Metabolic Studies of Ornidazole in the Rat, in the Dog and in Man

Abstract

1. Ornidazole, labelled with ¹⁴C in the imidazole ring, administered orally to rats, dogs and men was largely excreted in the urine, predominantly as metabolites, with < 4% of the drug being excreted unchanged. Free and conjugated metabolites were found in the ratio of approx. 1:2.

2. The pattern of free ornidazole and metabolites was different in the three species: while ornidazole predominated in man, ornidazole and metabolite M1 in the dog, the most extensive metabolic pattern was found in the rat.

3. The following metabolites were identified: M1, 1-chloro-3-(2-hydroxymethyl-5-nitro-1-imidazolyl)-2-propanol; M2, 2-methyl-5-nitroimidazole; M3, N-(3-chloro-2-hydroxypropyl)acetamide; M4, 3-(2-methyl-5-nitro-1-imidazolyl)-1,2-propanediol; M5, acetamide.

4. The formation of metabolite M3 and M5 indicated cleavage of the imidazole ring between N-1/C-5 and C-2/C-3. Other ring scissions were not observed. Metabolites carryings a free amino group were not detected. On the basis of the structures identified, a scheme is suggested for the metabolism of ornidazole.