控释和缓释地尔硫卓胶囊在健康人体的生物等效性

Bioequivalence of diltiazem in control and sustained release capsules in healthy volunteers

目的研究地尔硫卓缓释和控释制剂(降压药)在健康人体的生物等效性。方法采用随机交叉给药方法,18名健康受试者单次和多次口服缓释或控释地尔硫卓胶囊。用高效液相色谱-紫外检测法测定血浆中的地尔硫卓浓度,用Winnolin软件计算药代动力学参数。结果控释和缓释地尔硫卓胶囊主要药代动力学参数,单次:tmax分别为(14.1±3.9)和(8.4±4.1)h,Cmax分别为(73±37)和(94±44)ng·mL-1,AUC0-36分别为(1348±590)和(1571±679)ng·h·mL-1,t1/2分别为(7.9±2.9)和(8.0±3.5)h。多次:tmax分别为(8.1±5.0)和(4.83±2.73)h,Cmax分别为(145±41)和(170±58)ng·mL-1,AUCss分别为(2232±642)和(2419±658)ng·h·mL-1,波动度DF分别为(103±32)%和(123±32)%。结论多次给药后,控释和缓释地尔硫卓具有生物等效性。

Objective To evaluate the bioequivalence of diltiazem control capsule and slow release capsule in Chinese healthy volunteers Methods A single oral dose (180 mg) of two diltiazem capsule was given to 18 healthy in a randomized cross-over study. The concentration of diltiazemin plasma were determined by HPLC-UV method developed in our laboratory.Results The main pharmacokinetic parameters of diltiazem in two formulations, control and sustained release capsules, were as follow:single dose :tmax were(14.1±3.9)h and(8.4±4.1)h,Cmax were(73±37) and(94±44)ng·mL-1, AUC0-36 were(1348±590)and (1571±679)ng·h·mL-1,t1/2 were(7.9±2.9)and(8.0±3.5) h ;multi-dose: tmax were(8.1±5.0)h and和(4.8±2.7)h,Cmax were(145±41)and(170±58)ng·mL-1, AUCss were(2232±642)and(2419±658)ng·h·mL-1,DF were (103±32)% and(123±32)%.Conclusion The two praperations are bioequivalence after multidose.