Abstract
Understanding of the relationship of oral absorption and oral bioavailability (BA) of potential drug candidates between animals and humans is important in drug discovery and development. Despite the similarities in monkeys and humans, marked differences have been found in oral BA for many drugs. Because BA values determine the therapeutic potential of a drug, caution should be exercised in extrapolating data obtained in animals, especially in monkeys as it may not predict that in humans. There have been many improvements in predicting human pharmacokinetics, which are determined by functions of metabolic enzymes and transporters, based on a combination of animal, in vitro, and in silico (e.g., physiologically-based pharmacokinetic) models, but failures still occur.
Microdosing studies in humans potentially have an important place in the drug development process inasmuch as they can offer an early determination of the pharmacokinetic properties of a compound and thus assist in the selection of those drug candidates that possess optimal disposition properties for further evaluation in the clinic. This strategy allows early evaluation of systemic clearance, oral bioavailability, and excretion ratio into urine as well as sources of intersubject variability and questions of specific metabolite formation.
