PURPOSE: To investigate the tolerability and pharmacokinetics of oral loading with lamotrigine (LTG) among epilepsy patients after temporary drug discontinuation in an epilepsy monitoring unit. METHODS: We conducted a pilot study among epilepsy patients (18 years or older) receiving maintenance doses of LTG. LTG was discontinued on admission and restarted at the end of epilepsy monitoring. LTG was given as a single oral dose calculated based on the population expected volume of distribution (Vd, 1.0 L/kg) and target blood level on admission. Baseline and serial blood levels of LTG were determined hourly for 10 to 12 h after the loading dose. Outcome measures: (a) frequency of patients with side effects; (b) time to maximum concentration (Tmax), maximum concentration (Cmax), actual volume of distribution, and half-life. RESULTS: Twenty-four patients received a single oral load of LTG (mean, 6.5 +/- 2.7 mg/kg). Overall, LTG loading was well tolerated with no serious adverse events or skin rash observed. Two patients had transient and mild nausea 1 to 2 h after the oral load. The mean estimated pharmacokinetic parameters are as follows: Tmax, 3.1 +/- 2.1 h; Cmax, 8.2 +/- 6.5 mg/L; Vd, 1.1 +/- 1.0 L/kg; clearance, 0.08 +/- 0.08 mg/L/h; half-life, 22 +/- 30 h. All patients reached their target blood levels. CONCLUSIONS: Epilepsy patients temporarily discontinued from LTG can be restarted with a single oral loading dose. This was well tolerated, and therapeutic levels can be achieved within 1 to 3 h.