Document Detail


Hypouricemic and uricosuric actions of AA-193 in a hyperuricemic rat model.
MedLine Citation:
PMID:  8289669     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In normal rats, consecutive administrations of AA-193 for 7 days maintained the dose-dependent uricosuric activity without significant changes of the plasma urate level. In clearance studies, AA-193 produced an increase in the fractional excretion of urate (FEua) namely an inhibition of the net urate reabsorption in the nephron, which was probably dependent on the plasma concentration of the agent. During in vitro studies, 1 mmol/L AA-193 had no effect on liver uricase activity and 0.2 mmol/L AA-193 did not inhibit xanthine dehydrogenase activity. Therefore, it is unlikely that AA-193 at physiologic doses has a significant effect on either the production or degradation of urate. To assess the hypouricemic effect of AA-193 derived from its uricosuric effect, we used uricase-inhibited rats produced by oxonate feeding. In the hyperuricemic rat model, consecutive administrations of AA-193 for 7 days increased urate excretion and decreased the plasma urate level. We conclude that AA-193 has a hypouricemic effect caused by increases in urate excretion in hyperuricemic rats.
Authors:
T Dan; T Yoneya; M Onoma; E Onuma; K Ozawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Metabolism: clinical and experimental     Volume:  43     ISSN:  0026-0495     ISO Abbreviation:  Metab. Clin. Exp.     Publication Date:  1994 Jan 
Date Detail:
Created Date:  1994-02-24     Completed Date:  1994-02-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0375267     Medline TA:  Metabolism     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  123-8     Citation Subset:  IM    
Affiliation:
Shizuoka Fuji Gotemba Research Laboratories, Chugai Pharmaceutical, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Dose-Response Relationship, Drug
Isoxazoles / pharmacology*
Kidney / drug effects,  physiology
Liver / enzymology
Male
Oxonic Acid / pharmacology
Rats
Rats, Wistar
Time Factors
Urate Oxidase / analysis
Uric Acid / blood*,  urine
Uricosuric Agents / pharmacology*
Xanthine Dehydrogenase / analysis
Chemical
Reg. No./Substance:
0/Isoxazoles; 0/Uricosuric Agents; 107804-48-8/AA 193; 69-93-2/Uric Acid; 937-13-3/Oxonic Acid; EC 1.17.1.4/Xanthine Dehydrogenase; EC 1.7.3.3/Urate Oxidase

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


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