Guilian Zhao1,2, Mei Liu1,3, Xiujun Wu4, Guofei Li1, Feng Qiu1, Jingkai Gu5, Limei Zhao1. 1. Department of Pharmacy, Shengjing Hospital of China Medical University, No. 36 Sanhao Street Heping District, Shenyang 110004, China. 2. Department of Pharmacology, Shenyang Pharmaceutical University, No. 103 Wenhua Road Shenhe District, Shenyang 110016, China. 3. Department of Clinical Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road Shenhe District, Shenyang 110016, China. 4. Laboratory of Clinical Pharmacokinetics of TCM, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, No. 33 Beiling Street Huanggu District, Shenyang 110032, China. 5. Research Center for Drug Metabolism, College of Life Science, Jilin University, No. 2699 Qianjin Street Chaoyang District, Changchun 130021, China.
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.
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.