title: Variable inhibition of human hepatic drug metabolizing enzymes by disulfiram.
abstract: In healthy adult males, oral treatment with disulfiram exerted variable inhibitory effects on various metabolic parameters of the hepatic microsomal enzyme system: Two 10 mg/kg doses, given at an interval of 24 hr produced only a marginally significant prolongation of the plasma elimination half-life of antipyrine. This effect was not detectable when using as a criterion the formation of 4-OH-antipyrine (aromatic C-hydroxylation), as measured by its renal excretion. In contrast, a single dose of disulfiram (10 mg/kg) was followed by a significant decrease in the formation of D-glucaric acid, which was demonstrable for 6 days and was measured by the renal excretion of D-glucaric acid over 24-hr periods. The same single dose of disulfiram (10 mg/kg) did not affect the activity of the serum gamma-glutamyl transpeptidase. However, a single dose as small as 5 mg/kg caused a temporary but significant reduction in the formation of 4-aminoantipyrine from aminophenazone (oxidative demethylation), where the renal excretion of 4-aminoantipyrine provided a measure of the decrease. During the subsequent phase of excretion, the deficit in 4-aminoantipyrine elimination was completely compensated for. It is concluded from the results that in man the impairment of oxidative N-demethylation constitutes the most sensitive criterion of a measurable inhibitory effect of disulfiram on the hepatic mixed-function oxygenase system.
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000632:Aminopyrine / Q000097:blood; D000983:Antipyrine / Q000097:blood; D004221:Disulfiram / Q000494:pharmacology*; D005937:Glucaric Acid / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D013997:Time Factors
chemical_list: D000632:Aminopyrine; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D000410:Alanine Transaminase; D005937:Glucaric Acid; D000983:Antipyrine; D004221:Disulfiram