RT Journal Article SR Electronic T1 NADPH-dependent, regioselective S-oxidation of a thionosulfur- and thioether-containing xenobiotic, diethyldithiocarbamate methyl ester by rat liver microsomes. JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 324 OP 330 VO 22 IS 2 A1 A Madan A1 M D Faiman YR 1994 UL http://dmd.aspetjournals.org/content/22/2/324.abstract AB The present study describes the NADPH-dependent, regioselective oxidation of diethyldithiocarbamate methyl ester (DDTC-Me), a dithiocarbamate ester containing both a thionosulfur (C = S) and a thioether (S-CH3) group, to two novel S-oxidized metabolites. DDTC-Me is a key metabolite in the overall bioactivation pathway for the clinically used alcohol deterrent, disulfiram. Incubation of DDTC-Me with rat liver microsomes resulted in the formation of two major metabolites. These metabolites were identified as DDTC-Me sulfoxide [S(O)CH3] and DDTC-Me sulfine (C = S+-O-) based on their NMR spectra and by MS. The formation of DDTC-Me sulfoxide was completely inhibited by the cytochrome P-450 inhibitors, emulgen 911 and 1-benzylimidazole, but only partially inhibited by heat inactivation of the flavin-containing moonooxygenases (FMO). This suggested that DDTC-Me sulfoxide formation is primarily catalyzed by cytochrome P-450 with a minor contribution from FMO. In contrast, the formation of DDTC-Me sulfine was inhibited from 60 to 80% in the presence of emulgen 911 and 1-benzylimidazole and 30 to 50% by heat inactivation of FMO, suggesting a partial role of FMO in the formation of DDTC-Me sulfine. DDTC-Me sulfoxide is a new class of dithiocarbamates that has not been previously described, whereas, DDTC-Me sulfine belongs to a class of thionosulfur sulfines that have been implicated in a number of toxicological processes.