Back to the Top
The following message was posted to: PharmPK
As far as attenuating, I'm not so sure, but it certainly can amplify
Greater metabolism means lower bioavailability, which in turn means
change in total bioavailability is a bigger fraction than if
is higher. In the extreme, trying to match a reference that is 100%
bioavailable is much easier than trying to match one that is 1%
Gut wall metabolism and transporters can create difficulties
bioequivalence when the enzyme or transporters are not uniformly
along the gut wall (3A4, 2D6, PepT1, Bile acid carrier, etc.).
vivo release rates will result in different concentrations in the
high expression, in turn resulting in modifying bioavailability.
To add to the difficulty, polymorphism can cause significant variance
subjects for some enzymes and transporters, requiring more subjects to
achieve sufficient power for a BE study.
Our GastroPlus(tm) software simulates all of the complex interactions
these phenomena. Its Virtual Trials capability can help customers to
conducting bioequivalence studies that would have failed when such
mechanisms are involved, and to select the number of subjects needed to
provide an acceptable probability of success.
Chairman & CEO
Simulations Plus, Inc. (AMEX: SLP)
1220 W. Avenue J
Lancaster, CA 93534-2902
Phone: (661) 723-7723
FAX: (661) 723-5524
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (firstname.lastname@example.org)