Khorasheh F, Sattari S, Gerayeli A, Ahmadi A M
Department of Chemical Engineering, Sharif University of Technology, Tehran, Iran.
J Pharm Pharm Sci. 1999 Sep-Dec;2(3):92-8.
For simple pharmacokinetic compartmental models, analytical solution to the governing differential equations along with common graphical methods provide a mean to evaluate the associated rate constants. These graphical methods, however, can not be used for the more complex multi-compartment models. Furthermore, parameter estimation using slope and intercept values from the graphical methods is often accompanied with error. In this study a numerical solution is applied for the solution of the governing differential equations and a simple direct search optimization procedure utilizing random numbers is used for pharmacokinetic parameter estimation.
The methodology is demonstrated with reference to experimental literature data for ciprofloxacin and ofloxacin whose pharmacokinetic behavior has been reported in terms of a two-compartment model.
Examination of the predicted drug concentrations from the graphical method and the optimization methodology indicate that both methods have comparable accuracy in predicting the drug concentrations. The graphical method, however, only shows good accuracy in the early stages both after i.v. and oral drug administration whereas the optimization procedure, due to the nature of the objective function formulation, provides good accuracy over the entire range of times after drug administration.
The methodology is simple, provides optimized parameters which accurately predict drug concentrations, and is flexible to include more weight on the early-time data or be extended to multi-compartment models.
对于简单的药代动力学房室模型，控制微分方程的解析解以及常见的图形方法提供了一种评估相关速率常数的手段。然而，这些图形方法不能用于更复杂的多室模型。此外，使用图形方法的斜率和截距值进行参数估计常常伴随着误差。在本研究中，采用数值解来求解控制微分方程，并使用一种利用随机数的简单直接搜索优化程序进行药代动力学参数估计。
参照环丙沙星和氧氟沙星的实验文献数据演示该方法，其药代动力学行为已用二室模型进行了报道。
对图形方法和优化方法预测的药物浓度进行检查表明，两种方法在预测药物浓度方面具有相当的准确性。然而，图形方法仅在静脉注射和口服给药后的早期阶段显示出良好的准确性，而优化程序由于目标函数公式的性质，在给药后的整个时间段内都具有良好的准确性。
该方法简单，能提供准确预测药物浓度的优化参数，并且灵活，可对早期数据赋予更大权重或扩展到多室模型。
