Cargando…

The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers

The dosing regimen of prasugrel adjusted for Japanese patients was compared with that of clopidogrel by analyzing the pharmacokinetics and pharmacodynamics in 40 healthy Japanese subjects in a randomized, single‐blind crossover study. In period 1, the subjects received either 300 mg clopidogrel or 2...

Descripción completa

Detalles Bibliográficos
Autores principales: Umemura, Kazuo, Iwaki, Takayuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5132138/
https://www.ncbi.nlm.nih.gov/pubmed/27514617
http://dx.doi.org/10.1002/cpdd.259
_version_ 1782471011465166848
author Umemura, Kazuo
Iwaki, Takayuki
author_facet Umemura, Kazuo
Iwaki, Takayuki
author_sort Umemura, Kazuo
collection PubMed
description The dosing regimen of prasugrel adjusted for Japanese patients was compared with that of clopidogrel by analyzing the pharmacokinetics and pharmacodynamics in 40 healthy Japanese subjects in a randomized, single‐blind crossover study. In period 1, the subjects received either 300 mg clopidogrel or 20 mg prasugrel; after a >2‐week interval (period 2), the drug was switched. Blood samples of 36 of the 40 subjects were collected for analysis of pharmacokinetics, pharmacodynamics, and CYP2C19 genotypes. The plasma concentration of the active metabolite of prasugrel increased rapidly and reached its peak 30 minutes postadministration, whereas that of the active metabolite of clopidogrel reached its peak 1 hour postadministration. The mean AUC and C(max) of the active metabolite of clopidogrel, but not those of prasugrel, were CYP2C19 genotype dependent. Prasugrel rapidly inhibited platelet aggregation, reaching its maximum effect 1 hour postadministration. Clopidogrel, on the other hand, showed maximum inhibition 2 hours postadministration. Platelet aggregation inhibition by clopidogrel was significantly lower in the poor‐metabolizer subjects than in the extensive‐metabolizer subjects. Overall, prasugrel inhibited platelet aggregation more rapidly and more effectively in healthy Japanese subjects than was observed for clopidogrel.
format Online
Article
Text
id pubmed-5132138
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-51321382016-12-02 The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers Umemura, Kazuo Iwaki, Takayuki Clin Pharmacol Drug Dev Articles The dosing regimen of prasugrel adjusted for Japanese patients was compared with that of clopidogrel by analyzing the pharmacokinetics and pharmacodynamics in 40 healthy Japanese subjects in a randomized, single‐blind crossover study. In period 1, the subjects received either 300 mg clopidogrel or 20 mg prasugrel; after a >2‐week interval (period 2), the drug was switched. Blood samples of 36 of the 40 subjects were collected for analysis of pharmacokinetics, pharmacodynamics, and CYP2C19 genotypes. The plasma concentration of the active metabolite of prasugrel increased rapidly and reached its peak 30 minutes postadministration, whereas that of the active metabolite of clopidogrel reached its peak 1 hour postadministration. The mean AUC and C(max) of the active metabolite of clopidogrel, but not those of prasugrel, were CYP2C19 genotype dependent. Prasugrel rapidly inhibited platelet aggregation, reaching its maximum effect 1 hour postadministration. Clopidogrel, on the other hand, showed maximum inhibition 2 hours postadministration. Platelet aggregation inhibition by clopidogrel was significantly lower in the poor‐metabolizer subjects than in the extensive‐metabolizer subjects. Overall, prasugrel inhibited platelet aggregation more rapidly and more effectively in healthy Japanese subjects than was observed for clopidogrel. John Wiley and Sons Inc. 2016-04-25 2016 /pmc/articles/PMC5132138/ /pubmed/27514617 http://dx.doi.org/10.1002/cpdd.259 Text en © 2016, The Authors. Clinical Pharmacology in Drug Development Published by The American College of Clinical Pharmacology This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Articles
Umemura, Kazuo
Iwaki, Takayuki
The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers
title The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers
title_full The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers
title_fullStr The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers
title_full_unstemmed The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers
title_short The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy Japanese Volunteers
title_sort pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in healthy japanese volunteers
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5132138/
https://www.ncbi.nlm.nih.gov/pubmed/27514617
http://dx.doi.org/10.1002/cpdd.259
work_keys_str_mv AT umemurakazuo thepharmacokineticsandpharmacodynamicsofprasugrelandclopidogrelinhealthyjapanesevolunteers
AT iwakitakayuki thepharmacokineticsandpharmacodynamicsofprasugrelandclopidogrelinhealthyjapanesevolunteers
AT umemurakazuo pharmacokineticsandpharmacodynamicsofprasugrelandclopidogrelinhealthyjapanesevolunteers
AT iwakitakayuki pharmacokineticsandpharmacodynamicsofprasugrelandclopidogrelinhealthyjapanesevolunteers