title: Impact of CYP2D6 polymorphisms on the pharmacokinetics of lovastatin in Chinese subjects.
abstract: OBJECTIVE
  Although CYP3A4/5 enzymes play the predominant role in the metabolism of simvastatin and lovastatin, polymorphisms in CYP2D6 were reported to be associated with the cholesterol-lowering effect and/or tolerability of simvastatin. This study was performed to examine whether common CYP2D6 polymorphisms affect the pharmacokinetics of lovastatin, which is taken as the inactive prodrug lovastatin lactone and converted to active lovastatin acid.
  
  
  METHODS
  A single-dose pharmacokinetic study was performed with lovastatin in 23 Chinese healthy male subjects. Plasma concentrations of lovastatin lactone and acid were determined by an LC-MS-MS method in samples collected over 24 h after single oral doses of 40-mg lovastatin.
  
  
  RESULTS
  Compared with the CYP2D6 wt/wt group, the area under the plasma concentration-time curve (AUC(0-∞)) values for lovastatin lactone increased (P < 0.01) by average ratios (95% CI) of 1.57 (1.01-2.45), 2.11 (1.36-3.29), 2.52 (1.47-4.32), and 5.84 (3.16-10.78) in the wt/*10, *10/*10, *10/*5, and *5/*5 groups, and the values of lovastatin lactone plasma clearance (CL/F) were reduced on average (95% CI) by 40.4% (10.2-60.5%), 53.1% (29.3-68.9%), 63.8% (40.2-78.1%) and 84.2% (72.1-91.1%) in these genotype groups respectively. The pharmacokinetics of lovastatin acid did not differ among the genotype groups.
  
  
  CONCLUSIONS
  This study demonstrates that CYP2D6 polymorphisms appeared to influence the disposition of lovastatin lactone in these subjects.
authors.affiliation: School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
authors.forename: Ophelia Qi Ping
authors.initials: OQ
authors.lastname: Yin
authors.forename: Valiant Wah Lun
authors.initials: VW
authors.lastname: Mak
authors.forename: Miao
authors.initials: M
authors.lastname: Hu
authors.forename: Benny Siu Pong
authors.initials: BS
authors.lastname: Fok
authors.forename: Moses Sing Sum
authors.initials: MS
authors.lastname: Chow
authors.forename: Brian
authors.initials: B
authors.lastname: Tomlinson
mesh_terms: D000328:Adult; D000483:Alleles; D000924:Anticholesteremic Agents / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D044466:Asian People; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006207:Half-Life; D006801:Humans; D008148:Lovastatin / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D000924:Anticholesteremic Agents; D008148:Lovastatin; D019389:Cytochrome P-450 CYP2D6