The metabolism of thioacetanilide in the rat.
The metabolism and acute toxicity of thioacetanilide was studied in the rat. Following intragastric dosage (100 mg/kg), over 90% dose was excreted in urine, predominantly as conjugated metabolites: less than 7% was recovered in the faeces, consisting of unchanged thioacetanilide. N-Acetyl-4-aminophenol sulphate was the major urinary metabolite, with smaller amounts of conjugated 4-hydroxythioacetanilide and unmetabolized thioacetanilide. Biliary excretion amounted to only 3.4% and was N-acetyl-4-aminophenol glucuronide. Although desulphuration was a major metabolic pathway in the rat, no hepatic toxicity (shown by serum enzymes, plasma bilirubin, hepatic glutathione and cytochrome P-450 levels) occurred up to doses of 500 mg/kg. Combination of rapid 4-hydroxylation, absence of sulphoxide formation, and the structural tautomerism exhibited by thioacetanilide may be, in part, responsible for these findings.
D000083:Acetanilides / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000187:drug effects; D001663:Bilirubin / Q000378:metabolism; D005243:Feces / Q000032:analysis; D005978:Glutathione / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000083:Acetanilides; D005978:Glutathione; C039632:thioacetanilide; D001663:Bilirubin