The use of BDDCS in classifying the permeability of marketed drugs.
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.
Benet
Leslie Z
LZ
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
Amidon
Gordon L
GL
Barends
Dirk M
DM
Lennernäs
Hans
H
Polli
James E
JE
Shah
Vinod P
VP
Stavchansky
Salomon A
SA
Yu
Lawrence X
LX
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
D004364:Pharmaceutical Preparations