Reconciling Human-Canine Differences in Oral Bioavailability: Looking beyond the Biopharmaceutics Classification System.

Abstract

The extrapolation of oral bioavailability (F) information between dogs and humans has had an important role in the drug development process, whether it be to support an assessment of potential human pharmaceutical formulations or to identify the bioavailability challenges that may be encountered in dogs. Accordingly, these interspecies extrapolations could benefit from a tool that helps identify those drug characteristics consistent with species similarities in F. Our initial effort to find such a tool led to an exploration of species differences as it pertained to the biopharmaceutics classification system (BCS). However, using a range of compounds, we concluded that solubility and permeability alone could not explain interspecies inconsistencies in estimates of F. Therefore, we have now extended our evaluation to include canine versus human comparisons of F based upon the biopharmaceutics drug disposition classification system (BDDCS) and the extended clearance classification system (ECCS). Using the same data as that in our initial BCS assessments, we conclude that although neither the BDDCS nor the ECCS can reliably improve our ability to determine when F will be similar in humans and dogs, the ECCS provides a mechanism to help define possible causes for observed human-canine inconsistencies.