Metabolic Fate of a Benzoylphenylurea Derivative, HO-221. (I). Absorption, Distribution and Excretion in Rats after Single Administration.

Abstract

The absorption, distribution and excretion of a benzoylphenylurea derivative, HO-221 were studied in rats after single oral administration of 14C(Pc)-HO-221 or 14C(Pn)-HO-221. 1. The radioactivity level in the blood reached a maximum at 12 hr after administration of 14C(Pc)-HO-221 to male and female rats at a dose of 25 mg/kg. The absorption ratio was about 9 % as caluculated from the mass balance study. The Cm and AUC were not dose-related at the dose range of 8.3 to 25 mg/kg. The absorption from the digestive tracts tended to decrease by fasting. The Cmax and AUC derived from 14C(Pn)-HO-221 were both 2 times higher than those derived from 14C(Pc)-HO-221. 2. The radioactivity levels in the fat, liver, brown fat, adrenal gland and Harderian gland were high after administration of 14C(Pc)-HO-221 to male and female rats. The radioactivity in the tissues was eliminated rapidly, except the kidney and liver. 3. The excretion of radioactivity in the urine and feces was about 2 and 95% of the dose, respectively, within 120 hr after administration of 14C (Pc)-HO-221 to male and female rats. The excretion of radioactivity in the bile was about 5% of the dose. About 30% of the biliary excreta (1% of the dose) was re-absorbed. The excretion of radioactivity in the urine was 3 % of the dose within 120 hr after administration of 14C(Pn)-HO 221. 4. The protein binding ratios in vitro and vivo were more than 99% but the binding was reversible.