Identification of mebeverine acid as the main circulating metabolite of mebeverine in man.
The intestinal spasmolytic drug mebeverine is known to undergo fast in vivo enzymatic hydrolysis into mebeverine alcohol and veratric acid. A reversed-phase HPLC method with coulometric detection was developed in order to assay the hitherto unidentified secondary metabolite mebeverine acid. After intake of a single oral dose of 405 mg mebeverine hydrochloride in four healthy human volunteers, peak plasma concentrations of mebeverine acid were found to be 1000-fold higher than those of mebeverine alcohol, i.e. approximately 3 microg/ml versus 3 ng/ml. The appearance of mebeverine acid in plasma (median T(max)=1.25 h) as well as its disappearance (median apparent t(1/2)=1.1 h) were rapid. The urinary excretion of mebeverine acid within the first 4 h after dosing amounted to 67% of the mebeverine dose (median range: 23-107%). Mebeverine acid appears to be a valuable marker of oral exposure to mebeverine.
Stockis
Arnel
A
SGS Biopharma S.A., 1301 Bierges, Belgium. arnel.stockis@ucb-group.com
Guelen
P J M
PJ
de Vos
D
D
D000284:Administration, Oral; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D008297:Male; D010627:Phenethylamines / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine
D000927:Anticonvulsants; D010627:Phenethylamines; C076513:mebeverine alcohol; C005096:mebeverine