title: Effect of polymorphisms in CYP3A4, PPARA, NR1I2, NFKB1, ABCG2 and SLCO1B1 on the pharmacokinetics of lovastatin in healthy Chinese volunteers.
abstract: OBJECTIVE
  This study examined whether gene polymorphisms (CYP3A4, ABCG2, SLCO1B1, NR1I2, PPARA and NFKB1) influenced the pharmacokinetics of lovastatin in Chinese healthy subjects.
  
  
  METHODS
  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 Cmaxof 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.
  
  
  CONCLUSIONS
  Gene polymorphisms of PPARA, SLCO1B1 and NFKB1 affected the pharmacokinetics of lovastatin.
authors.affiliation: Department of Pharmacy, Shengjing Hospital of China Medical University, No. 36 Sanhao Street Heping District, Shenyang 110004, China.|Department of Pharmacology, Shenyang Pharmaceutical University, No. 103 Wenhua Road Shenhe District, Shenyang 110016, China.
authors.forename: Guilian
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Shengjing Hospital of China Medical University, No. 36 Sanhao Street Heping District, Shenyang 110004, China.|Department of Clinical Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road Shenhe District, Shenyang 110016, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.affiliation: Laboratory of Clinical Pharmacokinetics of TCM, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, No. 33 Beiling Street Huanggu District, Shenyang 110032, China.
authors.forename: Xiujun
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Shengjing Hospital of China Medical University, No. 36 Sanhao Street Heping District, Shenyang 110004, China.
authors.forename: Guofei
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Shengjing Hospital of China Medical University, No. 36 Sanhao Street Heping District, Shenyang 110004, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Research Center for Drug Metabolism, College of Life Science, Jilin University, No. 2699 Qianjin Street Chaoyang District, Changchun 130021, China.
authors.forename: Jingkai
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Pharmacy, Shengjing Hospital of China Medical University, No. 36 Sanhao Street Heping District, Shenyang 110004, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D064368:Healthy Volunteers; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics; D008148:Lovastatin / Q000097:blood / Q000493:pharmacokinetics*; D052002:NF-kappa B p50 Subunit / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D047493:PPAR alpha / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; C000625852:NR1I2 protein, human; D009363:Neoplasm Proteins; D047493:PPAR alpha; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; C503999:SLCO1B1 protein, human; D008148:Lovastatin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
keywords: ABCG2; CYP3A4; NFKB1; NR1I2; PPARA; SLCO1B1; lovastatin; lovastatin acid; pharmacokinetics