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National Institute of Environmental Health Sciences

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Publication Detail

Title: Metabolism of [14C]- and [35S]S-(1,2-dichlorovinyl)-L-cysteine in the male Fischer 344 rat.

Authors: Finkelstein, M B; Patel, N J; Anders, M W

Published In Drug Metab Dispos, (1995 Jan)

Abstract: The metabolic fate, tissue distribution, and elimination profile of [35S]- and [cysteine-U-14C]S-(1,2-dichlorovinyl)-L-cysteine (DCVC)--given either intravenously or intraperitoneally to male Fischer 344 rats--was investigated. Blood samples were collected periodically from 5 min to 96 hr after administration. More than 99% of the DCVC was cleared from plasma within 2.5 hr after either intravenous or intraperitoneal injection. The initial half-lives of both [35S]- and [14C]DCVC were 2.0 and 2.8 hr, respectively, and the mercapturate S-(1,2-dichlorovinyl)-N-acetyl-L-cysteine was detected in plasma within 5 min of giving DCVC. The major plasma metabolite detected after giving [35S]DCVC was inorganic sulfate, and S-(1,2-dichlorovinyl)-N-acetyl-L-cysteine and pyruvate were also detected in plasma after giving [14C]DCVC. S-(1,2-Dichlorovinyl)-N-acetyl-L-cysteine was the major urinary metabolite detected after giving [14C]DCVC, and inorganic sulfate was excreted in the urine after giving [35S]DCVC. Administration of the cysteine conjugate beta-lyase inhibitor aminooxyacetic acid led to a significant increase in the urinary excretion of radioactivity, mostly in the form of the mercapturate. The kidney contained the highest amount of radioactivity after administration of [35S]DCVC. In addition, similar amounts of radioactivity were present in brain, heart, kidney, and liver after administration of [14C]DCVC, but the 14C content of the liver was decreased in aminooxyacetic acid-treated rats. This study shows that DCVC is rapidly metabolized to inorganic sulfate and S-(1,2-dichlorovinyl)-N-acetyl-L-cysteine, which are eliminated in the urine.

PubMed ID: 7720515 Exiting the NIEHS site

MeSH Terms: Aminooxyacetic Acid/pharmacology; Animals; Biotransformation; Chromatography, High Pressure Liquid; Cysteine/administration & dosage; Cysteine/analogs & derivatives*; Cysteine/blood; Cysteine/pharmacokinetics; Half-Life; Injections, Intraperitoneal; Injections, Intravenous; Male; Rats; Rats, Inbred F344; Research Support, U.S. Gov't, P.H.S.; Sulfates/metabolism; Tissue Distribution

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