Effects of cytochrome P450 oxidoreductase genotypes on the pharmacokinetics of amlodipine in healthy Korean subjects

Ji Min Han, Jeong Yee, Jee Eun Chung, Kyung Eun Lee, Kyungsoo Park, Hye Sun Gwak

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 (Cmax) 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 Cmax 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 Cmax 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 Cmax 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.

Original languageEnglish
Article numbere1201
JournalMolecular Genetics and Genomic Medicine
Volume8
Issue number5
DOIs
StatePublished - 1 May 2020

Keywords

  • CYP3A
  • POR polymorphism
  • amlodipine
  • pharmacokinetics

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