THE ANTIPLATETLET ACTIONS OF FR122047, A NOVEL CYCLOOXYGENASE INHIBITOR

The anti-platelet actions of oxyphenyl)-2-thiazoyl)carbonyl]-4-methylp iperazine hydrochloride (FR122047) were investigated in vitro and in v ivo. FR122047 was 100 times more potent than aspirin against arachidon ic acid- and collagen-induced human and guinea-pig platelet aggregatio n in vitro. Its actions on platelets were a result of cyclooxygenase i nhibition. The single oral dose of FR122047 inhibited arachidonic acid - and collagen-induced aggregation with an ED50 of 280 mug/kg and 530 mug/kg, respectively, in guinea-pigs. The anti-platelet action was aug mented 5-10 times by repeated administration for 4 days. At 1 mg/kg th e inhibitory actions were prolonged for 48 h and the drug concentratio n was < 0.1 ng/ml in platelet-poor plasma at 24 h and 0.282 ng/ml in p latelet-rich plasma at 48 h. The safety margin in rats (minimum ulcero genic dose/ED50 for anti-platelet aggregation) of FR122047 was more th an 70, while that of aspirin was only 1.2. These results indicate that FR122047 is concentrated in platelets and may be a useful anti-platel et agent.