生理药代动力学模型在预测转运体介导药物相互作用中的应用

Application of physiologically based pharmacokinetic models in the prediction of drug-drug interactions mediated by transporters

生理药代动力学模型通过与经典药代动力学模型类似的数学框架构建而成,并按已知的生理学知识设置参数,由大量分别对应于体内不同器官或组织的房室组成,并通过类似血液循环的系统而连接。因能较准确的预测药物在体内过程,故其在药物研发行业尤其是药物相互作用领域,逐渐崭露头角。本文将从生理药代动力学模型的概念、与经典模型的优势比较及其在转运体介导的药物相互作用中的应用等方面进行综述。

Physiologically based pharmacokinetic（PBPK） models are built using a mathematic framework which is similar to these classic pharmacokinetic（PK） models,and are parameterized based on known physiology knowledge,and comprise many compartments corresponding to different organs and tissues in the body,which are connected by flow rates that parallel the circulating blood system.The values of PBPK models are gradually appreciated in the industry of drug development,especially in the field of drug- drug interaction due to their robust ability to predict drugs＇ kinetic process in vivo.Then some basic concepts,advantages over classic models and their applications in drug- drug interaction fields associated with transporters of PBPK models are reviewed in the next context.