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 stud y was conducted in 21 healthy male volunteers. Volunteers were given l amotrigine (100 mg every 12 hours) and felbamate (1,200 mg every 12 ho urs) or matching placebo for 10 days during each period of the crossov er. After morning administration on day 10, blood samples were obtaine d over 12 hours for measurement of lamotrigine. Felbamate increased th e maximum concentration (C-max) and and area under the concentration-t ime curve from time 9 to 12 hours (AUC(0-12)) of lamotrigine by 13% an d 14%, respectively, compared with placebo. The 90% confidence interva ls of the log-transformed pharmacokinetic parameters were within the 8 0-125% bioequivalence limits, however. Felbamate had no significant ef fect on the urinary excretion of lamotrigine (total), unconjugated lam otrigine, or the N-glucuronide. One volunteer discontinued the study a fter developing a rash while taking lamotrigine and placebo. All other adverse events were primarily related to the central nervous system a nd gastrointestinal tract, with a higher incidence reported during coa dministration of lamotrigine and felbamate than with placebo. Overall, felbamate appears to have no clinically relevant effects on the pharm acokinetics of lamotrigine.