Kinetics of adriamycin injected proximal to a tumor: a comparative study between venous and arterial injections

A kinetic study of plasma concentration of Doxorubicin (Adriamycin) was performed in 25 cases of malignant melanoma of the extremity with malignant adenopathy, treated with the same dose (20 mg per m2). Drug concentration was measured using a radioimmunoassay, with good intra-assay and inter-assay reproducibility. The kinetic analysis used the multiple compartmental method and a simulation of the plasma curves. Adriamycin injected intravenously quickly leaves the plasma into an exchangeable compartment with a slow plasma return and subsequent prolonged mean duration of the plasma half life at a low concentration. Thus, the intravenous perfusion results in a high plasma concentration only during the time of infusion. After intra arterial injection proximal to the tumor, a fraction variable (average 35%) is not released back into the circulation, or released very slowly. This local sequestration (important in terms of local concentration) explains the efficiency and the potential local toxicity of this method of administration. The rapid release of about 70% of the drug into the plasma, with kinetics similar to that observed after intravenous infusion, allows for no significant reduction of systemic toxicity.