Back to the Top
We have not been able to find a reference to a method which we have
applied to evaluate the effects of multiple dosing in a Phase 1 study.
The study had a once daily dosing schedule at a fixed dose for 14
consecutive days. The compound has a very long terminal half-life
which can only be measured either after higher single doses than
applied in this study or after repeated dosing at lower levels. As
the tail cannot be adequately measured after intake of the first
single dose, AUCinf for Day 1 cannot be calculated, and the standard
comparison of AUCtau for Day last to AUCinf for Day 1 cannot be made.
As a way around this problem, we have corrected AUCtau for residual
exposure due to previous dosing by subtracting AUC24-48 after the
last dose. This corrected AUCtau value is the AUC which has resulted
solely from dosing on Day 14. And we have compared this with AUC0-24
for Day 1. In our recollection, this method has been mentioned in a
publication in the past, but we don't remember in which journal or when.
Thanks in advance for any help in this,
Kendle International B.V.
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (email@example.com)