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. A pharmacokinetic model has been published for the pharmacokinetics of methyl mercury and inorganic mercury derived from it by demethylation in the growing rat. Preliminary consideration has been given to the pharmacokinetics of IBZM to include bound, free, and metabolite concentrations in relevant tissues. Work is well advanced on the development of a pharmacokinetic model for topotecan in the Rhesus monkey. Important features of the model include the reversible opening of the topotecan lactone to an hydroxy acid form, and transport between the plasma and the cerebrospinal fluid. Other research on regional therapy has included discussion of a draft clinical protocol for the administration of AZT into the cerebrospinal fluid for the treatment of AIDS dementia and related transport studies in the rat brain. A draft chapter on intraperitoneal drug administration has been prepared, and calculations suggest that absorption of drugs directly into the surface of the liver may be quantitatively more important than was previously recognized.
