论文部分内容阅读
目的本试验以曲线下面积和峰值浓度为评价依据,采用有限采样法估算盐酸二甲双胍的生物等效性,为临床应用提供试验依据。方法试验以20名健康志愿者作为研究对象,口服盐酸二甲双胍参比制剂和受试制剂1 000 mg后采集若干时间点血浆样品,采用高效液相色谱法测定各采样时间点盐酸二甲双胍的血药浓度,用经典方法计算药动学参数,评价生物等效性。另以参比制剂血药浓度数据作为建模数据,采用有限采样法估算药动学参数ρmax、AUC0-24。外部验证以受试制剂数据进行,选择最佳模型进行生物等效性评价。内外部验证均采用Jackknife法。结果结果表明,以2个和3个血药浓度数据点预测的药动学参数回归模型的线性关系较好(r2>0.94),内部和外部验证表明,以血药浓度数据点ρ1,ρ1.5,ρ2,ρ4,ρ10同时估算ρmax、AUC0-24的准确性最好,各参数间比较差异无统计学意义(P<0.05),生物利用度(F)为(100.42±15.05)%。与经典法评价结果一致。结论用有限采样法估算口服盐酸二甲双胍制剂药动学参数是可行的,可以为生物等效性研究提供新的计算方法。
Objective To evaluate the bioequivalence of metformin hydrochloride by the finite sampling method under the area under the curve and the peak concentration for the purpose of providing experimental basis for clinical application. Methods Twenty healthy volunteers were enrolled in this study. After oral metformin hydrochloride reference formulation and 1000 mg of test preparation were taken orally, plasma samples at different time points were collected. The plasma concentrations of metformin hydrochloride at each sampling time were determined by HPLC. Pharmacokinetic parameters were calculated using classical methods to evaluate bioequivalence. Another reference drug plasma concentration data as modeling data, using finite sampling method to estimate pharmacokinetic parameters ρmax, AUC0-24. External validation was performed on the data of the test preparations and the best model was selected for bioequivalence assessment. Internal and external validation using Jackknife method. The results showed that the linear regression model of the pharmacokinetic parameters predicted by two and three plasma concentration data points had a good linear relationship (r2> 0.94), and the internal and external validation showed that the plasma concentration data points ρ1 and ρ1. 5, ρ2, ρ4, ρ10 and pmax at the same time. The accuracy of AUC0-24 was the best. There was no significant difference between the parameters (P <0.05) and the bioavailability (F) was (100.42 ± 15.05)%. Consistent with the results of the classic method. Conclusions It is feasible to use finite sampling method to estimate the pharmacokinetic parameters of oral metformin hydrochloride, which can provide a new calculation method for bioequivalence study.