Multiple dose trial of the thromboxane synthase inhibitor furegrelate in normal subjects

Summary Furegrelate sodium, a pyridinyl derivative thromboxane synthase inhibitor, was evaluated for its effects on thromboxane synthesis in normal volunteers after multiple dose administration. Twenty-four subjects were randomized to 200, 400, 800 or 1600 mg furegrelate or placebo treatment BID for 4 1/2 days. Furegrelate (800 or 1600 mg) significantly inhibited thromboxane synthesis throughout the dosing interval as assessed by thromboxane B₂ generation from platelet-rich plasma challenged with arachidonic acid or from serum. Platelet aggregation was inhibited, but the effect was variable and a clear dose response relationship was not apparent. Bleeding times were also variable but tended to increase at the higher doses. There was no clinically significant change in any coagulation parameters or in any safety laboratory evaluations. Peak serum concentrations occurred approximately 1 h after dosing; t_1/2k_e was approximately 2 h. There was no significant change in furegrelate's effects or pharmacokinetics over time (ie. Day 1 vs Day 5).