Comparative Metabolic Studies of Phenacetin and Structurally-related Compounds in the Rat

Abstract

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.