Abstract: Objective: This study was designed to characterize the pharmacokinetics and pharmacodynamics of high dose epirubicin in cancer patients. Methods: Eleven patients with malignant tumors were administered with a dose of 100 mg.m^-2 epirubicin. The concentration of epirubicin was 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 among 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 closely correlated with epirubicin clearance. Conclusions: There was no difference in the pharmacokinetic parameters between high dose and low dose. Total clearance appeared to decrease with age, which indicates the necessity of reducing dose for the elderly patients. The tolerance was good for patients receiving a dose of 100 mg.m^-2 epirubicin.

Key words: High dose epirubicin, Pharmacokinetics, High dose epirubicin, Pharmacokinetics, Pharmacodynamics, Pharmacodynamics