多潘立酮片人体生物等效性研究

Bioequivalence study of domperidone tablets in healthy Chinese volunteers

目的用高效液相色谱-质谱联用法(LC-MS/MS)测定受试者口服多潘立酮制剂后的血药浓度,估算受试制剂和参比制剂的药代动力学参数,评价2种制剂的生物等效性和相对生物利用度。方法采用随机二交叉设计试验,24例男性健康志愿受试者,单剂量口服受试制剂和参比制剂多潘立酮片。以LC-MS/MS测定血浆中多潘立酮的浓度。采用BAPP3.0软件处理计算主要药动学参数。结果受试制剂和参比制剂血浆中多潘立酮的半衰期(t1/2)分别为(10.2±1.9)和(10.2±2.2)h;达峰浓度(Cmax)分别为(26±11)和(25±12)μg/L,达峰时间(tmax)分别为(0.7±0.5)和(0.6±0.3)h;药-时曲线下面积(AUC0～36h)分别为(75±24)和(70±27)μg·h-1·L-1;AUC0-∞分别为(80±26)和(74±28)μg·h-1·L-1;人体相对生物利用度为(114±30)%。结论 2种制剂在健康人体内具有生物等效性。

Objective To evaluate the relative bioequivalence of two domperidone preparations in healthy Chinese volunteers by estimated pharmacokinetics based on plasma concentrations of the drugs detected by LC-MS/MS.Methods A single oral dose of two preparations was given to 24 healthy male volunteers according to a randomized crossover design.Plasma drug concentrations were determined by LC-MS/MS.The pharmacokinetic parameters were calculated by BAPP3.0.Results The major pharmacokinetic parameters of domperidone in test and reference preparations were as follows：t1/2（10.2±1.9）and（10.2±2.2）h,Cmax（26±11）and（25±12）μg/L,tmax（0.7±0.5）and （0.6±0.3）h,AUC0～36h（75±24）and（70±27）μg·h-1·L-1,AUC0-∞（80±26）and（74±28）μg·h-1·L-1,respectively.The relative bioavailability of test preparation was （114±30）%.Conclusion The two preparations were bioequivalent in human body.