An analytical model for intra-arterial versus intravenous infusion of Adriamycin

Intra-arterial infusion of Adriamycin (doxorubicin) has increasing clinical usage in various chemotherapeutic protocols for treatment of sarcomas and other tumors. This route of drug delivery is generally believed to provide better delivery of drug to the tumor than intravenous infusion. However, the differential delivery of drug to the tumor for the two methods has not been adequately described. An analytical model has been developed to investigate the hemodynamics of intra-arterial Adriamycin in terms of various parameters including location of injection; tumor site, resistance, and blood flow; relative resistances and blood flows in adjacent structures; and the pharmacokinetics of Adriamycin plasma concentration. A three-phase exponential model is fitted to experimental plasma concentration measurements and used in the formulation of equations describing tumor Adriamycin exposure. For typical values of tumor blood flow (4-20 ml/min/100 gr) and size (1,000 gm), it is estimated that with intravenous injection of Adriamycin the tumor is exposed to only 4-19% of the injected drug. Substantially higher doses of Adriamycin are delivered to the tumor by intra-arterial injection. Typically 3-4 times more drug flows through the tumor when injected into a major artery proximal to the tumor-feeding vessel, as into the common femoral artery for a sarcoma of the leg. With injection directly into a major tumor arterial feeding vessel, as much as 6 to 26 times the mass of drug is delivered to the tumor compared to a comparable intravenous injection.hus, smaller doses of drug should be required for tumorcidal activity and systemic toxicity of the drug may be reduced.(ABSTRACT TRUNCATED AT 250 WORDS)