Are we doing too many animal biodisposition investigations before phase I studies in man? A re-evaluation of the timing and extent of ADME studies.

This commentary attempts to re-evaluate, from a scientific standpoint, the timing and usefulness of undertaking detailed kinetic and metabolic studies in many animals from several species, and extrapolating the findings to man. This reappraisal is now possible due to the conditional acceptance of harmonised guidelines on toxicokinetics at ICH2 in Orlando in 1993, the results from which can provide much of the information that is required to design and validate safety studies and to extrapolate exposure or safety margins to man.