A comparative pharmacokinetic study of doxorubicin and 4′-epi-doxorubicin in children with acute lymphocytic leukemia using a limited sampling procedure

Antraquinone glycosides are an important class of antineoplastic drugs, frequently used for treatment of a variety of malignancies in children. Doxorubicin (Dox) is the most frequently used drug within this class of antineoplastics, 4'-epi-doxorubicin (Epi), a Dox isomer, was developed with the aim of reducing risks for fatal heart toxicity observed with Dox. The aim of the present study was to investigate the pharmacokinetics of Dox and Epi in children with acute lymphocytic leukemia, in total 31 patients (13 females and 18 males; median age 5.4 years; range 0.73-15.3 years) were studied using a simplified sampling procedure. The pharmacokinetic differences of the two drugs were established by their simultaneous administration. The plasma pharmacokinetics of neither Dox nor Epi correlated with the age of the patients. There were no gender differences in dose-normalized maximum concentrations of neither Dox nor of Epi. The inter-patient variation of the dose-normalized maximum concentrations of Dox and Epi is larger among females than among males. The C-max ratio Dox/Epi was 1.39+/-0.19 (mean+/-SD). The pharmacokinetic differences of cox and Epi in children, although less pronounced than in adults, are still of a magnitude that might be of clinical importance. [(C) 2000 Lippincott Williams & Wilkins.].