FLURBINITROXYBUTYLESTER - A NOVEL ANTIINFLAMMATORY DRUG HAS ENHANCED ANTITHROMBOTIC ACTIVITY

We have recently shown that the introduction of a nitroxybutylester mo iety into flurbiprofen, to form Flurbi-NO, results in a compound with markedly reduced undesired effects in the gastrointestinal tract. This effect has been shown to be linked to nitric oxide release from the F lurbi-NO. Here we have investigated whether this is associated with a reduction in platelet aggregability in vivo, as assessed in a mouse mo del of thromboembolism and a rat model of platelet aggregation, and fo und in both models that Flurbi-NO is more potent than flurbiprofen at inhibiting collagen-induced platelet aggregation. Further in vitro stu dies using human washed platelets and cells in culture suggest that th is is due to the release of NO from Flurbi-NO following the action of (possibly plasma) esterases. Together with our earlier data, these res ults strongly suggest that Flurbi-NO and other members of this class o f drugs, have particular potential as antithrombotic agents devoid of gastrointestinal side effects.