A review of population pharmacokinetic models of posaconazole

Aims: Posaconazole is often used for the prophylaxis and treatment of invasive fungal infections (IFI). However, intra- and inter-individual differences and drug interactions affect the efficacy and safety of posaconazole. Precision dosing of posaconazole based on the population pharmacokinetic (PopPK) model may assist in making significant clinical decisions. This review aimed to comprehensively summarize the published PopPK models of posaconazole and analyze covariates that significantly influence posaconazole exposure. Methods: Articles published until May 2022 for PopPK analysis of posaconazole were searched in PubMed and EMBASE databases. Demographic characteristics, model characteristics, and results of PopPK analysis were extracted from the selected articles. In addition, the steady-state pharmacokinetic profiles of posaconazole were simulated at different covariate levels and dosing regimens. Results： Out of the 13 studies included in our review, nine studies included adults, three included children, and one included both adults and children. All oral administration models were one-compartment models, and all intravenous administration models were two-compartment models. Body weight, proton pump inhibitors, and incidence of diarrhea were found to be important covariates. In addition, age, sex, total protein, rifampin, phenytoin, intake of nutritional supplements, levels of bilirubin and gamma-glutamyl transferase, and administration of chemotherapy also appeared as covariates in several PopPK models. Conclusion: Posaconazole exposure was found to be influenced by various factors such as the type of formulation, the incidence of diarrhea, body weight, and use of concomitant medications. It was concluded that routine therapeutic drug monitoring was required for dose adjustment and in promoting individualized dosing.