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The Use of BDDCS in Classifying the Permeability of Marketed Drugs

2008; Springer Science+Business Media; Volume: 25; Issue: 3 Linguagem: Inglês

10.1007/s11095-007-9523-x

1573-904X

Leslie Z. Benet, Gordon L. Amidon, D.M. Barends, Hans Lennernäs, James E. Polli, Vinod P. Shah, Salomon Stavchansky, Lawrence X. Yu,

Biosimilars and Bioanalytical Methods

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.