transporters, this is open for interpretation and discussion. Once the comments
from industry and academia are received by the FDA, sometime in future it is
expected that the FDA will issue final guidance that will be agreeable to the
industry. At this juncture, the authors of this chapter believe that in the absence
of the knowledge-base on how to quantitatively assess the role of transporters on
absorption and elimination of drugs, the current draft guidance on the trigger
criteria of [I]/Ki(or IC 50 )>0.1 for the conduct of DDI studies in humans will face
conflict from the experts.
The effort needs to be continually made to better predict transporter-
mediated drug interactions by knowing the complexity of localization and
function of transporters and their interplay with Phase I and Phase II enzymes.
At this point, it is difficult to extrapolate the results fromin vitroor animal
studies to human. The challenge of understanding the quantitative significance
of transporters in drug development remains. Research focusing on the
development of methodology to delineate the contribution of major
transporters to drug disposition, the establishment of in vitro–in vivo
correlations, and understanding transporter polymorphisms will help us better
use transporter information in drug development.
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