Population Pharmacokinetics of Adjunctive Lacosamide in Pediatric Patients With Epilepsy
Julia Winkler1,2, Rik Schoemaker1,2, Armel Stockis3
1SGS Exprimo, Mechelen, Belgium.
Insights
This study developed a population pharmacokinetic model for lacosamide in pediatric epilepsy patients. Enzyme-inducing antiepileptic drugs significantly decreased lacosamide levels, informing optimized dosing strategies.
Area of Science:
- Pharmacokinetics
- Pediatric Pharmacology
- Epilepsy Treatment
Background:
- Lacosamide is an antiepileptic drug used in pediatric patients.
- Understanding lacosamide pharmacokinetics in children is crucial for safe and effective dosing.
- Existing pharmacokinetic data in pediatric populations are limited.
Purpose of the Study:
- To develop a population pharmacokinetic (PopPK) model for lacosamide in pediatric patients with epilepsy.
- To identify covariates influencing lacosamide pharmacokinetics in this population.
- To propose weight-based dosing strategies for pediatric patients to achieve adult-equivalent exposures.
Main Methods:
- A single-compartment PopPK model with first-order absorption and elimination was utilized.
- Data from 402 lacosamide plasma concentration-time profiles from 79 pediatric patients were analyzed.
- Allometric scaling on body weight was applied for clearance and volume of distribution.
Main Results:
- Body weight significantly influenced lacosamide clearance via allometric scaling.
- Concomitant use of enzyme-inducing antiepileptic drugs resulted in a 35% reduction in lacosamide plasma concentration.
- No significant impact of race, sex, age, or renal function on lacosamide clearance was observed.
Conclusions:
- The developed PopPK model adequately describes lacosamide disposition in pediatric epilepsy patients.
- Enzyme-inducing antiepileptic drugs necessitate dose adjustments for lacosamide in children.
- Simulated weight-based dosing schemes can help achieve target lacosamide exposures in pediatric patients aged 4-17 years.
Abstract:
A pediatric population pharmacokinetic model including covariate effects was developed using data from 2 clinical trials in pediatric patients with epilepsy (SP0847 and SP1047). Lacosamide plasma concentration-time data (n = 402) were available from 79 children with body weights ranging from 6 to 76 kg, and a balanced age distribution (6 months to <2 years: n = 14; 2 to <6 years: n = 22; 6 to <12 years: n = 25; 12 to <18 years: n = 18). A single-compartment population pharmacokinetic model with first-order absorption and elimination described the data adequately. Plasma clearance was modeled using allometric scaling on body weight with a freely estimated allometric exponent, while volume of distribution used a fixed theoretical allometric exponent. Covariate search identified a significant effect of enzyme-inducing antiepileptic drugs resulting in a 35% decrease in lacosamide average plasma concentration. No additional effects on clearance could be attributed to race, sex, age, or renal function. Different dosing adaptation schemes by body weight bands were simulated to approximate, in pediatric patients aged 4 to 17 years, the same average plasma concentration as in adult patients receiving the maximum recommended lacosamide daily dose.
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