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The following message was posted to: PharmPK
Hi, All!
I want to get the information on the techniques for estimating drug
metabolism (both in vitro and in silico)? Can someone please help me in
that regard by sending me the references, links, papers etc.?
With regards,
Jyoti
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Dear jyoti
I can tell u a bit about in vitro metabolism. You can do in vitro
mtabolism of compounds during your initial screening process. You can
use liver microsomes from rat, dog, mice and later human liver
microsomes (HLM). These can be prepared in house or can be purchased
from Gentest. You have to incubate your compound for an hour in the
system of microsomes, NADPH and the substrates and then withdraw
samples at regular intervals and then analysing them.
You can have a look at Journal named Drug Metabolism and Disposition,
it is also available on line. You can find quite few articles in it.
I think this will help.
Regards
Tausif Ahmed
Ph.D. scholar,
Department of Pharmaceutical Medicine,
Ranbaxy CPU, Hamdard University,
New Delhi-62
India
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The following message was posted to: PharmPK
Jyoti:
A recent article
Looking ahead....
In silico approaches, and in vitro and in vivo experiments to predict
induction of drug metabolism.
Drug News Perspect 16(7), September 2003 p.423-434
Hope it helps.
Best regards
Raju Poola, PhD.
Berlex, Montvile, NJ
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The following message was posted to: PharmPK
Here is the reference of one of the most recent PhRMA perspectives:
Bjornsson, T.D., et al., The conduct of in vitro and in vivo drug-drug
interaction studies: a Pharmaceutical Research and Manufacturers of
America
(PhRMA) perspective. Drug Metab Dispos, 2003. 31(7): p. 815-32.
Abstract:
Current regulatory guidances do not address specific study designs for
in
vitro and in vivo drug-drug interaction studies. There is a common
desire by
regulatory authorities and by industry sponsors to harmonize
approaches, to
allow for a better assessment of the significance of findings across
different studies and drugs. There is also a growing consensus for the
standardization of cytochrome P450 (P450) probe substrates, inhibitors
and
inducers and for the development of classification systems to improve
the
communication of risk to health care providers and to patients. While
existing guidances cover mainly P450-mediated drug interactions, the
importance of other mechanisms, such as transporters, has been
recognized
more recently, and should also be addressed. This article was prepared
by
the Pharmaceutical Research and Manufacturers of America (PhRMA) Drug
Metabolism and Clinical Pharmacology Technical Working Groups and
represents
the current industry position. The intent is to define a minimal best
practice for in vitro and in vivo pharmacokinetic drug-drug interaction
studies targeted to development (not discovery support) and to define a
data
package that can be expected by regulatory agencies in compound
registration
dossiers.
Thanks
Kishore
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