Uricosuric effect of CGS-12970, a new thromboxane synthase inhibitor.
3-Methyl-2-(3-pyridyl)-1-indoleoctanoic acid (CGS-12970) is a reversible thromboxane synthase inhibitor that was noted to lower serum uric acid during preliminary trials in humans. Our clinical research unit studied 20 healthy male volunteers who received two doses of CGS-12970 12 hours apart (100, 200, 300, or 400 mg twice a day). Four subjects received placebo as a control. Serum uric acid concentrations decreased between 34% and 47%. Urinary excretion of uric acid increased between 28% and 134% within 12 hours of the first dose. Urinary excretion of uric acid returned to baseline within 24 hours after the last dose. In vitro study of bovine-creme xanthine oxidase inhibitor activity revealed minimal inhibition of xanthine oxidase by either CGS-12970 or its metabolite, CGS-12961. CGS-12970 appears to be a potent reversible uricosuric agent. We hypothesize that the uricosuric effect may be attributable to the acidic properties of CGS-12970 rather than to its inhibition of thromboxane synthase.
Saris
S D
SD
Clinical Research Unit, Medical College of Pennsylvania, Philadelphia 19129.
Piraino
A J
AJ
Morgan
J M
JM
Hirschhorn
W L
WL
Meidl
E
E
Schaffer
A V
AV
D000293:Adolescent; D000328:Adult; D000818:Animals; D002417:Cattle; D003404:Creatinine / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000494:pharmacology*; D012016:Reference Values; D016037:Single-Blind Method; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014527:Uric Acid / Q000097:blood* / Q000652:urine; D014528:Uricosuric Agents / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D011725:Pyridines; D014528:Uricosuric Agents; D014527:Uric Acid; C049113:3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid; D003404:Creatinine; D014969:Xanthine Oxidase; D013930:Thromboxane-A Synthase