Document Detail


Depletion of hepatic UDP-glucuronic acid by drugs that are glucuronidated.
MedLine Citation:
PMID:  3081704     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Salicylamide, clofibric acid, valproic acid and chloramphenicol are all known to be glucuronidated. The effects of these compounds on the hepatic concentration of UDP-glucuronic acid, the cosubstrate for glucuronidation, were studied in mice and found to lower hepatic UDP-glucuronic acid in a dose- and time-dependent fashion. Valproic acid, chloramphenicol, salicylamide and clofibric acid depleted hepatic UDP-glucuronic acid significantly at dosages as low as 0.5, 0.5, 0.75 and 4.0 mmol/kg, respectively. Hepatic UDP-glucuronic acid was decreased by 90% by valproic acid, 91% by chloramphenicol, 98% by salicylamide and 41% by clofibric acid (after dosages of 4, 2, 1 and 5 mmol/kg, respectively). UDP-glucuronic acid was depleted maximally by 15 after drug administration. Salicylamide also was used as a model compound to study the effect of drug loading on the hepatic concentrations of UDP-glucose and glycogen, precursors of UDP-glucuronic acid. It was found that, in addition to UDP-glucuronic acid, salicylamide (4 mmol/kg) also depleted UDP-glucose and glycogen by about 50%. These data suggest that large drug loads cause an increase flux through the glucuronic acid pathway and that hepatic UDP-glucuronic acid is consumed more rapidly than it is produced.
Authors:
S R Howell; G A Hazelton; C D Klaassen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  236     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1986 Mar 
Date Detail:
Created Date:  1986-04-18     Completed Date:  1986-04-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  610-4     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Chloramphenicol / pharmacology
Clofibric Acid / pharmacology
Dose-Response Relationship, Drug
Glucuronates / metabolism*
Liver / analysis,  drug effects,  metabolism*
Liver Glycogen / analysis
Male
Mice
Salicylamides / pharmacology
Time Factors
Uridine Diphosphate Glucose / analysis
Uridine Diphosphate Glucuronic Acid / metabolism*
Uridine Diphosphate Sugars / metabolism*
Valproic Acid / pharmacology
Grant Support
ID/Acronym/Agency:
ES-03192/ES/NIEHS NIH HHS; ES-07079/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Glucuronates; 0/Liver Glycogen; 0/Salicylamides; 0/Uridine Diphosphate Sugars; 133-89-1/Uridine Diphosphate Glucose; 2616-64-0/Uridine Diphosphate Glucuronic Acid; 56-75-7/Chloramphenicol; 65-45-2/salicylamide; 882-09-7/Clofibric Acid; 99-66-1/Valproic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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