title: Pharmacokinetics of simvastatin lactone and its active metabolite simvastatin hydroxy acid in healthy Chinese male and female volunteers.
abstract: BACKGROUND
  Gender differences in pharmacokinetics have been reported to have important clinical consequences; however, no information about differences in the pharmacokinetics of the cholesterol-lowering drug simvastatin lactone and its metabolite, simvastatin hydroxy acid, in males and females is available.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effect of gender on the pharmacokinetics of simvastatin lactone and simvastatin hydroxy acid in healthy Han Chinese volunteers.
  
  
  METHODS
  16 healthy volunteers (8 males and 8 females) were orally administered a single dose of 40 mg simvastatin lactone after an overnight fast. Plasma was then collected 24 hours after simvastatin lactone administration. Concentrations of simvastatin lactone and simvastatin hydroxy acid were measured by high performance liquid chromatography/mass spectrometry/mass spectrometry (HPLC/MS/MS).
  
  
  RESULTS
  There were no significant associations between the pharmacokinetic parameters of simvastatin lactone and gender. For simvastatin hydroxy acid, peak plasma concentrations (Cmax) and dose-normalized by the subject weight Cmax (NCmax) were higher in females than in males. Furthermore, NCmax and dose-normalized by the subject weight AUC (NAUC0-24h, NAUC0-∞) ratios of simvastatin hydroxy acid to simvastatin lactone in females were higher than in males.
  
  
  CONCLUSIONS
  This study indicates that gender affects the plasma concentrations of active simvastatin hydroxy acid, but has no significant effect on parent simvastatin lactone. Raised plasma concentrations of simvastatin hydroxy acid in females may enhance the risk of systemic adverse effects during simvastatin lactone treatment.
authors.forename: Weihong
authors.initials: W
authors.lastname: Yang
authors.forename: Hongpong
authors.initials: H
authors.lastname: Xu
authors.forename: Yanliang
authors.initials: Y
authors.lastname: Song
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Xinwei
authors.initials: X
authors.lastname: Ren
authors.forename: Dengzhi
authors.initials: D
authors.lastname: Zhao
authors.forename: Yaoxin
authors.initials: Y
authors.lastname: Cai
authors.forename: Shengjun
authors.initials: S
authors.lastname: Zhang
authors.forename: Jianmin
authors.initials: J
authors.lastname: Huang
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Zhang
authors.forename: Tianyi
authors.initials: T
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Zuo
mesh_terms: D000328:Adult; D019540:Area Under Curve; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D007783:Lactones / Q000493:pharmacokinetics; D008297:Male; D012727:Sex Characteristics; D019821:Simvastatin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007783:Lactones; C532833:simvastatin hydroxyacid; D019821:Simvastatin