Intrahepatic and intravenous administration of adriamycin--a comparative pharmacokinetic study in patients with malignant liver tumours

Abstract

The pharmacokinetics of adriamycin in patients with malignant tumours of the liver were studied after peripheral intravenous treatment and after regional administration of the drug either by the arterial route or by the portal vein, with or without hepatic artery ligation. The plasma concentration of adriamycin after intravenous as well as after intrahepatic administration followed a three-compartment open model. The results in the present study confirm previous reports of a large inter-individual variation of the pharmacokinetics of adriamycin. After intravenous administration the individual variations in AUC/mg/m2 and Cp,max/mg/m2 (dose normalized area under plasma concentration time curve and dose normalized maximum plasma concentration, respectively) were more than 5-fold. The area under the plasma concentration time curve (AUC) was on the average 1.5 times higher after the peripheral intravenous administration than after intrahepatic administration. The reduction of maximum plasma concentration (Cp,max) of adriamycin after intrahepatic administration was even more pronounced than the reduction in AUC (mean value Cp,max iv/Cp,max ihep = 1.7). The plasma concentration of adriamycinol did not exceed 20 ng/ml. The AUC values of adriamycinol were 20% (median value) of the AUC values of adriamycin, indicating the importance of adriamycinol in the adriamycin therapy.