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本研究以药动学参数为指标,评价有限采样法估算二甲双胍药动学参数的可行性,为二甲双胍的生物等效性评价及临床监测提供实验依据。以20名健康志愿者为研究对象,口服盐酸二甲双胍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二甲双胍的血药浓度,以LSS建立回归数学模型,用Jacknife法验证回归模型的准确性。结果表明,单个血药浓度-时间点预测药动学参数,回归模型,线性关系较差;部分2点和3点预测药动学参数,回归模型,线性关系较好(r2>0.9,P<0.05),其中以C2,C6预测AUC0?24 h和C1.5,C2预测Cmax的回归模型和线性关系最佳,且准确性好。因此,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。
In this study, pharmacokinetic parameters as an index to evaluate the feasibility of finite sampling method to estimate pharmacokinetic parameters of metformin, to provide experimental evidence for the evaluation of bioequivalence and clinical monitoring of metformin. A total of 20 healthy volunteers were enrolled in this study. Plasma samples of metformin hydrochloride 1 000 mg were collected after oral administration of metformin hydrochloride at different time points. Plasma concentrations of metformin at various time points were measured by HPLC. Regression mathematical models were established by LSS. The accuracy of the law validation regression model. The results showed that the prediction of pharmacokinetic parameters and regression models at a single plasma concentration-time point showed a poor linearity. The prediction of pharmacokinetic parameters and regression models at 2 and 3 points showed good linearity (r2> 0.9, P < 0.05). Among them, the regression model predicting Cmax with C2 and C6 predicted AUC0? 24 h and C1.5, C2 had the best linear relationship with good accuracy. Therefore, it is feasible to use the limited sampling method to estimate the pharmacokinetic parameters of oral metformin hydrochloride.