Pharmacokinetics of levetiracetam XR 500 mg tablets

SummaryPurposeTo 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 3000 mg.MethodsTwo panels of 24 healthy subjects were enrolled. Study N01160 was a three-way crossover between IR fasted (single and repeated 500 mg b.i.d.), XR fasted (single and repeated 1000 mg o.d.) and XR with food (1000 mg single dose). Study N01260 was a three-way crossover single dose-proportionality between XR 1000, 2000 and 3000 mg.ResultsAfter single dose, levetiracetam XR and IR were bioequivalent with respect to AUC(0−t), AUC∞ and Cmax. The median tmax was delayed from 0.9 to 4 h. For the fed/fasted comparison, the confidence intervals around the Cmax and AUC ratios were within the 80–125% limits. At steady-state, the AUC24 h were also bioequivalent. In the dose-proportionality trial, the AUC and Cmax increased linearly with the dose. Levetiracetam XR was well tolerated.ConclusionsLevetiracetam XR 1000 mg o.d. is bioequivalent to levetiracetam IR 500 mg b.i.d. There is no food effect, and the absorption of XR is dose-proportional from 1000 to 3000 mg.