Pharmacokinetics of Doxorubicin in cancer chemotherapy

Abstract

The pharmacokinetics (PK) of doxorubicin (DOX) is characterized by a large degree of inter-individual variation, which translates to unpredictability in the drug toxicity and response profiles from one individual to the next. In this work, we introduce a saturable model of DOX PK with fractal exponents using a population PK approach. The initial one-compartment model was expanded to a two-molecule model of DOX and encapsulated DOX, and a four-molecule, three-compartment model of DOX and its toxic metabolite doxorubicinol (DOL). Using this approach, the kinetic parameters of the molecules were developed by minimizing the weighted percentage variance of individual models. Our model provides interesting insights when testing the effects of some covariates on the PK of the molecules. We notice that factors such as patients' gender, race, body weight and liver impairment influence the elimination PK of DOX and DOL.