Becquemont L, Neuvonen M, Verstuyft C, Jaillon P, Letierce A, Neuvonen P J, Funck-Brentano C
Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Service de Génétique Moléculaire et Pharmacogénétique, and Départment de Pharmacologie, Université Paris-Sud (XI), Le Kremlin Bicetre, France.
Clin Pharmacol Ther. 2007 May;81(5):679-84. doi: 10.1038/sj.clpt.6100098. Epub 2007 Feb 14.
The aim of this study was to determine the influence of amiodarone on the pharmacokinetics of simvastatin and pravastatin in humans. This was a prospective, crossover, randomized, open-label study performed in 12 healthy volunteers comparing the pharmacokinetics of a single oral dose of simvastatin (40 mg) or pravastatin (40 mg) taken alone and after 3 days of amiodarone (400 mg/day). Amiodarone increased simvastatin acid AUC (area under the plasma concentration-time curve)0-24 h, peak plasma concentration (Cmax), and t1/2 by 73% (P=0.02), 100% (P=0.02), and 48% (P=0.06), respectively, whereas it did not significantly alter pravastatin pharmacokinetics. Point estimates and 90% confidence intervals for simvastatin acid, simvastatin lactone, and pravastatin AUC0-24 h were 154% (109-216%), 155% (109-227%), and 86% (63-118%), respectively. If amiodarone and a statin have to be simultaneously prescribed, pravastatin should be preferred to simvastatin in order to avoid a drug interaction.
本研究的目的是确定胺碘酮对辛伐他汀和普伐他汀在人体内药代动力学的影响。这是一项前瞻性、交叉、随机、开放标签研究，在12名健康志愿者中进行，比较单独服用单剂量口服辛伐他汀（40毫克）或普伐他汀（40毫克）以及在服用胺碘酮（400毫克/天）3天后的药代动力学。胺碘酮使辛伐他汀酸0至24小时的血浆浓度-时间曲线下面积（AUC）、血浆峰浓度（Cmax）和半衰期（t1/2）分别增加了73%（P = 0.02）、100%（P = 0.02）和48%（P = 0.06），而对普伐他汀的药代动力学没有显著影响。辛伐他汀酸、辛伐他汀内酯和普伐他汀0至24小时AUC的点估计值和90%置信区间分别为154%（109 - 216%）、155%（109 - 227%）和86%（63 - 118%）。如果必须同时开具胺碘酮和他汀类药物，为避免药物相互作用，应优先选择普伐他汀而非辛伐他汀。
