cg100649 and Cardiovascular-Diseases

Nonsteroidal anti-inflammatory drugs (NSAIDs) elevate cardiovascular risk by disrupting cyclooxygenase-2 (COX-2)-dependent biosynthesis of prostacyclin (PGI(2)). 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-PGF(1α) (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.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Asian; Black People; Carbonic Anhydrase Inhibitors; Cardiovascular Diseases; Celecoxib; Cross-Over Studies; Cyclooxygenase 2 Inhibitors; Double-Blind Method; Epoprostenol; Female; Furans; Humans; Male; Middle Aged; Prostaglandin Antagonists; Prostaglandins; Pyrazoles; Risk Assessment; Sulfonamides; Thromboxane B2; White People; Young Adult