The activity of AA-193, a new uricosuric agent, in animals.
A new uricosuric agent, 5-chloro-7,8-dihydro-3-phenylfuro[2,3-g]-1,2-benzisoxazole-7-carbo xylic acid (AA-193), was compared with other uricosurics in the rat, mouse and cebus monkey. In rats, probenecid and tienilic acid increased the urate excretion, but benzbromarone did not have the uricosuric activity. Thus, the presecretory reabsorption of urate is probably dominant in rats. We found that in rats AA-193 was the most potent uricosuric tested. In mice, probenecid not only had so-called paradoxical actions but stimulated urinary urate wasting after administration of pyrazinamide. These data suggest that the renal transport system of urate in the mouse is similar to that in man. AA-193 as well as benzbromarone enhanced the urate excretion dose-dependently, but the effects were different in pyrazinamide suppression tests in mice. In cebus monkeys, the uricosuric and hypouricemic effects of AA-193 were more potent than those of probenecid and similar to those of tienilic acid, but less than those of benzbromarone. Benzbromarone had a considerable role in postsecretory reabsorption in the monkey. These results suggest that AA-193 is a new class of uricosuric agent that controls the renal reabsorption of filtered urate particularly.
Dan
T
T
Chugai Pharmaceutical Co., Ltd., Fuji Gotemba Research Laboratories, Shizuoka, Japan.
Koga
H
H
Onuma
E
E
Tanaka
H
H
Sato
H
H
Aoki
B
B
D000818:Animals; D002428:Cebus; D004305:Dose-Response Relationship, Drug; D006074:Gout Suppressants / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051379:Mice; D011718:Pyrazinamide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014527:Uric Acid / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000652:urine; D014528:Uricosuric Agents / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism
D006074:Gout Suppressants; D007555:Isoxazoles; D014528:Uricosuric Agents; C062919:AA 193; D014527:Uric Acid; D011718:Pyrazinamide