PHARMACOKINETICS AND METABOLIC INTERCONVERSION OF INTRAVENOUS ULFINYL)ETHOXY]-N-[2-(DIETHYLAMINO)ETHYL]BENZAMIDE AND ITS SULFIDE AND SULFONE METABOLITES IN RATS

The pharmacokinetics of a new 5-hydroxytryptamine (5HT3) receptor anta gonist, ulfinyl)ethoxyl-N-[2-(diethylamino)ethyl]benzamide (ML-1035, 1 ), and its sulfone and sulfide metabolites were examined in 12 rats. E ach of these compounds (25.4 mumol/kg) was administered to rats intrav enously. Their plasma concentrations were measured by high-performance liquid chromatography. These plasma data revealed that 1, a sulfoxide , underwent interconversion with its sulfide metabolite. However, no i nterconversion was observed between 1 and its sulfone metabolite. Exam ination of mean times and additional properties of the 1/sulfide metab olite system revealed that total exposure times of 1 and the sulfide m etabolite were moderately and weakly, respectively, influenced by the metabolic interconversion process. However, the tissue distribution pr ocess strongly influenced the total exposure times of both compounds. The disposition of the sulfone metabolite of 1 was also strongly influ enced by the tissue distribution process. In addition, <3% of the intr avenous dose of 1 or the sulfide was available to the general circulat ion as the sulfone metabolite.