Abstract
Thromboxane A 2 (TXA 2) 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 μg/ml of the inhibitor had TXA 2 synthesis inhibited in serum by 83.8 ± 7.1%. This corresponded to animals which were treated with 20 mg/kg/day of the inhibitor.
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