Metabolic Fate of a Benzoylphenylurea Derivative, HO-221. (IV). Absorption, Metabolism and Excretion in Dogs.

Abstract

The absorption, metabolism and excretion of benzoylphenylurea derivative, HO-221 in male dogs were studied after oral administration of 14C(Pc)-HO-221 at a dose of 25 mg/kg. 1. The radioactivity levels in the plasma reached a maximum at 24 hr after administration and declined with a half-life of 220 hr up to 120 hr. 2. The excretion of radioactivity in the urine and feces was 0.2 and 98.2% of the dose, respectively, within 120 hr after administration. The excretion of radioactivity in the bile was 0.5% of the dose within 48 hr after administration. 3. The protein binding ratios in vitro and vivo were more than 99% both in the case of dog or human plasma, but binding was reversible. 4. The parent compound was a major component in the plasma. M5 and M6 were also observed. Polar metabolites in origin accounted for about 80% of the radioactivity in the urine. The parent compound was a major component in the feces and M5 was detected as a minor metabolite. Polar metabolites in origin were major in the bile, part of which were conjugates.