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Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects
Potassium-competitive acid blocker is a new class of drugs inhibiting gastric acid. It is controversial that vonoprazan showed the inhibitory activities of cytochrome P450 3A4. This study aimed to evaluate the pharmacokinetics (PK) of atorvastatin and safety when atorvastatin was administered alone...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632694/ https://www.ncbi.nlm.nih.gov/pubmed/34867368 http://dx.doi.org/10.3389/fphar.2021.754849 |
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author | Hwang, Sejung Ko, Jae-Wook Lee, Heechan Kim, Seokuee Kim, Bongtae Song, Geun Seog Kim, Jungryul |
author_facet | Hwang, Sejung Ko, Jae-Wook Lee, Heechan Kim, Seokuee Kim, Bongtae Song, Geun Seog Kim, Jungryul |
author_sort | Hwang, Sejung |
collection | PubMed |
description | Potassium-competitive acid blocker is a new class of drugs inhibiting gastric acid. It is controversial that vonoprazan showed the inhibitory activities of cytochrome P450 3A4. This study aimed to evaluate the pharmacokinetics (PK) of atorvastatin and safety when atorvastatin was administered alone and co-administered with vonoprazan or tegoprazan. An open-label, multiple-dose, 3-intervention, 4-sequence, 4-period, partial replicate crossover study was conducted, and three interventions were; one is orally administered atorvastatin 40 mg alone once daily for 7 days, another is atorvastatin co-administered with vonoprazan 20 mg, and the other is atorvastatin co-administered with tegoprazan 50 mg. PK blood samples were collected up to 24 h after the last dose, and PK parameters for atorvastatin, 2-hydroxyatorvastatin and atorvastatin lactone were estimated by a non-compartmental method. Safety was evaluated, including adverse events and clinical laboratory tests. A total of 28 subjects completed the study. When atorvastatin was co-administered with vonoprazan, the systemic exposures of atorvastatin and atorvastatin lactone significantly increased, and the metabolic ratio of 2-hydroxyatorvastatin significantly decreased. Hypergastrinemia only occurred when atorvastatin was co-administered with vonoprazan. However, the plasma concentration profiles of atorvastatin, 2-hydroxyatorvastatin and atorvastatin lactone were similar when atorvastatin was administered alone or co-administered with tegoprazan. In conclusion, after multiple doses of atorvastatin co-administered with vonoprazan in healthy subjects, the systemic exposure of atorvastatin and the incidence of hypergastrinemia increased. With tegoprazan, however, those interactions were not observed. |
format | Online Article Text |
id | pubmed-8632694 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86326942021-12-02 Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects Hwang, Sejung Ko, Jae-Wook Lee, Heechan Kim, Seokuee Kim, Bongtae Song, Geun Seog Kim, Jungryul Front Pharmacol Pharmacology Potassium-competitive acid blocker is a new class of drugs inhibiting gastric acid. It is controversial that vonoprazan showed the inhibitory activities of cytochrome P450 3A4. This study aimed to evaluate the pharmacokinetics (PK) of atorvastatin and safety when atorvastatin was administered alone and co-administered with vonoprazan or tegoprazan. An open-label, multiple-dose, 3-intervention, 4-sequence, 4-period, partial replicate crossover study was conducted, and three interventions were; one is orally administered atorvastatin 40 mg alone once daily for 7 days, another is atorvastatin co-administered with vonoprazan 20 mg, and the other is atorvastatin co-administered with tegoprazan 50 mg. PK blood samples were collected up to 24 h after the last dose, and PK parameters for atorvastatin, 2-hydroxyatorvastatin and atorvastatin lactone were estimated by a non-compartmental method. Safety was evaluated, including adverse events and clinical laboratory tests. A total of 28 subjects completed the study. When atorvastatin was co-administered with vonoprazan, the systemic exposures of atorvastatin and atorvastatin lactone significantly increased, and the metabolic ratio of 2-hydroxyatorvastatin significantly decreased. Hypergastrinemia only occurred when atorvastatin was co-administered with vonoprazan. However, the plasma concentration profiles of atorvastatin, 2-hydroxyatorvastatin and atorvastatin lactone were similar when atorvastatin was administered alone or co-administered with tegoprazan. In conclusion, after multiple doses of atorvastatin co-administered with vonoprazan in healthy subjects, the systemic exposure of atorvastatin and the incidence of hypergastrinemia increased. With tegoprazan, however, those interactions were not observed. Frontiers Media S.A. 2021-11-11 /pmc/articles/PMC8632694/ /pubmed/34867368 http://dx.doi.org/10.3389/fphar.2021.754849 Text en Copyright © 2021 Hwang, Ko, Lee, Kim, Kim, Song and Kim. https://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 | Pharmacology Hwang, Sejung Ko, Jae-Wook Lee, Heechan Kim, Seokuee Kim, Bongtae Song, Geun Seog Kim, Jungryul Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects |
title | Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects |
title_full | Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects |
title_fullStr | Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects |
title_full_unstemmed | Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects |
title_short | Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects |
title_sort | co-administration of vonoprazan, not tegoprazan, affects the pharmacokinetics of atorvastatin in healthy male subjects |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632694/ https://www.ncbi.nlm.nih.gov/pubmed/34867368 http://dx.doi.org/10.3389/fphar.2021.754849 |
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