【作者】 尹雪芬； 杨劲；

【Author】 YIN Xue-fen,YANG Jin Key Laboratory of Drug Metabolism and Pharmacokinetics,Key Unit of SATCM for Pharmacokinetic Methodology of TCM Complex Prescription,China Pharmaceutical University,Nanjing 210009,Jiangsu,China

【机构】 中国药科大学药物代谢动力学重点实验室；

【摘要】 建立口服一房室Ka≈Ke的数学模型,解决药动学规律符合一房室模型的单剂量口服药物,其血药浓度-时间数据在应用计算机进行曲线拟合时,常因吸收速率和消除速率常数相近而使拟合发散、无法得到正确拟合结果这一问题。同时建立模型优劣判别标准。根据1968年Dost建立的口服一房室Ka≈Ke的数学模型能有效解决这一问题。列举盐酸二甲双胍血药浓度-时间数据,应用BAPP软件中经典口服一房室模型和口服一房室ka≈k的模型分别进行拟合,比较拟合结果。应用蒙托卡罗法模拟生成虚拟数据,进一步比较模型的稳健性和初值依赖性。对于具有一房室Ka≈ke药动学规律的口服药物使用口服一房室Ka≈k的模型进行拟合较好。利用模型的稳健性、初值依赖性两个指标可以有效地对药动学模型的优劣进行评判,进而建立模型优劣判别标准。更多还原

【Abstract】 In fitting the one-compartment open model to empirical data,it has frequently been found for single-dose administration that the absorption and elimination rate constants approach each other.If these rate constants tend to be equal,such combinations are impossible to solve with the general model equation.In 1968,Dost(t) published a special model function by which the problems associated with the general model function can be circumvented.We take metformin hydrochloride as an example,fitting concentrationtime profile data by the one-compartment model in which the absorption and elimination rate constants are equal and the classic one-compartment model respectively;Meanwill,rubustness and initial value dependence were evaluated.It should be indicated that both models come from the software of BAPP.RESULT:The one-compartment model with equal rate constant of absorption and elimination is more accuracy than an classic model.更多还原