Abstract
Aim: 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.
Keywords: posaconazole, population pharmacokinetics, nonlinear
mixed effects modeling, therapeutic drug monitoring