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Can someone please let me know about any information
and/or references on in-vivo induction and inhibition
studies in rats?
Thanks
Ananda
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Dear Ananda,
Here are some references for In-vivo induction.
Lake BG, Renwick AB, Cunninghame et al (1998) Comparison of the effect
of
some CYP3A and other enzyme inducers on replicative DNA synthesis and
cytochrome P450 isoforms in rat liver. Toxicology, 131: 9-20.
Meredith C, Scott MP, Renwich et al (2002) Studies on the induction of
rat
hepatic CYP1A, CYP2B, CYP3 and CYP4A subfamily form mRNAs in vivo and in
vitro using precision-cut rat liver slices.
Xenobiotica, 33(5): 511-527.
Hope this will help.
Xin Tong
DMPK/PD, Vernalis
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Has anyone out there come across a cunning "non-destructive" way of
studying
enzyme induction/inhibition in vivo?
Kim
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Kim,
A common method is to dose with the putative inducer or inhibitor
for a suitable period of time and then test with a probe substrate
(or cocktail of such substrates) for the affected enzyme(s). This
approach is suitable for use in animals or man. If you need
non-invasive, as opposed to non-destructive, methodology you could
look at urinary 6beta-hydroxycortisol (sensitive to CYP3A induction)
or use radiolabeled substrates compatible with breath tests.
All the very best,
Bernard
Bernard Murray, Ph.D.
Senior Pharmacologist
Drug Metabolism, PCS, PPD, GPRD, Abbott Laboratories, Chicago, USA
Bernard.Murray.at.abbott.com
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Kim,
what do you mean with nondestructive? Of course, you can study
inhibition and induction e.g.in clinical trials with sensitive victim
drugs (e.g. midazolam or alprazolam for CYP3A), but I think you mean
something else, but what?
Dietrich
ECD, Pharmacokinetics
Pharma Novartis Basel
Tel 0041 61 3241789
dietrich.tuerck.-at-.pharma.novartis.com
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Not enough is known about enzyme system responses to changes in
environmental conditions and diet, for example. This severely limits
our
ability to interpret the significance of changes to enzyme systems
caused by
chemicals. So I was thinking of a broadly applicable technique that
might
help to understand these "natural" fluctuations in animals (without the
need
to kill them to get each datapoint) or man. I'm thinking mainly of liver
enzyme systems.
Kim Travis
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)