依那普利滴丸和片剂在人体内的药动学与生物等效性

Pharmacokinetics and bioequivalence of enalapril dripping pill and its tablet in Chinese healthy volunteers

目的评价依那普利滴丸与片剂2种制剂的生物等效性。方法20名健康男性受试者自身交叉单剂量口服依那普利滴丸和普通片20 mg,以HPLC-MS/MS法测定血浆中依那普利的代谢产物依那普利拉的浓度。采用DAS 2.0软件处理计算主要药动学参数,以方差分析与双向单侧t检验进行统计学分析。结果2种制剂血浆中依那普利拉的t_(1/2)分别为(7±s4)和(7±3)h,c_(max)分别为(61±19)和(64±27)μg·L^(-1),t_(max)分别为(4.1±0.8)和(3.9±0.7)h,AUC_(0～48)分别为(498±139)和(496±228)μg·h·L^(-1),AUC_(0～∞)分别为(515±145)和(520±241)μg·h·L^(-1),以依那普利拉计算的人体相对生物利用度为(114±38)%。结论2种制剂在健康人体内具有生物等效性。

AIM To evaluate the bioequivalence of enalapril dripping pill and its tablet in healthy volun- teers through HPLC-MS/MS measuring the blood concentration after orally taken enalapril preparation and estimating the pharmaeokinetics of enalapril driping pill and its tablets. METHODS A single oral dose of 20 mg enalapril was given to 20 healthy male volunteers according to a randomized crossover design. Plasma concentrations of enalaprilat, the metabolite of enalapril, were detected by HPLC-MS/MS. The pharmacokinetic parameters were calculated with the aid of DAS2.0 software. The bioequivalenee was calculated by analysis of variance and two one side t-test. RESULTS The pharmacokinetic parameters of enalaprilat of two preparations were as follows： t1/2 （7±s4） and （7±3） h; cmax （61± 19） and （64±27） μg.L-1; tmax. （4.1±0.8） and （3.9 ± 0.7） h; AUC0-48 （498 ± 139） and （496 _± 228） μg·h·L-1; AUC0-36 （515 ± 145） and （520 ± 241）μg.L-1, respectively. The relative bioavailability of enalaprilat was （114 ± 38） %. CONCLUSION The two formulations of enalapril were bioequivalent in human body.