Pharmacology of UK-38485 (dazmegrel), a specific inhibitor of thromboxane A2 synthetase.
Thromboxane A2 (TXA2) synthesis in rabbit and human platelet rich plasma (PRP) was inhibited in a dose-dependent manner by UK-38485 (dazmegrel) when the PRP was aggregated with collagen, arachidonic acid and ADP. The level of inhibition was time-dependent. That is, the dose-response curves shifted to lower concentrations with increasing incubation times with UK-38485 prior to addition of aggregation agents. Following bolus intravenous injections of UK-38485 in rabbits, the elimination from serum fitted a 3-exponential curve. The terminal elimination phase had a half-life of 69.8 +/- 3.8 min. Oral treatment of rabbits with UK-38485 for 2 weeks showed that animals with serum concentrations of 0.358 +/- 0.091 microgram/ml of the inhibitor had TXA2 synthesis inhibited in serum by 83.8 +/- 7.1%. This corresponded to animals which were treated with 20 mg/kg/day of the inhibitor.
Rebec
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Cleveland Research Institute, Ohio 44115.
Skrinska
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D000284:Administration, Oral; D000818:Animals; D006207:Half-Life; D006801:Humans; D007093:Imidazoles / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D013928:Thromboxane A2 / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D007202:Indicators and Reagents; C039242:dazmegrel; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase