Yano Y, Oguma T, Nagata H, Sasaki S
Developmental Research Laboratories, and Discovery Research Laboratories II, Shionogi & Co., Ltd., Osaka, Japan.
J Pharm Sci. 1998 Oct;87(10):1177-83. doi: 10.1021/js9801337.
A new pharmacodynamic model for the analysis of in vitro bactericidal kinetics was developed based on the logistic growth model, with the bacterial phases divided into two compartments. The model equations are expressed as nonlinear simultaneous differential equations, and the Runge-Kutta-Gill method was adopted to numerically solve the equations in both the simulation and the least squares curve-fitting procedures. The model can describe the initial killing and the regrowth phases and can explain the nonlinear dependence of the killing rate on the drug concentration. The model can also explain the plateau in the bacterial growth curve that is often observed in in vitro experiments. The model was applied to analysis of the in vitro time-killing data of beta-lactam antibiotics, S-4661, meropenem, imipenem, cefpirome, and ceftazidim against three types of bacteria, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The results of curve-fitting using the least squares program MULTI (Runge) showed good fits for all types of drugs and bacteria. The relationship between the characteristics of the drug-bacteria interactions and the estimated pharmacodynamic parameters is discussed.
基于逻辑斯谛生长模型开发了一种用于分析体外杀菌动力学的新药效学模型，细菌阶段分为两个隔室。模型方程表示为非线性联立微分方程，在模拟和最小二乘曲线拟合过程中均采用龙格 - 库塔 - 吉尔方法对方程进行数值求解。该模型可以描述初始杀菌阶段和再生长阶段，并能解释杀菌速率对药物浓度的非线性依赖性。该模型还可以解释体外实验中经常观察到的细菌生长曲线中的平台期。将该模型应用于分析β - 内酰胺类抗生素S - 4661、美罗培南、亚胺培南、头孢匹罗和头孢他啶对三种细菌（大肠杆菌、铜绿假单胞菌和金黄色葡萄球菌）的体外杀菌时间数据。使用最小二乘法程序MULTI（Runge）进行曲线拟合的结果表明，对所有类型的药物和细菌都有良好的拟合效果。讨论了药物 - 细菌相互作用特征与估计的药效学参数之间的关系。
