The effect of felbamate on valproic acid disposition

Mary L. Wagner, Nina M. Graves, Ilo E. Leppik, Rory P. Remmel, Robert C. Shumaker, Donna L. Ward, James L. Perhach

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Felbamate is a new antiepileptic drug approved for partial and secondarily generalized seizures. 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. 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. 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:

Original languageEnglish (US)
Pages (from-to)494-502
Number of pages9
JournalClinical Pharmacology & Therapeutics
Volume56
Issue number5
DOIs
StatePublished - Nov 1994

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    Wagner, M. L., Graves, N. M., Leppik, I. E., Remmel, R. P., Shumaker, R. C., Ward, D. L., & Perhach, J. L. (1994). The effect of felbamate on valproic acid disposition. Clinical Pharmacology & Therapeutics, 56(5), 494-502. https://doi.org/10.1038/clpt.1994.170