Formation of reactive metabolites of phenacetin in humans and rats.
The metabolism of phenacetin to reactive intermediates in humans was estimated from the excretion of thio adducts in urine. N-Hydroxyphenacetin, a precursor of reactive metabolites, was also quantified. Following an oral dose of phenacetin (10 mg/kg) to humans, these metabolites in 24 h urine were: paracetamol-3-cysteine, 4.4% dose; paracetamol-3-mercapturate, 3.9%; 3-thiomethylparacetamol, 0.4%; N-hydroxyphenacetin, 0.5%. Rats showed a considerable increase in N-hydroxyphenacetin excretion after chronic dosing with phenacetin at high dosage (500 mg/kg) for one month. chronic dosing with a low dose (50 mg/kg) did not increase N-hydroxyphenacetin excretion, but a marked increase occurred on concomitant administration of aspirin and caffeine.
D000328:Adult; D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D010615:Phenacetin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D051381:Rats
C008068:N-hydroxyphenacetin; D010615:Phenacetin