Administration to man of UK-37,248-01, a selective inhibitor of thromboxane synthetase.

Pairs of healthy male volunteers received single oral doses (5-200 mg) of UK-37,248-01, a selective thromboxane synthetase inhibitor. Measurement of total thromboxane B2 (TXB2) concentrations in serum from venous blood showed that production of TXB2 was inhibited in a dose-related manner, with peak inhibition 1 h after doses of 50 mg and above. After 100 mg and 200 mg doses TXB2 production was inhibited by more than 90% at 1 h and about 50% at 6 h. Plasma drug assays confirmed oral absorption. About one-third of the dose was excreted unchanged in the urine, most within the first 4 h. Small and transient increases in bleeding time (within the normal range, except in one subject) were seen after the 50, 100, and 200 mg doses and corresponded to low levels of TXB2 production; whole blood clotting time was unchanged. There were no clinically relevant changes in heart rate or blood-pressure, other than a transient reduction in standing systolic blood-pressure and heart rate in one subject who received 200 mg. There were no side-effects and routine laboratory tests revealed no important abnormalities.