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Effects of Voriconazole on the Pharmacokinetics of Vonoprazan in Rats

PURPOSE: The purpose of this study was to examine the effects of voriconazole on the pharmacokinetics of vonoprazan. METHODS: Fifteen Sprague-Dawley rats were randomly divided into three groups: five rats in each group, including control group, single-dose group (a single dose of 30 mg/kg of voricon...

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Autores principales: Shen, Jiquan, Wang, Bo, Wang, Shuanghu, Chen, Feifei, Meng, Deru, Jiang, Hui, Zhou, Yunfang, Geng, Peiwu, Zhou, Quan, Liu, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280087/
https://www.ncbi.nlm.nih.gov/pubmed/32581516
http://dx.doi.org/10.2147/DDDT.S255427
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author Shen, Jiquan
Wang, Bo
Wang, Shuanghu
Chen, Feifei
Meng, Deru
Jiang, Hui
Zhou, Yunfang
Geng, Peiwu
Zhou, Quan
Liu, Bin
author_facet Shen, Jiquan
Wang, Bo
Wang, Shuanghu
Chen, Feifei
Meng, Deru
Jiang, Hui
Zhou, Yunfang
Geng, Peiwu
Zhou, Quan
Liu, Bin
author_sort Shen, Jiquan
collection PubMed
description PURPOSE: The purpose of this study was to examine the effects of voriconazole on the pharmacokinetics of vonoprazan. METHODS: Fifteen Sprague-Dawley rats were randomly divided into three groups: five rats in each group, including control group, single-dose group (a single dose of 30 mg/kg of voriconazole), and multiple-dose group (multiple doses of 30 mg/(kg•day) per dose of voriconazole). Each group of rats was given an oral dose of 10 mg/kg vonoprazan 30 min after the administration of voriconazole or vehicle. After the oral administration of vonoprazan, 50 µL of blood was collected into 1.5-mL heparinized tubes via the caudal vein. The concentration of vonoprazan in plasma was quantified by ultra-performance liquid chromatography/tandem mass spectrometry. Both in vitro effects of voriconazole on vonoprazan and the mechanism of the observed inhibition were studied in rat liver microsomes. RESULTS: When orally administered, voriconazole increased the area under the plasma concentration–time curve (AUC), prolonged the elimination half-life (t(1/2)), and decreased the clearance (CL) of vonoprazan; there was no significant difference between the single-dose and multiple-dose groups. Voriconazole inhibited the metabolism of vonoprazan at an IC50 of 2.93 μM and showed mixed inhibition. The results of the in vivo experiments were consistent with those of the in vitro experiments. CONCLUSION: Our findings provide the evidence of drug–drug interactions between voriconazole and vonoprazan that could occur with pre-administration of voriconazole. Thus, clinicians should pay attention to the resulting changes in pharmacokinetic parameters and accordingly, adjust the dose of vonoprazan in clinical settings.
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spelling pubmed-72800872020-06-23 Effects of Voriconazole on the Pharmacokinetics of Vonoprazan in Rats Shen, Jiquan Wang, Bo Wang, Shuanghu Chen, Feifei Meng, Deru Jiang, Hui Zhou, Yunfang Geng, Peiwu Zhou, Quan Liu, Bin Drug Des Devel Ther Original Research PURPOSE: The purpose of this study was to examine the effects of voriconazole on the pharmacokinetics of vonoprazan. METHODS: Fifteen Sprague-Dawley rats were randomly divided into three groups: five rats in each group, including control group, single-dose group (a single dose of 30 mg/kg of voriconazole), and multiple-dose group (multiple doses of 30 mg/(kg•day) per dose of voriconazole). Each group of rats was given an oral dose of 10 mg/kg vonoprazan 30 min after the administration of voriconazole or vehicle. After the oral administration of vonoprazan, 50 µL of blood was collected into 1.5-mL heparinized tubes via the caudal vein. The concentration of vonoprazan in plasma was quantified by ultra-performance liquid chromatography/tandem mass spectrometry. Both in vitro effects of voriconazole on vonoprazan and the mechanism of the observed inhibition were studied in rat liver microsomes. RESULTS: When orally administered, voriconazole increased the area under the plasma concentration–time curve (AUC), prolonged the elimination half-life (t(1/2)), and decreased the clearance (CL) of vonoprazan; there was no significant difference between the single-dose and multiple-dose groups. Voriconazole inhibited the metabolism of vonoprazan at an IC50 of 2.93 μM and showed mixed inhibition. The results of the in vivo experiments were consistent with those of the in vitro experiments. CONCLUSION: Our findings provide the evidence of drug–drug interactions between voriconazole and vonoprazan that could occur with pre-administration of voriconazole. Thus, clinicians should pay attention to the resulting changes in pharmacokinetic parameters and accordingly, adjust the dose of vonoprazan in clinical settings. Dove 2020-06-04 /pmc/articles/PMC7280087/ /pubmed/32581516 http://dx.doi.org/10.2147/DDDT.S255427 Text en © 2020 Shen et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Shen, Jiquan
Wang, Bo
Wang, Shuanghu
Chen, Feifei
Meng, Deru
Jiang, Hui
Zhou, Yunfang
Geng, Peiwu
Zhou, Quan
Liu, Bin
Effects of Voriconazole on the Pharmacokinetics of Vonoprazan in Rats
title Effects of Voriconazole on the Pharmacokinetics of Vonoprazan in Rats
title_full Effects of Voriconazole on the Pharmacokinetics of Vonoprazan in Rats
title_fullStr Effects of Voriconazole on the Pharmacokinetics of Vonoprazan in Rats
title_full_unstemmed Effects of Voriconazole on the Pharmacokinetics of Vonoprazan in Rats
title_short Effects of Voriconazole on the Pharmacokinetics of Vonoprazan in Rats
title_sort effects of voriconazole on the pharmacokinetics of vonoprazan in rats
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280087/
https://www.ncbi.nlm.nih.gov/pubmed/32581516
http://dx.doi.org/10.2147/DDDT.S255427
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