METABOLISM OF BECLAMIDE AFTER A SINGLE ORAL DOSE IN MAN - QUANTITATIVE STUDIES

A simple reverse phase HPLC assay is described for the determination o f the anticonvulsant compound, beclamide and its 3- and 4-hydroxypheny l metabolites in urine. Following oral administration of 1 g beclamide to a panel of healthy volunteers, less than 0.4% of the dose was excr eted unchanged in the 24-h urine and unconjugated 3- and 4-hydroxyphen yl metabolites were not detected. Based on examination of the urine af ter incubation with beta-glucuronidase and aryl sulphatase, it was fou nd that these hydroxyl metabolites were excreted as both glucuronide a nd sulphate conjugates. For each metabolite the glucuronide was the ma jor excretory product (approximately 10:1). The 24-h excretion of the combined conjugated metabolites was 7% (for the 3-hydroxy metabolite) and 24% (for the 4-hydroxy metabolite) of the dose. Approximately 22% of the administered dose of beclamide was excreted as hippuric acid. I n view of the simplicity of assay, beclamide may be a useful tool subs tance with which to examine factors influencing the xenobiotic metabol ic pathways of benzene ring hydroxylation and glucuronide and sulphate conjugation in man.