Knych, Heather K.
Knipe, Marguerite F.
Crowe, Chelsea M.
Chigerwe, Munashe
Pharmacokinetics of Intravenous and Oral Phenobarbital Sodium in Healthy Goats
title Pharmacokinetics of Intravenous and Oral Phenobarbital Sodium in Healthy Goats
title_full Pharmacokinetics of Intravenous and Oral Phenobarbital Sodium in Healthy Goats
title_fullStr Pharmacokinetics of Intravenous and Oral Phenobarbital Sodium in Healthy Goats
title_full_unstemmed Pharmacokinetics of Intravenous and Oral Phenobarbital Sodium in Healthy Goats
title_short Pharmacokinetics of Intravenous and Oral Phenobarbital Sodium in Healthy Goats
title_sort pharmacokinetics of intravenous and oral phenobarbital sodium in healthy goats
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046625/
https://www.ncbi.nlm.nih.gov/pubmed/32154280
http://dx.doi.org/10.3389/fvets.2020.00086
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