title: Effect of diethyldithiocarbamate on the metabolic elimination of hexobarbital, phenazone, tolbutamide and four halogenated hydrocarbons.
abstract: The present study describes the inhibitory effects of diethyldithiocarbamate (dithiocarb) on the metabolic elimination of hexobarbital, phenazone, tolbutamide and four halogenated hydrocarbons. The plasma half-life for the beta-slopes of hexobarbital (25 mg/kg, i.v.) and phenazone (50 mg/kg, i.v.) were increased 2.5 and 3.5 fold respectively, when dithiocarb (100 mg/kg, i.p.) was administered simultaneously. The plasma half-life of tolbutamide was 2.27 h, when administered alone to rats; and 4.04 h, when administered with dithiocarb. Metabolic elimination of halothane, trichloroethylene, dichloroethane, and carbon tetrachloride, from the atmosphere of a closed exposure system was studied in rats. Treatment with dithiocarb (100 mg/kg, i.p.) immediately before exposure, prolonged the elimination half-life of: halothane (103 parts/10(6)) by a factor of 7.6, of trichloroethylene (25 parts/10(6)) by a factor of 5.3; dichloroethane (69 parts/10(6)) by 4.6; and carbon tetrachloride (38 parts/10(6)) by 2.4, respectively. The inhibitory actions of dithiocarb on the metabolism of the tested drugs and chemicals are explained as the consequences of a depressed microsomal mono-oxygenase activity due to a decrease in the cytochrome P 450 content.
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000378:metabolism*; D004050:Ditiocarb / Q000494:pharmacology*; D006591:Hexobarbital / Q000494:pharmacology*; D006846:Hydrocarbons, Halogenated / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology*; D014044:Tolbutamide / Q000378:metabolism*
chemical_list: D006846:Hydrocarbons, Halogenated; D013859:Thiocarbamates; D014044:Tolbutamide; D004050:Ditiocarb; D006591:Hexobarbital; D006899:Mixed Function Oxygenases; D000983:Antipyrine