Species differences in the hepatic microsomal oxidation of nalidixic acid.
The kinetics of the conversion of nalidixic acid to the 7-hydroxymethyl derivative (M-HNA) by isolated liver microsomes of several common laboratory animal species was studied under optimal conditions. The order of activity was (from greatest activity to least): monkey greater than rabbit greater than mouse greater than rat greater than dog greater than cat. The formation of 7-HNA followed apparent Michaelis-Menton kinetics in all species except the cat; the substrate concentration at half-maximal velocity was highest with mouse microsomes, while the maximum velocity was greatest with monkey microsomes. Cat, dog, mouse and rabbit microsomes formed an additional metabolite, which was identified as 6-hydroxynalidixic acid, 1-ethyl-1,4-dihydro-6-hydroxy-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid (6-HNA); in the cat, this was the major microsomal metabolite.
D000818:Animals; D001711:Biotransformation; D002415:Cats; D004285:Dogs; D000882:Haplorhini; D066298:In Vitro Techniques; D007700:Kinetics; D008253:Macaca mulatta; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D009268:Nalidixic Acid / Q000378:metabolism*; D010084:Oxidation-Reduction; D011817:Rabbits; D051381:Rats; D013045:Species Specificity
D009268:Nalidixic Acid