The effect of felbamate on valproic acid disposition.
BACKGROUND
Felbamate is a new antiepileptic drug approved for partial and secondarily generalized seizures.


METHODS
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.


CONCLUSIONS
When felbamate is added to a regimen of valproic acid, valproic acid doses may require reduction because coadministration of felbamate decreased steady-state valproic acid clearance (28% and 54%, respectively; p < 0.01).
Wagner
M L
ML
College of Pharmacy, University of Minnesota, Minneapolis.
Graves
N M
NM
Leppik
I E
IE
Remmel
R P
RP
Shumaker
R C
RC
Ward
D L
DL
Perhach
J L
JL
D000328:Adult; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism*; D000078328:Felbamate; D005260:Female; D006801:Humans; D008297:Male; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D011485:Protein Binding; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
D048448:Phenylcarbamates; D011409:Propylene Glycols; D014635:Valproic Acid; D000078328:Felbamate