Metabolism and pharmacokinetics of S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine in rats.

B H Lee, Y S Song, J Park, J C Ryu
Author Information
  1. B H Lee: Doping Control Center, Korea Institute of Science and Technology, Seoul, Korea.

Abstract

The metabolism and pharmacokinetics of a mixed disulfide S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine (AC-DDTC) were studied in rats. Two metabolites of AC-DDTC following i.v. and p.o. administration were identified in plasma and liver by HPLC and GC, namely N,N-diethyldithiocarbamate (DDTC) and the methyl ester of DDTC (Me-DDTC). AC-DDTC was very unstable in vivo and could not be detected neither in plasma nor in urine. Pharmacokinetic parameters of DDTC following intravenous administration of AC-DDTC (20 mg/kg) were calculated. DDTC has a low affinity to rat tissue and the total body clearance was 9.0 +/- 3.4 ml/min/kg. The mean residence time (MRT) was 111.5 +/- 16.3 min. After oral administration of 20 mg/kg AC-DDTC, maximal plasma concentration (Cmax) was 3.8 +/- 0.2 nmol/ml and the bioavailability was 7.04%. Cmax for DDTC at a dose of 120 mg/kg AC-DDTC was 40.1 +/- 2.2 nmol/ml. MRT was 47.1 +/- 2.8 min at a dose of 20 mg/kg and 110.5 +/- 6.0 min at 120 mg/kg.

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MeSH Term

Acetylcysteine
Animals
Antimutagenic Agents
Area Under Curve
Chromatography, High Pressure Liquid
Indicators and Reagents
Male
Rats
Rats, Sprague-Dawley

Chemicals

Antimutagenic Agents
Indicators and Reagents
S-(N,N-diethyldithiocarbamoyl)-N-acetylcysteine
Acetylcysteine

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