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Reconciling Human-Canine Differences in Oral Bioavailability: Looking beyond the Biopharmaceutics Classification
Marilyn N Martinez1, Ayman El-Kattan2, Elias Awji3
1Office of New Animal Drug Evaluation, Center for Veterinary Medicine, Rockville, Maryland, USA. marilyn.martinez@fda.hhs.gov.
The AAPS Journal
|August 10, 2019
Summary
Predicting oral bioavailability (F) across species is crucial for drug development. While the biopharmaceutics drug disposition classification system (BDDCS) and extended clearance classification system (ECCS) were explored, only ECCS aids in understanding human-canine bioavailability differences.
Area of Science:
- Pharmacokinetics
- Drug Development
- Comparative Pharmacology
Background:
- Accurate extrapolation of oral bioavailability (F) between dogs and humans is vital for drug development.
- Existing models like the biopharmaceutics classification system (BCS) have limitations in explaining interspecies F variations.
- Identifying drug characteristics for similar F in dogs and humans requires refined predictive tools.
Purpose of the Study:
- To evaluate the utility of the biopharmaceutics drug disposition classification system (BDDCS) and the extended clearance classification system (ECCS) for predicting interspecies oral bioavailability (F).
- To assess the ability of BDDCS and ECCS to explain inconsistencies in oral bioavailability (F) between canine and human subjects.
- To identify a framework for understanding species-specific bioavailability challenges in drug development.
Main Methods:
- Comparative analysis of oral bioavailability (F) data in dogs and humans.
- Application of the biopharmaceutics drug disposition classification system (BDDCS) to categorize compounds.
- Utilization of the extended clearance classification system (ECCS) to assess drug disposition differences.
Main Results:
- Neither BDDCS nor ECCS reliably predicted similar oral bioavailability (F) between dogs and humans across a range of compounds.
- Solubility and permeability alone, as assessed by BCS, were insufficient to explain interspecies F inconsistencies.
- The ECCS framework offered insights into potential reasons for observed human-canine differences in oral bioavailability (F).
Conclusions:
- Current classification systems (BCS, BDDCS, ECCS) have limitations in reliably predicting interspecies oral bioavailability (F) similarity.
- The ECCS provides a valuable mechanism for investigating the causes of human-canine bioavailability discrepancies.
- Further development of predictive models is needed to improve interspecies extrapolation in drug development.
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