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The following message was posted to: PharmPK
Dear All,
I am looking at compound which is extensively metabolized by Phase II (especially glucuronide conjugation and sulfation) metabolic pathways.
Can anyone suggest me in vivo inhibitors (can be non specific/specific) that can be used in rats to increase the bioavailability of the compound.
Thanking you in anticipation,
Regards,
Ramachandra.
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The following message was posted to: PharmPK
You could try probenecid
Cheers
Hans
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Hi Ramchandra,
You can also try aminobenzotriazole (ABT) which is suicidal CYP inhibitor and extensively used to increase the bioavailability in preclinical PK studies.
You can refer following article:
The Use of the Suicide CYP450 Inhibitor ABT for Distinguishing Absorption and Metabolism Processes in In-vivo Pharmacokinetic Screens
GARY W. CALDWELL, DAVID M. RITCHIE, JOHN A. MASUCCI, WILLIAM HAGEMAN, CARLOS COTTO, JEFFREY HALL, BECKI HASTING AND WILLIAM JONES
Johnson & Johnson Pharmaceutical Research and Development, L.L.C.
Drug Discovery, Spring House, USA
Regards
Sachin More
Sai Advantium Pharma Ltd,
Pune
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Dear Ramachanddra,
borneol should be one of them; even atazanavir also, salicylamide; probenecid and clofibric acid (for acyl glucuronidation inhibitor)
with regards
sagnik
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Sangana,
Known UGT and SULT inhibitors are not as selective as the ones we know for CYPs.
Few examples of UGT inhibitors:
UGT1A1: Atazanavir
UGT1A6: alpha-napthol, 4-t-butyl phenol
UGT1A7:TCDD
UGT1A8: 3-MC
UGT2B7:AZT, OXAZEPAM, FLUNITRAZEPAM
UGT2B13: 4-OH-BIPHENYL
Sults (Pacifici and coughtrie, 2005):
Sult1A1: DCNP
SULT1E1: HPCBs
NSIADs, flavones, quercetin
Note: another way to globally inhibit Sults in rodents is through PAPS depletion, which is easily depleted for example in the case of acetaminophen (Klaassenn etal, 1994)
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