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The following message was posted to: PharmPK
Dear all,
Does anybody know a broad spectrum inhibitor for UGTs?
Thank you very much!
Thomas
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The following message was posted to: PharmPK
Thomas,
Thanks for your message. Valproate is reported as a demonstrated
broad-spectrum inhibitor of UGTs. Bilirubin is reported as an
inhibitor of UGT1A4, and selected HIV protease inhibitors (e.g.
atazanavir) have been reported as inhibitors of UGT1A1.
Best Regards,
Jim Schmidt
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Thomas,
For glucuronidation-selective inhibition I have used borneol. Typical
protocols involve using e.g. 1 mM in hepatocytes. I also understand
that it can be used in vivo (e.g. 300 mg/kg). For general conjugation
inhibition I have used salicylamide (e.g. 3 mM) and, again, I have seen
this used in vivo (e.g. 250 mg/kg as a co-dose). Other people have
used benzoic acid. I haven't seen any formal testing of the breadth
of inhibition by these compounds (e.g. borneol is a particularly good
substrate for UGT2B12) but I assume at these concentrations that it
will affect most/all UGT enzymes. Salicylamide will definitely inhibit
sulphation as well as glucuronidation.
I hope that this helps.
All the very best,
Bernard
--
Bernard Murray, Ph.D.
Research Investigator/Scientific Leader
Drug Metabolism, PCS, PPD, GPRD, Abbott Laboratories, Chicago, USA
Bernard.Murray.at.abbott.com
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Dear Bernard,
I agree with you regarding the use of salicylamide as a broad
glucuronidation inhibitor.
However, did you check whether this compound also inhibit or activate
phase
I enzymes, mainly CYPs ?
Because we encountered such problems...
Best regards
Nathalie
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The following message was posted to: PharmPK
Probenecid and Ibuprofen are known inhibitors of UGT. Not very sure of
Ibuprofen though.
Regards,
Prasad Tata
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)