Pharmacokinetic models are developed for the distribution and disposition of drugs, environmental contaminants, and endogenous metabolites in animals and man. They provide a plausible set of equations that can be used to extrapolate data from animals to man and thereby improve chemotherapy and risk assessment. Emphasis has been placed on regional drug administration, and this had led to the development of spatially distributed models of drug transport in tissue. These analyses have provided considerable insight into the penetration depths of drugs administered intraperitoneally or by infusion into the brain. The penetration of cis-dichlorodiammineplatinum (II) (DDP) into peritoneal and subperitoneal tissue is being examined experimentally with an electron probe and the results compared with a reaction-diffusion equation of the process. A lumped model of DDP pharmacokinetics has been developed to include both metabolism to a mobile species and covalent binding to macromolecules. Pharmacokinetic theory which was developed for intra-arterial drug administration combined with extracorporeal treatment of venous drainage had been validated in the clinic. Systemic exposure to DDP has been reduced by 49-74% by hemodialysis of jugular venous drainage during intracarotid artery infusion for the treatment of malignant glioma. Preliminary results have shown the feasibility of documenting appropriate vascular drainage with indocyanine green.
