Comparative impact on prostanoid biosynthesis of celecoxib and the novel nonsteroidal anti-inflammatory drug CG100649.
Comparative impact on prostanoid biosynthesis of celecoxib and the novel nonsteroidal anti-inflammatory drug CG100649.
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DOI：
10.1038/clpt.2012.3
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发表时间：
2012-06
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
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非甾体类抗炎药（NSAID）通过破坏环氧化酶-2（考克斯-2）依赖性前列环素（PGI2）生物合成而增加心血管风险。CG100649是一种新型NSAID，拟同时抑制考克斯-2和碳酸酐酶（CA）-I/-II。我们比较了它对前列腺素类生物合成的影响与塞来昔布，一种有目的地设计选择性抑制考克斯-2的NSAID。在一项对照、双盲随机试验中，健康志愿者（n = 23）单次口服2或8 mg CG 100649、200 mg塞来昔布或安慰剂耐受性良好。CG100649和塞来昔布均具有抑制2，3-二去甲-6-酮-PGF1 α（PGI-M）尿排泄的作用; CG100649的作用呈剂量依赖性，且比塞来昔布更持久（给药后240 h）。CG 100649和塞来昔布均未显著抑制考克斯-1依赖性前列腺素形成。给予CG100649后未检测到CA抑制，尽管其分配不对称进入红细胞。CG100649和塞来昔布都是相对选择性的考克斯-2抑制剂，但它们的作用持续时间不同。它们是否对心血管事件有类似的影响仍有待确定。
Nonsteroidal anti-inflammatory drugs (NSAIDs) elevate cardiovascular risk by disrupting cyclooxygenase-2 (COX-2)-dependent biosynthesis of prostacyclin (PGI2). CG100649 is a novel NSAID proposed to inhibit both COX-2 and carbonic anhydrase (CA)-I/-II. We compared its impact on prostanoid biosynthesis with that of celecoxib, an NSAID purposefully designed to selectively inhibit COX-2. In a controlled, double-blind randomized trial, single oral doses of 2 or 8 mg CG100649, 200 mg celecoxib, or placebo were well tolerated by healthy volunteers (n = 23). Both CG100649 and celecoxib had the effect of depressing urinary excretion of 2,3-dinor-6-keto-PGF1α (PGI-M); the effect of CG100649 was dose-dependent and more sustained (up to 240 h after the dose) than that of celecoxib. Neither CG100649 nor celecoxib significantly inhibited COX-1-dependent prostanoid formation. CA inhibition was not detected after administration of CG100649, despite its partitioning asymmetrically into erythrocytes. CG100649 and celecoxib are both relatively selective inhibitors of COX-2, but they differ in duration of action. Whether they have similar impact on cardiovascular events remains to be determined.
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DOI：
10.1111/j.1532-5415.1996.tb01437.x
发表时间：
1996-05-01
影响因子：
6.3
作者：
Kahn, S;Frishman, WH;Aronson, M
通讯作者：
Aronson, M
影响因子：
13.8
作者：
FitzGerald, Garret A.
通讯作者：
FitzGerald, Garret A.
DOI：
10.1016/j.ejpb.2009.05.009
发表时间：
2009-09-01
影响因子：
4.9
作者：
Shono, Yasushi;Jantratid, Ekarat;Dressman, Jennifer B.
通讯作者：
Dressman, Jennifer B.
影响因子：
10.4
作者：
Yu, Y.;Ricciotti, E.;Fitzgerald, G. A.
通讯作者：
Fitzgerald, G. A.
影响因子：
29.4
作者：
Fries, S;Grosser, T;Fitzgerald, GA
通讯作者：
Fitzgerald, GA