The metabolism of thioacetanilide in the rat

Abstract

1. The metabolism and acute toxicity of thioacetanilide was studied in the rat. Following intragastric dosage (100mg/kg), over 90% dose was excreted in urine, predomi-nantly as conjugated metabolites: less than 7% was recovered in the faeces, consisting of unchanged thioacetanilide.

2. 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.

3. 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 500mg/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.