The metabolism of 14C-oxcarbazepine in man.
The disposition of the new anti-epileptic agent oxcarbazepine (10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide) has been studied in two healthy volunteers following an oral 400 mg dose of 14C-labelled drug. The dose was excreted almost completely in the urine (94.6 and 97.1%) within six days. Faecal excretion amounted to 4.3 and 1.9% of the dose in the two subjects. In the 0-6 days urine samples the biotransformation products have been isolated and identified. 10,11-Dihydro-10-hydroxycarbamazepine (GP 47,779) and its two diastereoisomeric O-glucuronides were found as main metabolites. Taken together, they accounted for 79% of urinary 14C. Unchanged oxcarbazepine, and its sulphate and glucuronide conjugates were isolated in smaller amounts only (13%). Other minor metabolites were the trans- and cis-isomers of 10,11-dihydro-10,11-dihydroxy-carbamazepine (approximately 4%), and a phenolic derivative of GP 47,779 (less than 1%). The biotransformation of oxcarbazepine proceeds mainly by reduction to GP 47,779, and subsequent conjugation with glucuronic acid. Reduction is stereospecific, favouring the S-configuration of GP 47,779. Direct conjugation of oxcarbazepine, in the enol form, is a minor pathway. Oxidative reactions are unimportant.
D001711:Biotransformation; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000378:metabolism; D006801:Humans; D008297:Male; D000078330:Oxcarbazepine; D013237:Stereoisomerism; D013997:Time Factors
D002220:Carbamazepine; D000078330:Oxcarbazepine