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.

摘要

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 (100-400 mg/day) for >or=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 mg/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 (AUCtau) 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 >or=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 lamotrigine is required and the combination was generally safe and well tolerated.