Effects of cytochrome P450 oxidoreductase genotypes on the pharmacokinetics of amlodipine in healthy Korean subjects
- 주제(키워드) amlodipine , CYP3A , pharmacokinetics , POR polymorphism
- 주제(기타) Genetics & Heredity
- 설명문(일반) [Han, Ji Min; Yee, Jeong; Gwak, Hye Sun] Ewha Womans Univ, Coll Pharm, 52 Ewhayeodae Gil, Seoul 03760, South Korea; [Han, Ji Min; Yee, Jeong; Gwak, Hye Sun] Ewha Womans Univ, Grad Sch Pharmaceut Sci, 52 Ewhayeodae Gil, Seoul 03760, South Korea; [Chung, Jee Eun] Hanyang Univ, Coll Pharm, Ansan, South Korea; [Lee, Kyung Eun] Chungbuk Natl Univ, Coll Pharm, Cheongju, South Korea; [Park, Kyungsoo] Yonsei Univ, Dept Pharmacol, Coll Med, Seoul, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Green Published, gold
- 발행기관 WILEY
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000168899
- 본문언어 영어
- Published As https://dx.doi.org/10.1002/mgg3.1201
- PubMed https://pubmed.ncbi.nlm.nih.gov/32134573
초록/요약
Background The aim of this study was to investigate the effects of P450 oxidoreductase (POR) genetic polymorphisms on the pharmacokinetic parameters of amlodipine. Methods After a single 10-mg dose of amlodipine administration, 25 healthy male subjects completed genotyping for 12 single nucleotide polymorphisms (SNPs) of the POR genes, cytochrome P450 (CYP)3A4 g.25343G>A (CYP3A4*1G), and CYP3A5 g.12083G>A (CYP3A5*3). Stratified analysis and in silico analysis to predict the possible effects of given variants on splicing were performed. Results The maximum blood concentration (C-max) of amlodipine in carriers of g.57332T>C and g.56551G>A SNPs of the POR gene was statistically significantly different. In addition, T-allele carriers of g.57332T>C had a 21% higher C-max than those with the CC genotype (p = .007). Subjects who carried the wild-type g.56551G>A allele also had a 1.12-fold significantly higher C-max than subjects with mutant-type homozygous carriers (p = .033). In stratified analyses, g.57332T>C was significantly associated with a 1.3-fold increase in C-max value in T-allele carriers compared with subjects with the CC genotype in CYP3A4 and CYP3A5 expressers. POR g.57332T>C increased the score above the threshold in both ESEfinder 3.0 and HSF 3.1. Conclusion This study identified a novel SNP of the POR gene, which affected amlodipine metabolism and may reduce interindividual variation in responses to amlodipine.
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