Effects of the novel thromboxane (TXA(2)) receptor antagonist linotroban on inulin and para-aminohippuric acid clearances in the conscious male and female rat

This paper reports the results of experiments designed to determine the effect of linotroban (GAS 141443-73-4) a selective thromboxane (TXA(2)) receptor antagonist with novel antithrombotic activity, on renal function in conscious male and female rats. Linotroban was administered subcutaneously at doses of 0, 6, 24, 48 and 96 mg/kg/24 h by osmotic minipumps over 6 days. Inulin (Inutest(R)) and para-aminohippuric acid (PAH) clearances were determined on the last day of linotroban treatment. These agents were delivered by a slow release tablet planted s.c. five days after the start of the linotroban treatment. Linotroban did not significantly alter renal functions, although there was a significant difference in GFR (glomerular filtration rate) for male and female rats receiving the highest dose. Linotroban is well tolerated but the difference in renal function between male and female rats at the highest dose may reflect a threshold of renal tolerance.