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I have a question for our Board:
After a single oral dose of a novel drug, a metabolite shows
noticeable delay of onset and the terminal phase of the metabolite is
significantly parallel to the parent terminal phase on a semilog plot.
The AUC o-inf of the metabolite is 20% of the AUC 0-inf of the parent.
Here's the problem.
After multiple oral dosing of the parent, and the metabolite still
shows a first dose onset delay, ...after 13 total multiple doses, the
parent shows negligible accumulation after multiple dosing (because of
a short half life), but the metabolite accumulates at least 4 fold (on
Taking it one step further, looking just at the last dose profile, the
metabolite mirrors the profile of the parent (i.e., the terminal phase
is as short as the parent, and even the onset portion of the curve is
in parallel with the parent).
Any thoughts on what could be happening (in the absence of IV dosing
Thanks in advance.
SHAWN SPENCER, PhD.
Assistant Professor of Biopharmaceutics
Dyson Bldg., Rm 227
College of Pharmacy and Pharmaceutical Sciences
Florida A&M University
Tallahassee, FL 32307
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