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...

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Autores principales:	Sejung Hwang, Jae-Wook Ko, Heechan Lee, Seokuee Kim, Bongtae Kim, Geun Seog Song, Jungryul Kim
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	drug interactions tegoprazan vonoprazan cytochrome P450 (CYP) pharmacokinetics potassium-competitive acid blocker Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/0ac707387ef145729c9ab9d63d8e7a73
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spelling	oai:doaj.org-article:0ac707387ef145729c9ab9d63d8e7a732021-11-11T16:30:12ZCo-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects1663-981210.3389/fphar.2021.754849https://doaj.org/article/0ac707387ef145729c9ab9d63d8e7a732021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.754849/fullhttps://doaj.org/toc/1663-9812Potassium-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.Sejung HwangJae-Wook KoHeechan LeeSeokuee KimBongtae KimGeun Seog SongJungryul KimJungryul KimFrontiers Media S.A.articledrug interactionstegoprazanvonoprazancytochrome P450 (CYP)pharmacokineticspotassium-competitive acid blockerTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	drug interactions tegoprazan vonoprazan cytochrome P450 (CYP) pharmacokinetics potassium-competitive acid blocker Therapeutics. Pharmacology RM1-950
spellingShingle	drug interactions tegoprazan vonoprazan cytochrome P450 (CYP) pharmacokinetics potassium-competitive acid blocker Therapeutics. Pharmacology RM1-950 Sejung Hwang Jae-Wook Ko Heechan Lee Seokuee Kim Bongtae Kim Geun Seog Song Jungryul Kim Jungryul Kim Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects
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	article
author	Sejung Hwang Jae-Wook Ko Heechan Lee Seokuee Kim Bongtae Kim Geun Seog Song Jungryul Kim Jungryul Kim
author_facet	Sejung Hwang Jae-Wook Ko Heechan Lee Seokuee Kim Bongtae Kim Geun Seog Song Jungryul Kim Jungryul Kim
author_sort	Sejung Hwang
title	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_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_sort	co-administration of vonoprazan, not tegoprazan, affects the pharmacokinetics of atorvastatin in healthy male subjects
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0ac707387ef145729c9ab9d63d8e7a73
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Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects

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