Pharmacokinetic models are developed for the distribution and disposition of drugs, environmental contaminants, and endogenous metabolites in animals and humans. They provide a plausible set of equations that can be used to extrapolate data from animals to humans and thereby improve chemotherapy and risk assessment. Consideration of regional drug delivery includes intra-arterial infusion, intracavitary administration, and direct intratumoral infusion. Drug streaming from arterial catheters leading to nonuniform distribution of drug in the infused tissue previously shown in rats and monkeys has been demonstrated in human subjects. work is in progress on the development of a physiological pharmacokinetic model for methyl mercury and inorganic mercury in the rat. Work is also in progress on the adaptation of a pharmacokinetic model for cis-- diamminedichloroplatinum(II) to other platinum-containing complexes. Increased emphasis has been placed on the pharmacokinetics of macromolecules such as monoclonal antibodies and immunotoxins.
