Comparative pharmacokinetic study of adriamycin and 4'epi-adriamycin after their simultaneous intravenous...

The plasma pharmacokinetics of adriamycin and 4'epi-adriamycin have been studied in 6 patients with ovarian carcinoma after simultaneous intravenous administration of equal amounts of the two anthracyclines. A highly selective liquid chromatographic analytical method permitted quantification of plasma concentrations of the two drugs as well as their corresponding 13-hydroxy metabolites. The plasma concentrations of each drug followed a three-compartment open model, with great interindividual variation in the pharmacokinetic parameters. On average, the area under the plasma concentration time curve (AUC) and the maximum plasma concentration (Cmax) were 1.6- and 1.2-times larger for adriamycin than for 4'epi-adriamycin. 4'Epi-adriamycin was eliminated faster than adriamycin by 4 of the 6 patients, the average terminal half-life of the latter being 1.4-times longer. The plasma concentrations of the 13-hydroxy metabolites did not exceed 20 ng/ml. Their AUC values averaged 23% of those of the intact drugs.