Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hwang, Sejung, Ko, Jae-Wook, Lee, Heechan, Kim, Seokuee, Kim, Bongtae, Song, Geun Seog, Kim, Jungryul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
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
_version_ 1784607799447126016
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
work_keys_str_mv AT hwangsejung coadministrationofvonoprazannottegoprazanaffectsthepharmacokineticsofatorvastatininhealthymalesubjects
AT kojaewook coadministrationofvonoprazannottegoprazanaffectsthepharmacokineticsofatorvastatininhealthymalesubjects
AT leeheechan coadministrationofvonoprazannottegoprazanaffectsthepharmacokineticsofatorvastatininhealthymalesubjects
AT kimseokuee coadministrationofvonoprazannottegoprazanaffectsthepharmacokineticsofatorvastatininhealthymalesubjects
AT kimbongtae coadministrationofvonoprazannottegoprazanaffectsthepharmacokineticsofatorvastatininhealthymalesubjects
AT songgeunseog coadministrationofvonoprazannottegoprazanaffectsthepharmacokineticsofatorvastatininhealthymalesubjects
AT kimjungryul coadministrationofvonoprazannottegoprazanaffectsthepharmacokineticsofatorvastatininhealthymalesubjects