Physiologically Based Kinetics Of Azt

Azt 的生理动力学

• 批准号: 6543017
• 负责人: Christopher J Portier
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6543017
• 关键词: clinical research; drug metabolism; human data; mathematical model; mathematics; model design /development; pharmacokinetics; zidovudine

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

建立了3 '-叠氮-3'-脱氧胸苷（AZT，齐多夫定）在人体内分布的生理药代动力学（PBPK）模型。编写微分方程来描述器官和组织中发生的吸收、分布、代谢和消除。模型中采用的生理生化参数均来自文献。根据AZT的正辛醇/水分配系数计算从血液到组织隔室的分配系数。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和PBPK模型预测的AZT浓度之间获得了密切的协议。这些结果证明了PBPK建模用于预测组织和器官浓度的合理性。该模型可用于制定个体化暴露方案，以根据个体的测量值获得特定组织中的特定浓度。这是说明了一个假设的药物方案的例子