科研之友
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摘要
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 (C-max) and dose-normalized by the subject weight C-max (NCmax) were higher in females than in males. Furthermore, NCmax and dose-normalized by the subject weight AUC (NAUC(0-24h), NAUC(0-infinity)) ratios of simvastatin hydroxy acid to simvastatin lactone in females were higher than in males. Conclusion: 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.
- 出版日期2014-2
- 单位郑州大学; 郑州铁路职业技术学院
