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

Antraquinone glycosides are an important class of antineoplastic drugs, fre quently used for treatment of a variety of malignancies in children. Doxoru bicin (Dox) is the most frequently used drug within this class of antineopl astics, 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 th e present study was to investigate the pharmacokinetics of Dox and Epi in c hildren with acute lymphocytic leukemia, in total 31 patients (13 females a nd 18 males; median age 5.4 years; range 0.73-15.3 years) were studied usin g a simplified sampling procedure. The pharmacokinetic differences of the t wo drugs were established by their simultaneous administration. The plasma pharmacokinetics of neither Dox nor Epi correlated with the age of the pati ents. There were no gender differences in dose-normalized maximum concentra tions of neither Dox nor of Epi. The inter-patient variation of the dose-no rmalized 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 phar macokinetic differences of cox and Epi in children, although less pronounce d than in adults, are still of a magnitude that might be of clinical import ance. [(C) 2000 Lippincott Williams & Wilkins.].