Abstract
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.