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 has continued with emphasis on intra-arterial and intracavitary administration. This has led to spatially-distributed descriptions of the processes. On theoretical bases, depth of penetration of drugs into tissue adjacent to cavities can vary considerably, depending on the intratissue diffusivity, capillary permeability-area product and rate of irreversible reaction with tissue. Drug streaming from arterial catheters appears to be a frequent problem leading to nonuniform distribution of drug in the infused tissue and compromising studies of toxicity and therapeutic effect. 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.
