Abstracts

RATIONALE: Lamotrigine (LTG) has been used to treat infants with epilepsy; only sparse information regarding dosing, levels and kinetics is available. Enzyme induction and metabolism have greater impact during infancy and contribute to the difficulty of effective treatment in this age group. We reviewed our experience with infants less than 24 months old to determine the relationships between doses and serum concentrations. METHODS: Randomly selected clinic and hospital records were reviewed to find 20 infants less than 24 months of age who had been treated with lamotrigine and who met inclusion criteria of complete records for: age, weight, dose of LTG, serum concentration, concomitant medications, seizure type/s, and patient response to treatment. RESULTS: Ages ranged from 4-23 months (mean 13.7). Seven infants were treated with LTG monotherapy, 7 with concomitant enzyme inducing AEDs (EIAED), 4 with non-EIAED, 1 with VPA + EIAED, and 1 with VPA + non-EIAED. All infants except those treated with VPA were on QID schedules. The mean dose and serum concentration in the LTG monotherapy group were 13.0 mg/kg/day and 14.52 mg/L respectively. The LTG + non-EIAED group mean dose and concentration were 10.68 mg/kg/day and 7.15 mg/L. The LTG + EIAED group had a mean dose of 20.5 mg/kg/day and mean serum concentration of 5.5 mg/L. There were no significant demographic differences between groups. The dose-serum concentration ratios were consistent in all groups throughout the dose range. CONCLUSIONS: Our results suggest that serum concentrations have a linear relationship to dose. The mg/kg dose in monotherapy is nearly equal (0.9 times) to the mg/L serum concentration, e.g., a dose of 10 mg/kg/day should give a serum concentration of 9 mg/L. However, when LTG is given with concomitant EIAED the mg/kg/day dose is 3.74 times the mg/L serum concentration, e.g., a dose of 10 mg/kg/day should yield a concentration of 2.7 mg/L. Our results suggest that LTG adjunctive therapy with EIAED in infants less than 24 months may require doses of 20-30 mg/kg/day to attain serum concentrations of 5-10 mg/liter. Peak and trough serum concentrations in this group may vary by 3-4 times depending on dose schedules.