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ID 58231
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Author
Matsumoto, Jun Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate ORCID Kaken ID researchmap
San, Su Nwe Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
Fujiyoshi, Masachika Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate
Kawauchi, Ayano Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
Chiba, Natsumi Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
Tagai, Ran Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
Sanbe, Ryoko Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
Yanaka, Shiho Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
Sakaue, Hiroaki Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
Kato, Yoshinori Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
Nakamura, Hiroyoshi Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
Yamada, Harumi Department of Pharmacokinetics, Pharmaceutical Sciences, International University of Health and Welfare
Ariyoshi, Noritaka Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama University Kaken ID researchmap
Abstract
Direct-acting antivirals, asunaprevir (ASV), daclatasvir (DCV), and beclabuvir (BCV) are known to be mainly metabolized by CYP3A enzymes; however, the differences in the detailed metabolic activities of CYP3A4 and CYP3A5 on these drugs are not well clarified. The aim of the present study was to elucidate the relative contributions of CYP3A4 and CYP3A5 to the metabolism of ASV, DCV, and BCV, as well as the effect of CYP3A5*3 genetic variant in vitro. The amount of each drug and their major metabolites were determined using LC-MS/MS. Recombinant CYP3As and CYP3A5*3-genotyped human liver microsomes (CYP3A5 expressers or non-expressers) were used for the determination of their metabolic activities. The contribution of CYP3A5 to ASV metabolism was considerable compared to that of CYP3A4. Consistently, ASV metabolic activity in CYP3A5 expressers was higher than those in CYP3A5 non-expresser. Moreover, CYP3A5 expression level was significantly correlated with ASV metabolism. In contrast, these observations were not found in DCV and BCV metabolism. To our knowledge, this is the first study to directly demonstrate the effect of CYP3A5*3 genetic variants on the metabolism of ASV. The findings of the present study may provide basic information on ASV, DCV, and BCV metabolisms.
Keywords
Genetic markers
Haplotypes
Published Date
2019-10-23
Publication Title
Journal of Human Genetics
Volume
volume65
Publisher
Japan Society of Human Genetics
Start Page
143
End Page
153
ISSN
1434-5161
NCID
AA11206160
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
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DOI
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Related Url
isVersionOf https://doi.org/10.1038/s10038-019-0685-2
Funder Name
Ministry of Education, Culture, Sports, Science and Technology
助成番号
16K18955