生理药代动力学模型在肝功能不全人群中的建立与应用

Establishment and application of physiologically based pharmacokinetic model in patients with hepatic impairment

生理药代动力学模型(physiologically based pharmacokinetic model,PB-PK model)是利用数学模型对血流在全身器官的循环情况进行模拟,定量描述药物在机体内的行为特征的手段。将PB-PK模型应用于特殊人群,预测药物在特殊人群中的药动学行为,能够为临床合理用药提供支持。近年来,慢性肝脏疾病(chronic liver diseases,CLDs)逐渐成为困扰人们的重要健康问题,由于患者肝功能受损,药物在体内的处置过程将发生一定改变。因此,需要评估肝功能不全对药物体内吸收、分布、代谢及排泄(absorption,distribution,metabolism,elimination,ADME)的影响,以保证患者用药的安全性及有效性。基于这一情况,PB-PK模型可以根据肝功能水平,精准预测药物在患者体内的ADME过程,在指导临床合理用药中发挥重要作用。本综述将从肝脏功能对药物ADME过程的影响出发,总结讨论PB-PK模型如何根据肝功能不全患者生理、病理变化搭建模型,并进行较为准确的外推预测。

Physiologically based pharmacokinetic(PB-PK)model simulates the circulation of blood flow in systemic organs by using mathematical model to quantitatively describe the behavior characteristics of drugs in the body.The application of PB-PK model to special population to predict the pharmacokinetic behavior of drugs in special populations can provide support for clinical rational drug use.In recent years,chronic liver disease has gradually become an important health problem.Due to the impairment of patients'liver function,the disposal process of drug in vivo will change to some extent.Therefore,it is necessary to evaluate the impact of liver dysfunction on the drug absorption,distribution,metabolism,elimination(ADME)in order to ensure the safety and effectiveness of drug use.PB-PK model can accurately determine the ADME process of drugs in patients according to the level of liver function,and play an important role in guiding clinical rational drug use.This review will start from the impact of liver function on the process of drug ADME,summarize and discuss how PB-PK model can build a model according to the physiological and pathological changes of patients with liver dysfunction for more accurate extrapolation prediction.