Murata K, Kohno K
Products Formulation Research Laboratory, Tanabe Seiyaku Co., Ltd, Osaka, Japan.
Biopharm Drug Dispos. 1989 Jan-Feb;10(1):25-34. doi: 10.1002/bdd.2510100104.
Computer curve fittings were carried out to observed data as well as theoretically generated plasma concentrations of several drugs, using differential equations which contained nonlinear Michaelis-Menten type rate constants to discuss problems of initial parameter estimation in pharmacokinetic analysis. Calculation based on two different algorithms, each carried out by using SIMP (simplex method) and NONLIN (modified Gauss-Newton method) produced similar results. However, occasional divergence or unreasonable solutions occurred in a later case, when assumed values of Km and Vmax were used as initial parameters. A combined use of SIMP and NONLIN in which calculated values by SIMP were used as initial values for NONLIN, was shown to be effective to analyse plasma concentration data of indocyanine green bearing difficulty in estimating initial values. It is suggested that the successive method is useful for the curve fitting of plasma concentration with nonlinear pharmacokinetic rate processes.
利用包含非线性米氏型速率常数的微分方程，对几种药物的观测数据以及理论生成的血浆浓度进行计算机曲线拟合，以探讨药代动力学分析中初始参数估计的问题。基于两种不同算法的计算，每种算法均通过单纯形法（SIMP）和改进的高斯 - 牛顿法（NONLIN）进行，得出了相似的结果。然而，在后一种情况下，当将Km和Vmax的假设值用作初始参数时，偶尔会出现发散或不合理的解。结果表明，将SIMP和NONLIN结合使用（其中将SIMP的计算值用作NONLIN的初始值），对于分析在估计初始值方面存在困难的吲哚菁绿血浆浓度数据是有效的。建议这种连续方法对于具有非线性药代动力学速率过程的血浆浓度曲线拟合是有用的。
