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The following message was posted to: PharmPK
Dear PharmPK users
Dose anyone know the exact definition and mechanism of metabolite
inhibition or (product inhibition), in any kind of inhibitore and
substrate with some good references to this subject.
Thanks in advance
Amir
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The following message was posted to: PharmPK
Amir,
That is not as easy a question as it sounds. When discussing this
subject you have to be careful to distinguish between "mechanism based
inhibition", "metabolite inhibition", "time dependent inhibition",
"suicide inhibition" etc. as although they are inter-related they may
not be identical. Also, you haven't specified whether you are working
at the pharmacokinetic level (and want to model the effects of such an
inhibitor) or at the enzymological level. Then, how is the inhibitory
metabolite achieving the effect? - competition?, covalent binding? (if
P450 then haem or protein?), tight/quasi-irreversible binding?, haem
destruction with binding of fragments to protein? In some cases
(rarely P450) the effects can also be heterologous in nature.
It would be helpful for you to narrow your question to mechanism,
kinetics or pharmacokinetics. As a starting point, for each of these
aspects there are excellent reviews available through Medline. The
PhRMA paper I pointed out to you in an earlier message is a good
jumping-off point. Any good text book of enzymology will cover the
kinetic aspects.
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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The following message was posted to: PharmPK
Amir:
Please look into Introduction (or Handbook) to Drug Metabolism by Gordon
Gibson or you can look into Enzyme Kinetics there you get good
references.
Prasad Tata
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)