A pharmacokinetic study of adriamycin and 4'epi-adriamycin after simultaneous intra-arterial liver administration.

The plasma pharmacokinetics of adriamycin and 4'epi-adriamycin were studied in patients with malignant tumors of the liver after simultaneous regional administration of equal amounts of the two anthracyclines by the arterial route. The use of 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. On average the area under the plasma concentration time curve (AUC) and the maximum plasma concentration (Cmax) were 2.1 and 1.7 times larger for adriamycin than for 4'epi-adriamycin, respectively. 4'Epi-adriamycin was eliminated faster than adriamycin, the terminal half-life time being on the average 1.5 times higher for adriamycin. These findings are in agreement with what has previously been observed after intravenous administration. The plasma concentrations of the 13-hydroxy metabolites did not exceed 30 ng ml-1. The AUC values of these metabolites were on average 20% of the AUC values of the intact drugs.