Abstract
S-1358 was rapidly absorbed, metabolized and readily excreted via urine and feces from orally dosed rats. Excretion of radioactivity was almost complete within 4 days. The radioactivity was distributed mainly in stomach, intestines, liver and kidneys. It seems that S-1358 and its metabolites do not persist in organs and tissues following a single oral dosing.
Major urinary metabolites of the benzyl-labeled S-1358 were p-(1, 1-dimethyl-2-hydro-xyethyl) benzyl methyl sulfide [B], p-(1, 1-dimethyl-2-hydroxyethyl) benzyl methyl sulfone [A], p-(1-methyl-l-carboxylethyl) benzyl methyl sulfide [D], p-(1-methyl-l-carboxylethyl) benzyl methyl sulfone [C] and their glucuronide conjugates. Fecal metabolites were S-n-butyl S'-(l, 1-dimethyl-2-hydroxyethyl) benzyl N-3-pyridyldithiocarbonimidate [MR], A, B, C and D. These metabolites were also found in the bile. The pyridine-labeled S-1358 gave rise to 2-(3'-pyridylimino)-4-carboxylthiazolidine [HM] and 3-aminopyridine [AP] in the urine, and MR and AP in the feces. Intact S-1358 was a major component of the fecal radioactivity.
