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I would appreciate it if anyone could offer an explanation for the following
experimental results from a pre-clinical study;
a two-way cross-over study in monkeys of an antibiotic administered by oral
gavage bid , 4 hours apart.
for both formulations tested, on Day 1, Cmax 2 was higher than Cmax 1 but on
Day 14 Cmax 2 was lower than Cmax 1. On Days 1 and 14 Cmax 1 was the same.
Results from a repeated dose administration study with the same formulation
administered as above, ie oral gavage bid 4 hours apart, indicated
accumulation of compound with Cmax 1, Cmax 2 and AUC all higher after
repeated dose administration.
Any ideas on what is happening here?
HUNTINGDON LIFE.SCIENCES LIMITED
http://www.huntingdon.com
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More information needed to tell what is going on:
1) half-life of the drug in monkeys
2) no of monkeys in the study
3) variability of Cmax and AUC, and size of the difference
Best regards,
Sam Liao, Ph.D.
PharMax Research
270 Kerry Lane,
Blue Bell, PA 19422
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1) On the surface it seems like the second formulation was better however
2) the first dose cold have saturated binding sites or clearance mechanisms
and may have inhited metabolic pathways. By day 14 there may have been
induction of enzymes to negate the initial effect
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)