中国临床药理学杂志2024，Vol.40Issue(2)：259-263,5.DOI:10.13699/j.cnki.1001-6821.2024.02.022
利托那韦生理药代动力学模型的建立及其介导的药物相互作用预测
Establishment of physiological based pharmacokinetic model of ritonavir and prediction of its drug-drug interactions
摘要
Abstract
Objective To develop a physiological pharmacokinetic(PBPK)model of ritonavir,simulate ritonavir-mediated drug interactions,and provide future predictions for ritonavir pharmacokinetics(PK)and drug-drug interaction(DDI).Methods The PBPK model of ritonavir was constructed by searching relevant databases,collecting data on the physicochemical properties,PK,DDI related parameters and clinical studies of ritonavir,and using PK-Sim software to optimize and validate the parameters of the model to evaluate the performance of the constructed PBPK model in describing the PK characteristics and predicting the DDI of ritonavir.Results The ritonavir PBPK model demonstrated good performance,and by calculating the geometric mean folded error(GMFE)between the Sim and actual Obs values,the GMFEs of ritonavir AUC and Cmax were 1.11 and 1.16,respectively,and the GMFEs of ritonavir AUC and Cmax after combination with ritonavir were 1.24 and 1.26,respectively.Conclusion The PBPK model of ritonavir has been successfully constructed,and the effect of ritonavir on the metabolic enzyme cytochrome P450 3A4 is significant.Therefore,when ritonavir is combined with the victim drugs,individualized dosing can be guided according to the PBPK model.关键词
利托那韦/生理药代动力学模型/药代动力学/药物相互作用Key words
ritonavir/physiologically based pharmacokinetic/pharmacokinetics/drug-drug interaction分类
医药卫生引用本文复制引用
孙泽旭,赵楠,解染,刘昭前..利托那韦生理药代动力学模型的建立及其介导的药物相互作用预测[J].中国临床药理学杂志,2024,40(2):259-263,5.基金项目
国家自然科学基金资助项目(82173901) （82173901）
湖南省科技人才托举工程基金资助项目(2023TJ-G03) （2023TJ-G03）
