Studies in detoxication. 22. The metabolism of phenacetin (p-ethoxyacetanilide) in the rabbit and a further observation on acetanilide metabolism

Abstract

Phenacetin was largely transformed in the rabbit into p-acetamido-phenylglucuronide and p-acetamidophenylsulfuric acid, these occurring in the urine in the ratio 6.9:1. The major metabolic change undergone by phenacetin was deethylation followed by conjugation. Deacetylation of phenacetin occurred only to a very minor extent as shown by the detection of traces of free p-phenet-idine in the urine, and the isolation of minute amts. of a crystalline complex of p-toluidine and ammonium glucuronate derived from a labile glucuronide which is a major metabolite of p-phenetidine in the rabbit. Acetanilide was also slightly deacetyla-ted, for acetanilide urine also contained traces of a labile glucuronide which is a major metabolite of aniline.