Factors Affecting the Metabolism of Phenacetin II. Effect of Aspirin, Caffeine, Codeine, Ethanol and Phenobarbital on the Metabolism of [acetyl-¹⁴C]-Phenacetin in the Rat

Abstract

1. The influence of several drugs, namely acetylsalicylic acid, caffeine, codeine, alcohol and phenobarbitone and various combinations of these drugs, on the metabolism and excretion of [acetyl-¹⁴C]phenacetin in the rat has been studied.

2. The metabolism and excretion of [acetyl-¹⁴C]phenacetin is not markedly influenced by any of the drugs with the exception of acetylsalicylic acid either alone or in combination with caffeine or codeine.

3. Acetylsalicylic acid impedes the sulphate conjugation of N-acetyl-p-aminophenol leading to an increase in the urinary excretion of the glucuronic acid conjugate, the cysteine conjugate and the unconjugated compound.

4. The findings are discussed in relation to the nephrotoxicity of phenacetin and acetylsalicylic acid containing analgesic combinations.