Urinary metabolites of benzbromarone in man

Benzbromarone [3,5-dibromo-4-hydroxyphenyl)-(2-ethyl-3-benzofuranyl)-ketone) is a widely used uricosuric drug which was reported to be metabolized by successive debromination. Recently, however, it was reported that benzbromarone is not debrominated but hydroxylated at the ethyl side chain. The presented paper describes further studies on the metabolism of the drug in man. The metabolites were identified in urine samples from two different patients intoxicated suicidally with high doses of benzbromarone after cleavage of conjugates, extraction and derivatization by acetylation using gas chromatography-mass spectrometry. The following five metabolites could be identified besides the unchanged benzbromarone (BB): hydroxy-alkyl-BB, oxo-BB, two isomers of hydroxyaryl-BB and hydroxy-methoxy-aryl-BB. Therefore, the following two phase I metabolic pathways can be postulated: successive oxidation of the ethyl side chain and one- and twofold hydroxylation of the benzofuran ring followed by methylation of one of the hydroxy groups. Benzbromarone and its metabolites are excreted in urine partly in a conjugated form. Debrominated metabolites could not be detected, although the concentrations of benzbromarone and its metabolites were very high in the urine samples studied.