DISTRIBUTION EXCRETION METABOLISM AND LOCALIZATION OF A NEW ANTI-INFLAMMATORY DRUG - NIFLUMIC ACID LABELLED WITH 14C

The metabolism of the 14C-niflumic acid† † Nifluril® UPSA, 157 Av. des Grésillons, Gennevilliers, France. specific activity 16 mc/mM has been studied in the rat, after intraperitoneal administration. With doses of 50 mg/kg, the blood level is of 75 μg/ml at the 1st hr, and of 6 μg/ml at the 24th hr. The product is nearly all bound to the plasma proteins. The liver retains, after 1 hr, 4 per cent of the injected activity and the stomach 0.5 per cent only traces (0.08 per cent) have been detected in the brain. The technique of autoradiography in the mouse, after administration of the product per os and i.p. confirms these results. About 5 per cent of 14CO2 is found with respect to the injected activity, after 12 hr. The radioactivity eliminated in the urine is about 2 per cent of the injected activity after 1 hr, reaches 30 per cent at the 12th hr, is practically completed after 24 hr. The radioactivity found in the faeces is generally of the order of 0.01 per cent. Five catabolites were found by paper chromatography in the urine. Niflumic acid is not eliminated unchanged, and the greatest quantity appears to be conjugated glucuronide. One of the catabolites, after paper Chromatographie study in various systems, corresponds to 2-aminonicotinic acid. Possible metabolic pathways of the Niflumic acid discussed. © 1969.