Population pharmacokinetics of doxorubicin: A systematic review

Because of the high interindividual pharmacokinetic variability, several population pharmacokinetic (PopPK) models of doxorubicin (DOX) were developed to characterize factors influencing such variability. However, significant predictors for DOX pharmacokinetics identified using PopPK models varied across studies. Thus, this review aims to summarize PopPK models of DOX and its metabolites (if any) as well as significant covariates influencing DOX (and its metabolites) pharmacokinetic variability. A systematic search from PubMed, CINAHL Complete, Science Direct, and SCOPUS databases identified 503 studies. Of these, 16 studies met the inclusion criteria and were included in this review. DOX pharmacokinetics was described with two- or three-compartment models. Most studies found a significant increase in DOX clearance with an increase in body surface area from the median value of 1.8 m² . Moreover, this review identified that while a 10-year increase in patient age resulted in a decrease in DOX clearance in adults and the elderly, younger children had lower DOX clearance compared to older children. Further, low DOX exposure was observed in pregnant women, and thus dosage adjustment is required. Concerning model applicability, predictive performance assessment of these published models should be performed before implementing such models in clinical practice.