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 th e effect of linotroban (GAS 141443-73-4) a selective thromboxane (TXA( 2)) receptor antagonist with novel antithrombotic activity, on renal f unction 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 treatm ent. 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 signifi cant difference in GFR (glomerular filtration rate) for male and femal e rats receiving the highest dose. Linotroban is well tolerated but th e difference in renal function between male and female rats at the hig hest dose may reflect a threshold of renal tolerance.