Effect of polymorphisms in CYP3A4, PPARA, NR1I2, NFKB1, ABCG2 and SLCO1B1 on the pharmacokinetics of lovastatin in healthy Chinese volunteers.
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.
['Zhao|Guilian|G|', 'Liu|Mei|M|', 'Wu|Xiujun|X|', 'Li|Guofei|G|', 'Qiu|Feng|F|', 'Gu|Jingkai|J|', 'Zhao|Limei|L|']
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 D044466:Asians D051544:Cytochrome P-450 CYP3A D064368:Healthy Volunteers D006801:Humans D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors D027381:Liver-Specific Organic Anion Transporter 1 D008148:Lovastatin D052002:NF-kappa B p50 Subunit D009363:Neoplasm Proteins D047493:PPAR alpha D020641:Polymorphism, Single Nucleotide D000077297:Pregnane X Receptor D011987:Receptors, Steroid
CYP3A4 PPARA NR1I2 NFKB1 ABCG2 SLCO1B1 pharmacokinetics lovastatin lovastatin acid