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Effects of felbamate on the pharmacokinetics of the monohydroxy and dihydroxy metabolites of oxcarbazepine
Author(s) -
Hulsman Jacques A.R.J.,
Rentmeester Theo W.,
Banfield Christopher R.,
Reidenberg Pascale,
Colucci Robert D.,
Meehan Jeffrey W.,
Radwanski Elaine,
Mojaverian Parviz,
Lin ChinChung,
Nezamis James,
Affrime Melton B.,
Glue Paul
Publication year - 1995
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/0009-9236(95)90050-0
Subject(s) - felbamate , oxcarbazepine , pharmacokinetics , anticonvulsant , crossover study , pharmacology , placebo , urine , chemistry , medicine , epilepsy , carbamazepine , alternative medicine , pathology , psychiatry
The effects of felbamate on the multiple dose pharmacokinetics of the monohydroxy and dihydroxy metabolites of oxcarbazepine were assessed in a placebo‐controlled, randomized, double‐blind crossover study in 18 healthy male volunteers. Oxcarbazepine, 1200 mg/day, was administered on an open basis in combination with double‐blind placebo or 2400 mg/day felbamate for two 10‐day treatment periods separated by a 14‐day washout period. Pharmacokinetic parameters of monohydroxyoxcarbazepine and dihydroxyoxcarbazepine were determined from plasma and urine samples obtained on the tenth day of each treatment period. Felbamate had no effect on monohydroxyoxcarbazepine plasma or urine pharmacokinetics compared with placebo, but it significantly increased values for dihydroxyoxcarbazepine maximum concentration and area under the curve from 0 to 12 hours, as well as urinary excretion of free and total dihydroxyoxcarbazepine. The mechanism that may account for the observations is the induction of oxidative metabolism of monohydroxyoxcarbazepine. Despite these changes, the relative amount of dihydroxyoxcarbazepine is small in comparison to monohydroxyoxcarbazepine, and antiepileptic activity is associated with monohydroxyoxcarbazepine rather than dihydroxyoxcarbazepine. Therefore we conclude that felbamate has no clinically relevant effects on the pharmacokinetics of oxcarbazepine in humans. Clinical Pharmacology & Therapeutics (1995) 58 , 383–389; doi: