Effect of felbamate on the pharmacokinetics of lamotrigine.
To assess the possible interaction between lamotrigine and felbamate, a double-blind, randomized, placebo-controlled, two-way crossover study was conducted in 21 healthy male volunteers. Volunteers were given lamotrigine (100 mg every 12 hours) and felbamate (1,200 mg every 12 hours) or matching placebo for 10 days during each period of the crossover. After morning administration on day 10, blood samples were obtained over 12 hours for measurement of lamotrigine. Felbamate increased the maximum concentration (Cmax) and and area under the concentration-time curve from time 0 to 12 hours (AUC0-12) of lamotrigine by 13% and 14%, respectively, compared with placebo. The 90% confidence intervals of the log-transformed pharmacokinetic parameters were within the 80-125% bioequivalance limits, however. Felbamate had no significant effect on the urinary excretion of lamotrigine (total), unconjugated lamotrigine, or the N-glucuronide. One volunteer discontinued the study after developing a rash while taking lamotrigine and placebo. All other adverse events were primarily related to the central nervous system and gastrointestinal tract, with a higher incidence reported during coadministration of lamotrigine and felbamate than with placebo. Overall, felbamate appears to have no clinically relevant effects on the pharmacokinetics of lamotrigine.
Colucci
R
R
Department of Clinical Pharmacology, Schering-Plough Research Institute, Kenilworth, New Jersey, USA.
Glue
P
P
Holt
B
B
Banfield
C
C
Reidenberg
P
P
Meehan
J W
JW
Pai
S
S
Nomeir
A
A
Lim
J
J
Lin
C C
CC
Affrime
M B
MB
D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000078328:Felbamate; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology*; D013810:Therapeutic Equivalency; D014227:Triazines / Q000097:blood / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D014227:Triazines; D000077213:Lamotrigine; D000078328:Felbamate