Pharmacokinetics of levetiracetam XR 500 mg tablets

摘要

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 3000 mg.Methods: Two 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.Results: After single dose, levetiracetam XR and IR were bioequivalent with respect to AUC_(0_t), AUC and C_maxThe 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 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.