Studies on the Metabolic Fate of Mometasone furoate (MF) (IV):Metabolism in Rats and Rabbits

Metabolic fate of 14C-MF in the rat and the rabbit was studied after subcutaneous administration at 0.5mg/kg dose. The metabolites were analyzed by two-dimensional TLC, located by autoradiography and quantitated by TLC scraping and counting of the radioactivity. Identification of the metabolites was tentatively made by co-chromatography with corresponding reference standards. Three major biotransformation pathways of MF were proposed. 1) Substitution of a 21-hydroxyl group for a chlorine : 2) 6β-Hydroxylation : 3) Defuroylation at 17 : Combination of these processes and subsequent reactions resulted in the formation of numerous metabolites.Plasma metabolites ; In the animals studied, the main component was the unchanged MF at each time point examined, and its concentration near the peak (4hr after the administration) was 13.1ng/ml in the male rat, 22.4ng/ml in the female rat and 2.8ng/ml in the male rabbit.Biliary metabolites ; About 78% of the dose was excreted in the bile within 24hr in the male and female rats. The main metabolite detected both in the free and the conjugate fraction was 17-OH compound (M-1), which amounts to 4.8% and 2.4% of dose respectively for the male, and 6.7% and 2.4% for the female. In the acidic fraction, the main metabolite was 6β-OH, 21-oic acid (M-27) in both sex and the amount found was significantly more in the male (5.9% of dose) than in the female (1.3%), indicating the sex-related differences. In the rabbit, about 19% of dose was excreted in the bile within 24hr. The main metabolite was M-1 (1.6%) in the free fraction, 6β, 21-(OH)2 compound (M-13) (0.7%)in the conjugate fractionand 21-oic acid (M-32) (0.3%) in the acidic fraction.Urinary metabolites ; In the rat, the radioactivity excreted within 24hr was 3 ?? 5 % of dose and was not so significant. A sole and main metabolite detected was 6β, 17, 21-(OH)3 compound (M-14) (about 1 % of dose). In the rabbit, about 16% of dose was excreted in the urinewithin 72hr. The main metabolite both in the free and the conjugate fraction was M-14 (1.5% and 0.2% of dose respectively).