A non-randomized study to investigate the effects of the atypical antipsychotic aripiprazole on the steady-state pharmacokinetics of lamotrigine in patients with bipolar I disorder

Objective To determine the effect of aripiprazole on steady-state pharmacokinetics of lamotrigine in patients with bipolar I disorder who were clinically stable on lamotrigine (100-400mg/day) for >= 4 weeks. Methods In this open-label study, aripiprazole was administered at 10 mg/day for 3 days, 20 mg/day for 3 days, then 30 rng/day for 8 days. Blood samples were collected on Days -1 and 14 for determination of lamotrigine steady-state pharmacokinetic parameters. Safety and tolerability were assessed. Results Eighteen patients were administered aripiprazole in combination with lamotrigine. Geometric mean (GM) values for lamotrigine maximum plasma concentration were similar for lamotrigine alone (26 ng/mL) and with co-administered aripiprazole (23 ng/mL). GM values for plasma lamotrigine area under the concentration-time curve (AUC tau) were comparable for lamotrigine alone (434 ng/h/mL) and with co-administered aripiprazole (394 ng/h/mL). Median T-max of lamotrigine alone and combined with aripiprazole was 1.98 and 0.77 h, respectively. No changes to lamotrigine dose-normalized plasma trough concentrations were observed with co-administered aripiprazole. Sixteen patients (88.9%) experienced >= 1 adverse event (AE), the most common of which was insomnia (n = 6). Conclusions Aripiprazole had no meaningful effect on lamotrigine steady-state pharmacokinetics in patients with bipolar I disorder. No dosage adjustment of larnotrigine is required and the combination was generally safe and well tolerated. Copyright (C) 2009 John Wiley & Sons, Ltd.