Influence of disulfiram, diethyldithiocarbamate and carbon disulfide on the metabolic formation of trifluoroacetic acid from halothane in the rat.
Halothane (H), 2-bromo-2-chloro-1,1,1-trifluoroethane, was metabolized to trifluoroacetic acid (TFAA) over a very long time (several days) in rats after a 1 h exposure to the inhalational anesthetic. H inhibited its own metabolism as long as anesthetically active concentrations existed in the serum and tissue. That fraction of H which was not exhaled rapidly by the lung after the anesthesia was metabolized mainly over the time range from 5-48 h: 68% of the total amount of TFAA eliminated in the urine during 144 h (about 4 mg) were found in this time period. Disulfiram (D) dose dependently inhibited the formation of TFAA from H in vivo and in vitro, in liver microsomes of phenobarbital treated rats. Diethyldithiocarbamate (DDTC) and carbon disulfide (CS2), two metabolites of D, given to rats immediately after the H-anesthesia also reduced the metabolic formation of TFAA. However, if DDTC and CS2 were given 24 h before the anesthesia they caused only a small decrease in serum TFAA concentration. This finding indicates that both metabolites of D have only short-lasting inhibitory effects. In contrast, the inhibition of the oxidative metabolism of H by D seems to persist over a long time, since a small but significant decrease in the serum TFAA concentration was found even if D was given 72 h before the H-anesthesia. It was concluded that in vivo CS2 is really the active inhibitor. The short-lasting inhibitory effect of DDTC may be explained by its fast metabolic transformation into CS2, whereas the long-lasting effect of D is caused by its delayed degradation into this metabolite.
D000769:Anesthesia, Inhalation; D000818:Animals; D002246:Carbon Disulfide / Q000494:pharmacology*; D004221:Disulfiram / Q000494:pharmacology*; D004050:Ditiocarb / Q000494:pharmacology*; D005463:Fluoroacetates / Q000378:metabolism*; D006221:Halothane / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013859:Thiocarbamates / Q000494:pharmacology*; D014269:Trifluoroacetic Acid / Q000097:blood / Q000378:metabolism* / Q000652:urine
D005463:Fluoroacetates; D013859:Thiocarbamates; D004050:Ditiocarb; D014269:Trifluoroacetic Acid; D002246:Carbon Disulfide; D004221:Disulfiram; D006221:Halothane