酰托普利在健康男、女受试者体内的药代动力学研究

Pharmacokinetic studies of ceptopril in healthy male and female volunteers

目的:研究新型血管紧张素转换酶抑制剂酰托普利在健康男、女受试者体内的药代动力学和安全性。方法:10名健康男、女受试者(男、女各半)连续口服酰托普利30mg(bid,7d),另有10名健康男、女受试者(男、女各半)分别在空腹和进食标准餐后单剂量口服酰托普利60mg,按规定时间点取血并测定血浆药物浓度,采用WinNonlin软件计算药代动力学参数。结果:受试者首次和末次口服30mg酰托普利后的平均Cmax分别为(279±100)、(299±101)μg/L,tmax分别为(1.2±0.5)、(1.2±0.3)h,t1/2分别为(1.3±0.9)、(1.3±0.5)h,AUC0-t分别为(421±107)、(461±152)μg.L-1.h,在二者之间无统计学差异。比较受试者单剂量空腹和餐后口服酰托普利60mg,tmax明显延后,Cmax有所降低,其他参数AUC、t1/2等在两种给药方式间无差异。各试验组中男、女受试者的药动学参数均无统计学差异。结论:本研究未观察到酰托普利有药物蓄积现象,进食影响该药的吸收速率,不影响其吸收程度,其体内过程不受性别差异的影响。

AIM： To study the pharmacokinetic profiles of ceptopril, a new ACE inhibitor, in Chinese healthy male and female volunteers. METHODS： 10 healthy volunteers （5 males and 5 females） were enrolled and 30 mg ceptopril oral dose was given twice daily for 7 days. Another 10 healthy volunteers （5 males and 5 females） were treated with 60 mg ceptopril in the fed and fasted conditions. With the analysis of HPLC for the concentrations of ceptopril in plasma, pharmacokinetic parameters were calculated by Win- Nonlin software. RESULTS： No significant difference was observed between the pharmacokinetic parameters of the 1st dose and the last dose （P 〉 0.05）, with values as follows： tmax（1.2±0.5） h and （1.2 ± 0.3） h, Cmax （279 ± 100） μg/L and （299 ± 101 ） μg/L, AUC0-1 （421 ± 107） μg·L^-1·h and （461 ± 152） μg·L^-1·h, t1/2（1.3 ±0.9） h and （1.3±-0.5） h.Compared with those in fasted condition, tmax was prolonged, and AUC and Cmax were not significantly changed in fed condition. There was no significant difference between the male and female volunteers. CONCLUSION： There was no accumulation when ceptopril was given with multiple doses. Food affected the absorption rate of ceptopril, but did not decrease its exposure. No sex difference was observed.