Identification of a dithiol intermediate metabolite of malotilate in rats.
1. A chemically unstable dithiol intermediate metabolite of malotilate was identified by g.l.c.-mass spectrometry after conversion of the dithiol to a stable derivative by a cyclization reaction with 1,3-dichloroacetone. The dithiol, namely, 2,2-di(isopropoxycarbonyl)ethylene-1,1-dithiol, was present in rat liver at low concentrations. 2. A study of glucuronidation in vitro indicated that the dithiol was converted to the corresponding thio-glucuronide by rat hepatic microsomal enzymes. 3. It was thus confirmed that metabolism of malotilate proceeds via the dithiol intermediate to form the thio-glucuronide, which is a major metabolic pathway.
Nakaoka
M
M
Research Institute, Daiichi Seiyaku Co., Ltd., Tokyo, Japan.
Suzuki
W
W
Hakusui
H
H
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry; D005965:Glucuronates / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D008314:Malonates / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014050:Toluene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D015262:Xenobiotics
D005965:Glucuronates; D008314:Malonates; D015262:Xenobiotics; D014050:Toluene; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate; C004848:dithiol