This study aimed to evaluate the safety and tolerability of intravenous (IV) levetiracetam (LEV) as a monotherapy in children aged 1 month-16 years and to explore the pharmacokinetics (PK) of IV LEV and the time to seizure after IV then oral administration of LEV in pediatric children with epilepsy. Children diagnosed with acute unprovoked seizures requiring in-hospital IV LEV administration were included. After administration, the clinical seizure outcomes, side effects, and the Korean-Child Behavior Checklist were monitored and the PK and repeated time to seizure were analyzed via modeling using NONMEM software. Overall, 37 children with epilepsy were enrolled and underwent a PK analysis (median age, 4.6 years; median weight, 18.0 kg). Nine children (24.3%) had seizure recurrence during the follow-up period (median, 3.8 months) and 5 children (13.5%) experienced LEV-associated adverse events such as irritability (n = 2; 5.4%) and somnolence (n = 3; 8.1%). The plasma LEV concentrations after IV LEV were best described by a one-compartment linear PK model. Only body weight was associated with both the clearance and volume of distribution of LEV. The Weibull distribution model described the time to seizure recurrence well; no statistically significant predictor for the time to seizure was identified. Therefore, IV LEV was a well-tolerated and effective alternative in children with acute unprovoked seizures, and models for the PK and time to repeated seizure recurrence after LEV were successfully developed. In particular, the current use of a weight-based IV LEV dosing regimen in pediatric children is practical.
Keywords: NONMEM; children; levetiracetam; modeling; seizure.
© 2018, The American College of Clinical Pharmacology.