ID | 58231 |
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Author |
Matsumoto, Jun
Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate
ORCID
Kaken ID
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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
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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.
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Keywords | Genetic markers
Haplotypes
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Published Date | 2019-10-23
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Publication Title |
Journal of Human Genetics
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Volume | volume65
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Publisher | Japan Society of Human Genetics
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Start Page | 143
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End Page | 153
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ISSN | 1434-5161
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NCID | AA11206160
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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File Version | author
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Related Url | isVersionOf https://doi.org/10.1038/s10038-019-0685-2
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Funder Name |
Ministry of Education, Culture, Sports, Science and Technology
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助成番号 | 16K18955
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