Biotransformation of 3-(2′,4′,5′-Triethoxybenzoyl)propionic Acid, a New Biliary Smooth Muscle Relaxant with Choleretic Activity, in Rats

Abstract

1. By the combined use of deuterium labelling and gas chromatographic-mass spectrometric analysis, the metabolite pattern of 3-(2′,4′,5′-triethoxybenzoy!)propionic, acid (triethoxybenzoylpropionic acid), a new biliary smooth muscle relaxant with choleretic activity, has been determined in the rat.

2. The metabolites excreted in urine and/or bile were isolated and characterized as follows: the parent drug, 3-(2′,5′-diethoxy-4′-hydroxybenzoyl)propionic acid (metabolite II), 3-(2′-ethoxy-4′-hydroxy-5′-methoxybenzoyl)propionic acid or 3-(2′-ethoxy-5′-hydroxy-4′-methoxybenzoyl)propionic acid (III), 3-(2′,4′-diethoxy-5′-hydroxybenzoyl)propionic acid (V) and 3-[2′,4′-diethoxy-5′-(2-hydroxyethoxy)benzoyl]propionic acid (VI).

3. The primary route of biotransformation of triethoxybenzoylpropionic acid in the rat was either O-de-ethylation at the C-4′ and C-5′ positions or β-hydroxylation of the ethoxy group at the C-5′ position in the parent molecule.

4. All these excreted products except metabolite VI were eliminated both unconjugated and in conjugates (probably glucuronides and/or sulphates).

5. The rat excreted mainly metabolites V and VI in the urine and parent drug, metabolites V and VI in the bile.