Clinical value of therapeutic drug monitoring for levetiracetam in pediatric patients with epilepsy

Abstract

PurposeTo identify pediatric patients who require therapeutic drug monitoring (TDM) of levetiracetam (LEV). MethodsWe retrospectively investigated 2413 routine therapeutic drug monitoring data on serum LEV concentration from 1398 pediatric patients (age, 0–15 years). Samples were grouped by age (infants, < 1 year; preschool children, 1–5 years; primary school children, 6–11 years; and adolescents, 12–15 years), and the LEV concentration-to-dose (CD) ratio was calculated. ResultsThe mean CD ratio was highest in adolescents (analysis of variance, p < 0.001); 22.5 % and 15.7 % higher in adolescents than in preschool children and school children, respectively (Scheffé test, p < 0.001); and higher in infants than in preschool children. Preschool children had the lowest ratio and tended to show an increase in the ratio from age 2 to 5 years. Use of enzyme-inducing antiseizure medication reduced the CD ratio by 6.1 % in infants, 12.2 % in preschool children, 5.9 % in primary school children, and 9.4 % in adolescents. The mean CD ratio was 2.7 %, 26.9 %, and 39.3 % higher in preschool children, primary school children, and adolescents with defined chronic kidney disease (CKD) than in the respective age group of patients without CKD. The therapeutic concentration range for a long-term LEV therapy was 11 to 32 μg/mL. ConclusionsLEV pharmacokinetics are significantly different between infant and preschool children, so TDM of LEV is clinically useful in these patients. In pediatric patients at higher risk for CKD, glomerular filtration rate and LEV levels should be carefully monitored.