Abstract
We have recently shown that the introduction of a nitroxybutylester moiety 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 Flurbi-NO. Here we have investigated whether this is associated with a reduction in platelet aggregability in vivo, as assessed in a mouse model of thromboembolism and a rat model of platelet aggregation, and found in both models that Flurbi-NO is more potent than flurbiprofen at inhibiting collagen-induced platelet aggregation. Further in vitro studies using human washed platelets and cells in culture suggest that this is due to the release of NO from Flurbi-NO following the action of (possibly plasma) esterases. Together with our earlier data, these results strongly suggest that Flurbi-NO and other members of this class of drugs, have particular potential as antithrombotic agents devoid of gastrointestinal side effects.
Original language | English |
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Pages (from-to) | 73-81 |
Journal | Thrombosis Research |
Volume | 79 |
DOIs | |
Publication status | Published - 1995 |