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Pharmaceutical Research

, Volume 25, Issue 3, pp 483–488 | Cite as

The Use of BDDCS in Classifying the Permeability of Marketed Drugs

  • Leslie Z. Benet
  • Gordon L. Amidon
  • Dirk M. Barends
  • Hans Lennernäs
  • James E. Polli
  • Vinod P. Shah
  • Salomon A. Stavchansky
  • Lawrence X. Yu
Commentary

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.

Key Words

BCS BDDCS bioequivalence elimination pathways 

Abbreviations

BCS

Biopharmaceutics Classification System

BDDCS

Biopharmaceutics Drug Disposition Classification System

Notes

ACKNOWLEDGEMENTS

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

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Leslie Z. Benet
    • 1
  • Gordon L. Amidon
    • 2
  • Dirk M. Barends
    • 3
  • Hans Lennernäs
    • 4
  • James E. Polli
    • 5
  • Vinod P. Shah
    • 6
  • Salomon A. Stavchansky
    • 7
  • Lawrence X. Yu
    • 8
  1. 1.Department of Biopharmaceutical SciencesUniversity of California San FranciscoSan FranciscoUSA
  2. 2.Department of PharmaceuticsUniversity of Michigan, College of PharmacyAnn ArborUSA
  3. 3.RIVM-National Institute for Public Health and the EnvironmentBilthovenThe Netherlands
  4. 4.Department of Pharmacy, Division of Biopharmaceutics and PharmacokineticsUniversity of UppsalaUppsalaSweden
  5. 5.Department of Pharmaceutical SciencesUniversity of Maryland, School of PharmacyBaltimoreUSA
  6. 6.North PotomacUSA
  7. 7.Pharmaceutics Division, College of PharmacyUniversity of Texas at AustinAustinUSA
  8. 8.Food and Drug Administration, Center for Drug Evaluation and ResearchOffice of Pharmaceutical ScienceSilver SpringUSA

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