Hepatic disposition and biliary excretion of the organic cations thiazinamium and thiazinamium sulfoxide in rats.
The disappearance from plasma and the excretion in bile of the monoquaternary thiazinamium (administered as the iodide) and one of its polar metabolites, thiazinamium sulfoxide (also administered as the iodide), were studied in the rat after intravenous injection to obtain more information on hepatic transport mechanisms for organic cations. Both compounds exhibited an extremely rapid plasma disappearance, partly due to a rapid liver uptake. After injection of thiazinamium iodide and thiazinamium sulfoxide iodide, 36 and 47%, respectively, of the administered dose were excreted in bile during 1 hr. TLC analysis of the bile showed at least two unidentified polar metabolites in addition to thiazinamium sulfoxide and only 3.8% unchanged thiazinamium after administration of thiazinamium iodide. The same metabolites were found after injection of thiazinamium sulfoxide iodide. Urinary excretion and intestinal secretion were 18 and 12%, respectively, for thiazinamium sulfoxide iodide and 27 and 9%, respectively, of the dose for thiazinamium iodide. It is concluded that, in spite of unequal physicochemical features, thiazinamium iodide and thiazinamium sulfoxide iodide differ only slightly in hepatic uptake and metabolism.
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001711:Biotransformation; D001798:Blood Proteins / Q000378:metabolism; D002855:Chromatography, Thin Layer; D066298:In Vitro Techniques; D008055:Lipids; D008099:Liver / Q000378:metabolism*; D008297:Male; D011398:Promethazine / Q000031:analogs & derivatives* / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D012995:Solubility; D013454:Sulfoxides / Q000378:metabolism
D001798:Blood Proteins; D008055:Lipids; D013454:Sulfoxides; C013708:thiazinamium sulfoxide; D011398:Promethazine