Establishment of physiological based pharmacokinetic model of ritonavir and prediction of its drug-drug interactions
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.
ritonavirphysiologically based pharmacokineticpharmacokineticsdrug-drug interaction
国家科技期刊平台
NSTL
万方数据
维普
