Studies on the Metabolic Fate of Semotiadil Fumarate (SD-3211) I: Absorption, Distribution, Metabolism and Excretion after Single Administration to Male Rats.

Abstract

The absorption, distribution, metabolism and excretion of 14C-semotiadil fumarate (14C-SD3211) were studied in rats after oral (dose ; 10mg/kg) or intravenous (1 mg/kg) single administration. 1. Concentration of radioactivity in the plasma reached the maximum level of 0.26μg/ml at 1 hr after oral administration and decreased with the half-life of 6.4hr. Concentration of SD-3211 in the plasma reached the maximum level of 0.13μg/ml at lhr, and decreased with the half-life of 3.5hr. 2. Maximum levels of radioactivity in most of tissues were reached at 2 ?? 6hr after oral administration, and high levels of radioactivity were observed in the liver, lung, kidney and harderian gland. At 96hr after oral administration, the levels in every tissue were very low compared with the maximum level. 3. Within 96hr, excretion of radioactivity was about 1.2% and 93.8% of the dose in urine and feces after oral administration, respectively. Similar excretion pattern was observed after intravenous administration, where 5.6% and 93.0% of the dose was excreted to urine and feces. 4. Within 48hr, biliary excretion of radioactivity was 87.3% of the dose after oral administration, and was 88.6% after intravenous administration. 5. In the plasma, lung and kidney, unchanged form was found about 37 ?? 58%, within 6hr after oral administration. But, in liver, unchanged form was minor component. In urine, feces and bile, unchanged form were scarcely detected.