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The metabolic disposition of DQ-2556 was studied in rats, rabbits, dogs, and monkeys after an intravenous administration of 20 mg of 14C-labeled drug per kg of body weight. The serum data were analyzed by the two-compartment open model. The mean half-lives for the drug in serum at excretion phase were 18.1, 54.4, 21.8, and 63.6 min in rats, rabbits, dogs, and monkeys, respectively. The volume of distribution and total body clearance ranged from 0.18 to 0.30 liter/kg and 0.065 to 0.45 liter/h/kg, respectively. This compound was distributed to the tissues rapidly and well, especially to the kidney, trachea, liver, thyroid, skin, and lung. Tissue concentrations declined rapidly in a few hours and then very slowly. However, no accumulation was observed in any tissues. The results of a protein-binding study by ultracentrifugation indicated that DQ-2556 was 20 to 30% bound to serum proteins in animals and its affinity was low. Almost 90% of the administered radioactivity was excreted into urine in all species. Biliary excretion in rats was 3.1% of the dose. Nearly 70% of the dose or more was excreted into urine as unchanged drug, and the amounts of urinary metabolites were small except in rabbits, in which substantial amounts of polar metabolites were detected.

Metabolic disposition of DQ-2556, a new cephalosporin, in rats, rabbits, dogs, and monkeys