Pharmacokinetics and pharmacodynamics study of high dose epirubicin in cancer patients

Objective:This study was designed to characterize the pharmacokinetics and pharmacodynamics of high dose epirubicin in cancer patients Methods:Eleven cancer patients were administered a dose of 100 mg/m 2 epirubicin The concentration of epirubicin in the blood were determined by high performance liquid chromatographic (HPLC)assay The modelling data were performed with a compartment pharmacokinetic modelling program (PCNONLIN) Hematological toxicity was used as the pharmacodynamic index The relationships between the pharmacokinetics and pharmacodynamics and other factors affecting dose modulation were assessed Results: The pharmacokinetics of high dose epirubicin was best described by a typical three compartment model It showed wide interindividual variation There was no correlation between its pharmacokinetics and pharmacodynamics Age was negatively correlated with epirubicin clearance Conclusions: There was no difference for the pharmacokinetic parameters between high dose and low dose Total clearance appears to be decreased with age and indicating that it is necessiary to reduce dose for the elderly patients Tolerance of the patients receiving a dose of 100 mg/m 2 epirubicin was good