Abstracts

RATIONALE: Use of levetiracetam (LEV) as add-on treatment requires an understanding of potential kinetic interactions with concomitant AEDs. This evaluation was performed to assess potential pharmacokinetic interactions between LEV and frequently co-administered AEDs including CBZ, PHT, VPA, PB, LTG and GBP. METHODS: A meta-analysis was performed analyzing the serum concentrations of AEDs in randomized, placebo controlled phase III trials when LEV was added to a steady-state drug regimen in patients with epilepsy. The 90% confidence intervals and ratios of geometric means of AEDs were determined at stable doses between baseline and treatment phase with LEV at doses of 1000, 2000, 3000 or 4000 mg/day, and compared using repeated measures model, serum levels of various AEDs. The 80-125% boundaries were used to demonstrate lack of interaction. LEV serum concentrations were analyzed for pharmacokinetic variables including half-life (T1/2), serum concentrations at one and 12 hours (C1h, C12h), and area under curve (AUC). RESULTS:_ Serum levels of LEV and AEDs were evaluated in 672 patients randomized to LEV and 351 randomized to placebo. Ratios (CI) following LEV or Placebo, respectively were CBZ 0.963-0.993/0.969-1.010 (n= 368, 212), PHT 0.942-1.041; 0.831-0.947 (n= 109, 65), LTG 0.922-1.039; 0.956-1.129 (n= 48, 25), GBP 0.914-1.049; 0.882-1.105 (n= 57, 22), PB 0.962-1.069; 0.997-1.136 (n= 44, 30), and VPA 0.909-0.974; 0.925-1.025 (n= 118, 56). Based on the established boundaries, LEV did not increase or decrease steady-state serum concentrations of concomitant AEDs. In addition LEV C1h and AUC were comparable to those observed in non-comedicated subjects. CONCLUSIONS: This meta-analysis demonstrates that LEV does not affect the steady state serum concentration of other AEDs, nor do other AEDs affect LEV pharmacokinetics. This lack of interaction is advantageous when LEV is selected for adjunctive treatment.