Effect of diethyldithiocarbamate on the metabolic elimination of hexobarbital, phenazone, tolbutamide and four halogenated hydrocarbons.
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.
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*
D006846:Hydrocarbons, Halogenated; D013859:Thiocarbamates; D014044:Tolbutamide; D004050:Ditiocarb; D006591:Hexobarbital; D006899:Mixed Function Oxygenases; D000983:Antipyrine