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The Use of BDDCS in Classifying the Permeability of Marketed Drugs

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Abstract

We recommend that regulatory agencies add the extent of drug metabolism (i.e., ≥ 90% metabolized) as an alternate method in defining Class 1 marketed drugs suitable for a waiver of in vivo studies of bioequivalence. That is, ≥ 90% metabolized is an additional methodology that may be substituted for ≥ 90% absorbed. We propose that the following criteria be used to define ≥ 90% metabolized for marketed drugs: Following a single oral dose to humans, administered at the highest dose strength, mass balance of the Phase 1 oxidative and Phase 2 conjugative drug metabolites in the urine and feces, measured either as unlabeled, radioactive labeled or nonradioactive labeled substances, account for ≥ 90% of the drug dosed. This is the strictest definition for a waiver based on metabolism. For an orally administered drug to be ≥ 90% metabolized by Phase 1 oxidative and Phase 2 conjugative processes, it is obvious that the drug must be absorbed. This proposal, which strictly conforms to the present ≥ 90% criteria, is a suggested modification to facilitate a number of marketed drugs being appropriately assigned to Class 1.

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Abbreviations

BCS:

Biopharmaceutics Classification System

BDDCS:

Biopharmaceutics Drug Disposition Classification System

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ACKNOWLEDGEMENTS

This work was supported in part by NIH Grant GM 075900.

Author information

Authors and Affiliations

  1. Department of Biopharmaceutical Sciences, University of California San Francisco, 533 Parnassus Avenue, Room U-68, San Francisco, California, 94143-0446, USA

    Leslie Z. Benet

  2. Department of Pharmaceutics, University of Michigan, College of Pharmacy, Ann Arbor, Michigan, 48109-1065, USA

    Gordon L. Amidon

  3. RIVM-National Institute for Public Health and the Environment, Bilthoven, The Netherlands

    Dirk M. Barends

  4. Department of Pharmacy, Division of Biopharmaceutics and Pharmacokinetics, University of Uppsala, S-75123, Uppsala, Sweden

    Hans Lennernäs

  5. Department of Pharmaceutical Sciences, University of Maryland, School of Pharmacy, Baltimore, Maryland, 21201, USA

    James E. Polli

  6. North Potomac, Maryland, 20878, USA

    Vinod P. Shah

  7. Pharmaceutics Division, College of Pharmacy, University of Texas at Austin, Austin, Texas, 78712, USA

    Salomon A. Stavchansky

  8. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Science, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA

    Lawrence X. Yu

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  1. Leslie Z. Benet
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  4. Hans Lennernäs
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  8. Lawrence X. Yu
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Correspondence to Leslie Z. Benet.

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Opinions expressed in this report are those of the authors. For those authors affiliated with regulatory agencies (DMB & LXY) the opinions do not necessarily reflect the views or policies of the regulatory agencies.

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Benet, L.Z., Amidon, G.L., Barends, D.M. et al. The Use of BDDCS in Classifying the Permeability of Marketed Drugs. Pharm Res 25, 483–488 (2008). https://doi.org/10.1007/s11095-007-9523-x

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  • DOI: https://doi.org/10.1007/s11095-007-9523-x

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