Effects of cytochrome P450 oxidoreductase genotypes on the pharmacokinetics of amlodipine in healthy Korean subjects
- Title
- Effects of cytochrome P450 oxidoreductase genotypes on the pharmacokinetics of amlodipine in healthy Korean subjects
- Author
- 정지은
- Issue Date
- 2020-05
- Publisher
- WILEY
- Citation
- MOLECULAR GENETICS & GENOMIC MEDICINE, v. 8, Issue. 5, Page. 1201-1211
- Abstract
- 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.
- URI
- https://onlinelibrary.wiley.com/doi/10.1002/mgg3.1201https://repository.hanyang.ac.kr/handle/20.500.11754/164445
- ISSN
- 2324-9269
- DOI
- 10.1002/mgg3.1201
- Appears in Collections:
- COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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