Pharmacokinetics of levetiracetam XR 500mg tablets.

PURPOSE

To compare the relative bioavailability of levetiracetam extended-release tablets (XR) with immediate release tablets (IR) following single and multiple dosing; to assess the food effect and the dose-proportionality of XR from 1000 to 3000mg.

METHODS

Two panels of 24 healthy subjects were enrolled. Study N01160 was a three-way crossover between IR fasted (single and repeated 500mg b.i.d.), XR fasted (single and repeated 1000mg o.d.) and XR with food (1000mg single dose). Study N01260 was a three-way crossover single dose-proportionality between XR 1000, 2000 and 3000mg.

RESULTS

After single dose, levetiracetam XR and IR were bioequivalent with respect to AUC((0-t)), AUC(infinity) and C(max). The median t(max) was delayed from 0.9 to 4h. For the fed/fasted comparison, the confidence intervals around the C(max) and AUC ratios were within the 80-125% limits. At steady-state, the AUC(24h) were also bioequivalent. In the dose-proportionality trial, the AUC and C(max) increased linearly with the dose. Levetiracetam XR was well tolerated.

CONCLUSIONS

Levetiracetam XR 1000mg o.d. is bioequivalent to levetiracetam IR 500mg b.i.d. There is no food effect, and the absorption of XR is dose-proportional from 1000 to 3000mg.