Arterial drug infusion with extracorporeal removal. I. Theoretic basis with particular reference to the brain

The pharmacokinetic advantage of intra-arterial drug administration can be improved if blood from the infused region is perfused through a suitable extracorporeal device. The extent of improvement depends on the blood flow to the device, the fraction of the vascular drainage that can be obtained, and the drug extraction by the device. A relatively simple equation is derived to assess the pharmacokinetic advantage and to define the governing parameters. Application of the theory to the treatment of brain tumors includes a discussion of the selection of an experimental animal and interpretation of results. It is suggested that tumor exposure to carmustine comparable to that associated with very high tumor cell kill in vitro may be feasible with little or no systemic toxicity.