title: The use of BDDCS in classifying the permeability of marketed drugs.
abstract: We recommend that regulatory agencies add the extent of drug metabolism (i.e., >or=90% metabolized) as an alternate method in defining Class 1 marketed drugs suitable for a waiver of in vivo studies of bioequivalence. That is, >or=90% metabolized is an additional methodology that may be substituted for >or=90% absorbed. We propose that the following criteria be used to define>or=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 >or=90% of the drug dosed. This is the strictest definition for a waiver based on metabolism. For an orally administered drug to be >or=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>or=90% criteria, is a suggested modification to facilitate a number of marketed drugs being appropriately assigned to Class 1.
authors.affiliation: Department of Biopharmaceutical Sciences, University of California San Francisco, 533 Parnassus Avenue, Room U-68, San Francisco, California 94143-0446, USA. leslie.benet@ucsf.edu
authors.forename: Leslie Z
authors.initials: LZ
authors.lastname: Benet
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Amidon
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Barends
authors.forename: Hans
authors.initials: H
authors.lastname: Lennernäs
authors.forename: James E
authors.initials: JE
authors.lastname: Polli
authors.forename: Vinod P
authors.initials: VP
authors.lastname: Shah
authors.forename: Salomon A
authors.initials: SA
authors.lastname: Stavchansky
authors.forename: Lawrence X
authors.initials: LX
authors.lastname: Yu
mesh_terms: D000284:Administration, Oral; D017277:Drug Approval; D006801:Humans; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism*; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000145:classification* / Q000378:metabolism; D010599:Pharmacokinetics; D012995:Solubility; D013810:Therapeutic Equivalency
chemical_list: D004364:Pharmaceutical Preparations