Human Urinary Metabolites of 3-(2′,4′,5′-Triethoxybenzoyl)propionic Acid, a New Biliary Smooth Muscle Relaxant with Choleretic Activity

Abstract

1. Biotransformation of 3-(2′,4′,5′-triethoxybenzoyl)propionic acid (tri-, ethoxybenzoylpropionate) was studied in man using isotopic cluster technique. From the 24 h urine of a male volunteer given an equimolar mixture of non-labelled and pentadeuterium-labelled triethoxybenzoylpropionate (1 mg/kg) orally, the parent drug, 3-(2′,5′-diethoxy-4′-hydroxybenzoyl)propionic acid (4′ -phenol) and 3-(2′,4′-diethoxy-5 ‘-hydroxybenzoyl)propionic acid (5′-phenol) were isolated and identified by g.I.c.-mass spectrometry.

2. Urinary components were also quantified by mass chromatography: the parent drug (67·4% of dose) and 4′- and 5 ‘-phenols in a mixture (20·3%). More than 80% of urinary triethoxybenzoylpropionate was present as its glucuronic acid ester, as evidenced by using β-glucuronidase and saccharo-1,4-lactone, a specific inhibitor of the enzyme. Almost all of 4′- and 5′-phenols appeared as conjugates with glucuronic acid and/or sulphuric acid. These findings indicated that in man triethoxybenzoylpropionate was largely conjugated with glucuronic acid and in part underwent deethylation followed by conjugation for elimination mainly in urine.