缬沙坦片在中国健康受试者体内的生物等效性研究

Bioequivalence of Valsartan Tablets in healthy Chinese subjects

目的在健康受试者中空腹及餐后情况下评价缬沙坦片的吸收速度和吸收程度,评价受试制剂和参比制剂是否具有生物等效性。方法采用开放、单剂量、随机、3周期、部分重复交叉设计的生物等效性研究。每周期口服受试制剂或参比制剂40 mg。应用液相色谱-串联质谱(LC-MS/MS)方法测定血浆中缬沙坦浓度,使用Win Nonlin?6.4软件,计算药动学参数,评价两种制剂的生物等效性。结果空腹组受试制剂与参比制剂药时曲线下面积(AUC_(0~t))和AUC_(0~∞)的几何均数比值分别为100.39%和100.35%,90%置信区间(90%CI)分别为91.91%~109.67%和92.11~109.32%,完全落入80.00%~125.00%内。达峰浓度(C_(max))几何均值比值为97.61%,落在80.00%~125.00%内。餐后组受试制剂与参比制剂C_(max)、AUC_(0~t)和AUC_(0~∞)的几何均数比值分别为107.85%、105.03%和105.06%,90%CI分别为97.81%~118.92%、99.27%~111.12%和99.42%~111.02%,完全落入80.00%~125.00%内。结论缬沙坦片受试制剂和参比制剂在空腹和餐后状态下均具有生物等效性。

Objective The rate and degree of absorption of Valsartan Tablets and DIOVAN were evaluated on fasting and postprandial conditions in healthy male and female subjects to evaluate the bioequivalence between the two preparations.Methods An open,single-dose,randomized,three-cycle,partially replicated crossover design was used to study bioequivalence.Oral administration of test preparation or reference preparation 40 mg percycle.Oral administration of test preparation or reference preparation 40 mg per cycle.Plasma concentration of valsartan was determined by liquid chromatographer-tandem mass spectrometry(LC-MS/MS).Pharmacokinetic parameters were calculated by WinNonlin®6.4 software to evaluate the bioequivalence of the two preparations.Results The main pharmacokinetic parameters of fasting group were as follows:The geometric mean ratios of AUC_(0-t)and AUC_(0-∞)between test preparation or reference preparation were 100.39%and 100.35%,respectively.The 90%confidence intervals were 91.91%—109.67%and 92.11—109.32%,respectively.It's totally in the 80.00%—125.00%range.The point estimate of the geometric mean ratio of Cmax is 97.61%,which falls in the range of 80.00%—125.00%.The main pharmacokinetic parameters of the postprandial group are as follows:The geometric mean ratios of Cmax,AUC_(0-t)and AUC_(0-∞)between test preparation or reference preparation were 107.85%,105.03%and 105.06%,respectively.The 90%confidence intervals are 97.81%—118.92%,99.27%—111.12%and 99.42%—111.02%,respectively,which completely fall into the range of 80.00%—125.00%.Conclusion The test preparation of Valsartan Tablets were bioequivalent to reference preparation in fasting and postprandial states.