Saris S D, Piraino A J, Morgan J M, Hirschhorn W L, Meidl E, Schaffer A V
Clinical Research Unit, Medical College of Pennsylvania, Philadelphia 19129.
Clin Pharmacol Ther. 1993 Jul;54(1):65-9. doi: 10.1038/clpt.1993.112.
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.
3-甲基-2-(3-吡啶基)-1-吲哚辛酸（CGS-12970）是一种可逆性血栓素合酶抑制剂，在人体初步试验中发现它能降低血清尿酸水平。我们的临床研究部门对20名健康男性志愿者进行了研究，他们每隔12小时接受两剂CGS-12970（每天两次，剂量分别为100、200、300或400毫克）。4名受试者接受安慰剂作为对照。血清尿酸浓度降低了34%至47%。首次给药后12小时内，尿酸的尿排泄量增加了28%至134%。最后一剂后24小时内，尿酸的尿排泄量恢复到基线水平。对牛奶油黄嘌呤氧化酶抑制活性的体外研究表明，CGS-12970或其代谢产物CGS-12961对黄嘌呤氧化酶的抑制作用极小。CGS-12970似乎是一种有效的可逆性促尿酸排泄剂。我们推测，促尿酸排泄作用可能归因于CGS-12970的酸性性质，而非其对血栓素合酶的抑制作用。
