Metabolism of pheneturide in the rat and in man

The biotransformation of pheneturide was studied in humans and in the rat. Human volunteers received a single oral dose of 10 mg/kg of pheneturide and the rats were given repeated doses of 250 mg/kg. Urine from both study groups was extracted with Amberlite XAD-2 and the extracts were separated by preparative HPLC after enzymatic hydrolysis. Five metabolites were isolated in man and their structures were determined using NMR and mass spectrometry. The hydrolysis of the ureide function and the 4-hydroxylation of the benzene ring led to the formation of two major metabolites: 2-(4-hydroxyphenyl)-butyroylurea (37.5%) and 2-phenylbutyric acid (40.6%), and to one minor metabolite: 2-(4-hydroxyphenyl)-butyric acid (11.9%). Seven metabolites were isolated in the rat. The 4-hydroxylation of the benzene ring and the C 3 hydroxylation of the aliphatic chain led to the formation of two major metabolites: 2-(4-hydroxyphenyl)-butyroylurea (70.5%) and 3-hydroxy-2-phenyl-butyroylurea (19.6%), whereas the hydrolysis of the ureide function was less important. Only traces of the parent drug were found in humans as well as in the rat.