Effect of polymorphisms in CYP3A4, PPARA, NR1I2, NFKB1, ABCG2 and SLCO1B1 on the pharmacokinetics of lovastatin in healthy Chinese volunteers. (January 2017)

• Record Type: Journal Article
• Authors: Zhao, Guilian; Liu, Mei; Wu, Xiujun; Li, Guofei; Qiu, Feng; Gu, Jingkai; Zhao, Limei
• Is Part Of: Pharmacogenomics. Volume 18:Number 1(2017)
• Page Start: 65
• Page End: 75
• Publication Date: 2017-01
• Subjects: ABCG2 -- CYP3A4 -- lovastatin -- lovastatin acid -- NFKB1 -- NR1I2 -- pharmacokinetics -- PPARA -- SLCO1B1; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.16.31
• Languages: English
• ISSNs: 1462-2416

Abstract

Aim: This study examined whether gene polymorphisms ( CYP3A4, ABCG2, SLCO1B1, NR1I2, PPARA and NFKB1 ) influenced the pharmacokinetics of lovastatin in Chinese healthy subjects.Patients & method: Plasma concentrations of lovastatin and lovastatin acid were quantified using LC/MS/MS.Results: PPARA c.208+3819 G allele carriers had approximately twofold higher AUC0-∞ and Cmax of lovastatin than wild-type ( PPARA c.208+3819 AA) subjects. After adjustment for the PPARA variants, subjects with the SLCO1B1 521TT genotype had approximately 50% lower AUC0-∞ of lovastatin acid than those with 521TC/CC genotypes, while the AUC0-∞ of lovastatin lactone in NFKB1 -94 DD wild-type carriers was twofold higher than in mutant homozygotes carriers.Conclusion: Gene polymorphisms of PPARA, SLCO1B1 and NFKB1 affected the pharmacokinetics of lovastatin.