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Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration

Background: Neonatal calves are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for potential anti-ulcerative therapies, such as pantoprazole, in ruminant species. Objective: The study objectives were to estimate plasma pharmacokinetic parameters for pantoprazo...

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Autores principales: Olivarez, Jeff D., Kreuder, Amanda J., Tatarniuk, Dane M., Wulf, Larry W., Dembek, Katarzyna A., Mochel, Jonathan P., Smith, Joe S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728716/
https://www.ncbi.nlm.nih.gov/pubmed/33330703
http://dx.doi.org/10.3389/fvets.2020.580735
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author Olivarez, Jeff D.
Kreuder, Amanda J.
Tatarniuk, Dane M.
Wulf, Larry W.
Dembek, Katarzyna A.
Mochel, Jonathan P.
Smith, Joe S.
author_facet Olivarez, Jeff D.
Kreuder, Amanda J.
Tatarniuk, Dane M.
Wulf, Larry W.
Dembek, Katarzyna A.
Mochel, Jonathan P.
Smith, Joe S.
author_sort Olivarez, Jeff D.
collection PubMed
description Background: Neonatal calves are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for potential anti-ulcerative therapies, such as pantoprazole, in ruminant species. Objective: The study objectives were to estimate plasma pharmacokinetic parameters for pantoprazole in neonatal dairy calves after intravenous (IV) administration. A secondary objective was to quantify the concentrations of pantoprazole in edible tissues after IV dosing. Methods: Pantoprazole was administered to 9 neonatal Holstein calves at a dose of 1 mg/kg IV. Plasma samples were collected over 24 h and analyzed via HPLC-MS for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Tissue samples were collected at 1, 3, and 5 days after administration and analyzed via HPLC-MS. Results: Following IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 4.46 mL/kg/min, 2.81 h, and 0.301 L/kg, respectively. The global extraction ratio was estimated at 0.053 ± 0.015. No pantoprazole was detected in the edible tissues 1, 3, or 5 days after administration. A metabolite, pantoprazole sulfone was detected in all the edible tissues 1 and 3 days after administration. Conclusion: The reported plasma clearance for pantoprazole is less than that reported for alpacas but higher than reported in foals. The elimination half-life in calves appears to be longer than observed in foals and alpacas. While pantoprazole sulfone was detected in the tissues after IV administration, further research is needed as to the metabolism and potential tissue accumulation of other pantoprazole metabolites in calves. Future pharmacodynamic studies are necessary to determine the efficacy of pantoprazole on abomasal acid suppression in calves.
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spelling pubmed-77287162020-12-15 Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration Olivarez, Jeff D. Kreuder, Amanda J. Tatarniuk, Dane M. Wulf, Larry W. Dembek, Katarzyna A. Mochel, Jonathan P. Smith, Joe S. Front Vet Sci Veterinary Science Background: Neonatal calves are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for potential anti-ulcerative therapies, such as pantoprazole, in ruminant species. Objective: The study objectives were to estimate plasma pharmacokinetic parameters for pantoprazole in neonatal dairy calves after intravenous (IV) administration. A secondary objective was to quantify the concentrations of pantoprazole in edible tissues after IV dosing. Methods: Pantoprazole was administered to 9 neonatal Holstein calves at a dose of 1 mg/kg IV. Plasma samples were collected over 24 h and analyzed via HPLC-MS for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Tissue samples were collected at 1, 3, and 5 days after administration and analyzed via HPLC-MS. Results: Following IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 4.46 mL/kg/min, 2.81 h, and 0.301 L/kg, respectively. The global extraction ratio was estimated at 0.053 ± 0.015. No pantoprazole was detected in the edible tissues 1, 3, or 5 days after administration. A metabolite, pantoprazole sulfone was detected in all the edible tissues 1 and 3 days after administration. Conclusion: The reported plasma clearance for pantoprazole is less than that reported for alpacas but higher than reported in foals. The elimination half-life in calves appears to be longer than observed in foals and alpacas. While pantoprazole sulfone was detected in the tissues after IV administration, further research is needed as to the metabolism and potential tissue accumulation of other pantoprazole metabolites in calves. Future pharmacodynamic studies are necessary to determine the efficacy of pantoprazole on abomasal acid suppression in calves. Frontiers Media S.A. 2020-11-27 /pmc/articles/PMC7728716/ /pubmed/33330703 http://dx.doi.org/10.3389/fvets.2020.580735 Text en Copyright © 2020 Olivarez, Kreuder, Tatarniuk, Wulf, Dembek, Mochel and Smith. 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
Olivarez, Jeff D.
Kreuder, Amanda J.
Tatarniuk, Dane M.
Wulf, Larry W.
Dembek, Katarzyna A.
Mochel, Jonathan P.
Smith, Joe S.
Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration
title Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration
title_full Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration
title_fullStr Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration
title_full_unstemmed Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration
title_short Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration
title_sort pharmacokinetics and tissue levels of pantoprazole in neonatal calves after intravenous administration
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728716/
https://www.ncbi.nlm.nih.gov/pubmed/33330703
http://dx.doi.org/10.3389/fvets.2020.580735
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