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The influence of CYP 3A5*3 and BCRPC 421A genetic polymorphisms on the pharmacokinetics of felodipine in healthy Chinese volunteers
Author(s) -
Xiang Q.,
Li C.,
Zhao X.,
Cui Y. M.
Publication year - 2017
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12505
Subject(s) - felodipine , pharmacokinetics , pharmacology , pharmacogenetics , cyp2d6 , cyp2c19 , population , cyp3a , cyp3a5 , medicine , drug metabolism , polymorphism (computer science) , metabolism , genotype , chemistry , cytochrome p450 , drug , blood pressure , biochemistry , gene , environmental health
Summary What is known and objective The role of CYP 3A5 in drug metabolism has been receiving attention because CYP 3A5 may be more involved in the metabolism of CYP 3A substrates in vivo than previously thought. The polymorphism of transporters, such as P‐gp (P‐glycoprotein) and breast cancer‐related protein ( BCRP ), influences the metabolism of these substrates, and felodipine is a substrate of P‐gp. The aim of this study was to evaluate the pharmacogenetic variability in the disposition of felodipine in healthy Chinese subjects. Methods A single dose of 5 mg felodipine was orally administered to 45 healthy Chinese subjects. The serum concentration of felodipine was measured by using LC / MS / MS . We detected the SNP s of cytochromes P450 enzymes and transporters, which play vital roles in drug metabolism and have a high frequency of mutation in Chinese population. Results and discussion The area under the plasma concentration–time curve ( AUC ) within the time points 0 to 72 h ( AUC (0–72) ) after felodipine administration was significantly higher in subjects possessing the BCRP 421 AA alleles than in those with the BCRP 421 CC or CA genotype (P = 0·034). The subjects with CYP 3A5*3/*3 ( n = 27) had higher felodipine exposure than CYP 3A5*1/*3 ( n = 15) (P = 0·035). What is new and conclusion This study showed that the genetic polymorphisms of CYP 3A5*3 and BCRPC 421A might explain the variability in the pharmacokinetics of felodipine in the Chinese population.