Establishment of physiological based pharmacokinetic model of ritonavir and prediction of its drug-drug interactions
10.13699/j.cnki.1001-6821.2024.02.022
- VernacularTitle: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
- Author:
Ze-Xu SUN
1
;
Nan ZHAO
;
Ran XIE
;
Zhao-Qian LIU
Author Information
1. 中南大学湘雅药学院,湖南长沙 410013
- Keywords:
ritonavir;
physiologically based pharmacokinetic;
pharmacokinetics;
drug-drug interaction
- From:
The Chinese Journal of Clinical Pharmacology
2024;40(2):259-263
- CountryChina
- Language:Chinese
-
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.
