Steady-state pharmacokinetics and bioavailability of immediate-release and extended-release formulations of lamotrigine in elderly epilepsy patients: Use of stable isotope methodology

A classic 2-period crossover bioavailability study was conducted to evaluate the relative and absolute bioavailability of immediate-release (IR) and extended-release (XR) lamotrigine formulations under steady-state conditions in elderly patients with epilepsy. On treatment days, each subject's morning dose (IR or XR lamotrigine) was replaced with an intravenous 50-mg dose of stable-labeled lamotrigine. Lamotrigine concentrations were measured at 13 points between 0 and 96 hours. XR and IR lamotrigine formulations were similar with respect to steady-state area under the concentration-time curve from 0 to 24 hours (AUC_{0-24h ss}), average concentration (C_{avg, ss}), and trough concentration (C_{τ, ss}). A 33% lower fluctuation in concentrations with XR was observed relative to IR lamotrigine. The time to peak concentration (T_{max, ss}) was delayed for XR lamotrigine (3.0 vs 1.3 hours) with lower peak concentration (15% lower). The absolute bioavailability for IR and XR formulations was 73% and 92%, respectively. The formulations were bioequivalent with respect to AUC_{0-24h ss}, C_{τ, ss}, and C_{avg, ss} indicating that it may be possible to switch directly from IR to XR lamotrigine without changes in the total daily dose.