Comparative metabolic studies of phenacetin and structurally-related compounds in the rat.

1. A comparative study of the metabolism of [acetyl-14C]phenacetin, [acetyl-14C]methacetin, [acetyl-14C]paracetamol and [acetyl=14C]acetanilide in the rat is reported. 2. The extent of N-deacetylation, evidenced by the measurement of respired 14CO2, varied, being greatest with acetanilide (25-31%) and least with paracetamol (6%). 3. The major urinary metabolites in each case were N-acetyl-p-aminophenyl sulphate and N-acetyl-p-aminophenyl glucuronide; the relative proportions varied with the sex of the animals and as a result of extended dosage. 4. The metabolism of [ethyl-14C]phenacetin and [ethyl-14C]phenetidine was investigated and the extent of O-dealkylation determined by measurement of respired 14CO2. 5. The metabolic pathways of some related glycolanilides and oxanilic acids included N-deacylation, and in the glycolanilides, oxidation of the glycollic group.