阿折地平片的人体药动学研究

Study on Pharmacokinetics of Azelnidipine Tablet in Healthy Volunteers

目的:考察阿折地平片在人体内的药动学特性。方法:采用液-质联用(LC-MS)法,测定24名健康受试者口服受试制剂(单剂量含阿折地平8、16mg和多剂量)后血浆中阿折地平浓度。结果:单剂量口服阿折地平片8、16mg后,阿折地平的t1/2分别为(20.338±7.601)、(27.995±7.724)h,tmax分别为(3.333±1.303)、(3.667±0.985)h,cmax分别为(5.908±2.827)、(10.61±3.929)μg·L-1,AUC0～96h分别为(61.167±33.777)、(139.502±72.898)μg·h·L-1,AUC0～∞分别为(63.363±35.314)、(147.395±78.21)μg·h·L-1;多剂量口服阿折地平片8mg后,阿折地平的t1/2为(28.168±7.926)h,tmax为(3.167±0.718)h,cmax为(5.882±1.895)μg·L-1,AUC0～96h为(86.723±41.588)μg·h·L-1,AUC0～∞为(93.948±50.957)μg·h·L-1。结论:阿折地平片在8～16mg剂量范围内呈线性动力学特征,不同性别间药动学参数总体上差异不大,多剂量给药与单剂量给药的药动学参数基本一致。

OBJECTIVE： To study the pharmacokinetic characteristics of Azelnidipine tablet in healthy volunteers. METHODS： The concentration of azelnidipine in plasma was determined by LC-MS after 24 healthy volunteers received test preparation orally （single dose of azelnidipine 8, 16 mg and multi-dose）. RESULTS： The pharmacokinetic parameters after the single oral dose of Azelnidipine tablet 8 mg vs. 16 mg were as follows： tmax（20.338 ± 7.601） vs. （27.995 ± 7.724）h; tmax（3.333 ± 1.303） vs. （3.667 ± 0.985）h; Cmax（5.908± 2.827） vs. （10.61 ± 3.929）μg.L-1; AUC0-96h（61.167 ± 33.777） vs. （139.502± 72.898）μg.h.L-1; AUC0-∞（63.363± 35.314） vs. （147.395 ± 78.21）μg.h. L-1 The pharmacokinetic parameters after multi-dose of Azelnidipine tablet 8 mg were as follow： t,n（28.168 ＋ 7.926）h; tmax（3.167 ±0.718）h;Cmax（5.882 ± 1.895）μg.L-1;AUC0-96 h（86.723 ± 41.588）μg.h.L-1;AUC0-∞ （93.948 ± 50.957）μg. h. L-1. CONCLUSION： A linear pharmacokinetic profile of Azelnidipine tablet has been proved in the range of 8~16 mg. There is no significant difference in pharmacokinetic parameters between single dose and multi-dose and no signifi- cant difference between genders.