Physiologically Based Kinetics Of Azt

建立了3‘-叠氮-3’-脱氧胸苷(AZT，Zidovudine)在人体内的药代动力学模型。微分方程式被写成描述发生在器官和组织中的吸收、分布、代谢和消除。模型中使用的生理生化参数来自文献。根据AZT的正辛醇/水分配系数计算从血液到组织室的分配系数。该模型预测了血液和几个器官中的药物浓度。实验药代动力学数据与PBPK模型预测的AZT浓度之间有很好的一致性。这些结果证明了使用PBPK模型预测组织和器官浓度的基本原理。该模型可用于开发个性化的暴露方案，以根据个人的测量值获得特定组织中的特定浓度。这一点在一个假想的药物治疗方案中得到了说明。

A physiologically based pharmacokinetic (PBPK) model was constructed for 3'-azido-3'-deoxythymidine (AZT, Zidovudine) disposition in humans. Differential equations were written to describe absorption, distribution, metabolism and elimination occurring in organs and tissues. The physiological and biochemical parameters employed in the model were obtained from the literature. Partition coefficients from blood into tissue compartments were calculated based on the n-octanol/water partition coefficient of AZT. The model predicted drug concentrations in blood and several organs. Close agreement was obtained between experimental pharmacokinetic data and AZT concentrations predicted by the PBPK model. These results demonstrate the rationale use of PBPK modeling for the prediction of tissue and organ concentrations. The model can be used to develop individualized exposure regimens to obtain specific concentrations in specific tissues based upon measured values for the individual. This is illustrated in a hypothetical drug regimen example