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The effect of felbamate on valproic acid disposition
Author(s) -
Wagner Mary L,
Graves Nina M,
Leppik Ilo E,
Remmel Rory P,
Shumaker Robert C,
Ward Donna L,
Perhach James L
Publication year - 1994
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 - 10.1038/clpt.1994.170
Subject(s) - felbamate , valproic acid , anticonvulsant , chemistry , pharmacology , pharmacokinetics , crossover study , epilepsy , medicine , alternative medicine , pathology , psychiatry , placebo
Felbamate is a new antiepileptic drug approved for partial and secondarily generalized seizures. Design Subjects with epilepsy (three men and seven women; age range, 20 to 39 years; weight range, 53 to 88 kg) who were previously stabilized with valproic acid, 9.5 to 31.7 mg/kg/day, received both 600 and 1200 mg felbamate twice a day in an open‐label, randomized, crossover study. Results Coadministration of 1200 or 2400 mg felbamate increased the mean valproic acid area under the curve (from 802.2 to 1025.4 and 1235.9 mg/hr/ml, respectively), peak concentrations (from 86.1 to 115.1 and 133.4 mg/ml, respectively), and average steady‐state concentrations (from 66.9 to 85.5 and 103.0 mg/ml, respectively). No changes were observed in valproic acid time to peak concentration or protein binding. Average steady‐state felbamate concentrations were 34.7 mg/ml for 600 mg administered twice daily and 61.2 mg/ml for 1200 mg administered twice daily. Conclusion When felbamate is added to a regimen of valproic acid, valproic acid doses may require reduction because coadministration of felbamate decreased steady‐state vaiproic acid clearance (28% and 54%, respectively; p < 0.01). Clinical Pharmacology and Therapeutics (1994) 56, 494–502; doi: 10.1038/clpt.1994.170