Modeling and simulation for the evaluation of dose adaptation rules of intravenous lacosamide in children.

A combined adult and pediatric population pharmacokinetic model including covariate effects was developed; simulations were subsequently performed to guide intravenous pediatric dosing adaptations. Two pharmacokinetic trials with sparse blood sampling were conducted in children with epilepsy and two trials in healthy adults with serial blood sampling. Lacosamide plasma concentration-time data were available from 43 healthy adults (18-45 years of age; body weight 50-101 kg; n = 1735 concentration vs time records), and from 79 children with epilepsy (6 months-17 years of age; body weight 6-76 kg; n = 402 concentration vs time records), with 14, 22, 25 and 18 participants in age groups <2 years, 2 to <6 years, 6 to <12 years and 12 to <18 years, respectively. A two-compartment population pharmacokinetic model was developed using nonlinear mixed effects modeling. Plasma clearance was scaled using a fixed allometric exponent on body weight, while central volume of distribution used a freely estimated allometric exponent. The model-based pharmacokinetic predictions suggested that there is no need to adapt the recommendations regarding intravenous infusion durations in children compared with adults.