The effects of a new thromboxane synthetase inhibitor, CGS-13080, in man.

CGS-13080 is a new potent selective inhibitor of thromboxane synthetase. This study reports the results of a safety and efficacy study of single oral doses in normal healthy volunteers. The compound was well tolerated by all subjects without evidence of any adverse reactions. Serum thromboxane B2 levels (the stable metabolic product of thromboxane A2) were significantly reduced after administration of the compound, with the maximal effect of a 99 per cent reduction occurring at 0.5 and 1 hour after administration. There was a concomitant increase in PGE2 and 6-keto-PGF1 alpha (the stable metabolic product of PGI2), suggesting a shunting of cyclic endoperoxide metabolism. The apparent half-life of the compound is about 1 hour, but return to 50 per cent of the original thromboxane B2 levels was achieved between 4 and 6 hours. Platelet aggregation to collagen and bleeding times failed to demonstrate significant changes after drug administration. Bleeding times showed a slight increase 2 hours after administration of the compound.