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

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 iv and po 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 (C(max) was 3.8 ± 0.2 nmol/ml and the bioavailability was 7.04%. C(max) for DDTC at a dose of 120 mg/kg. AC-DDTC wa 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.