How to handle a missed or delayed dose of lacosamide in pediatric patients with epilepsy? a mode-informed individual dosing.
Epilepsy Behav
; 151: 109601, 2024 Feb.
Article
en En
| MEDLINE
| ID: mdl-38194771
ABSTRACT
This study aims to investigate the effects on the pharmacokinetic (PK) of lacosamide (LCM), and to guide the individual dosing regimens for children and ones with poor medication adherence. Population PK research was performed based on 164 plasma samples of 113 pediatric patients aged from 1.75 to 14.42 years old. The PK characteristic of LCM was developed by a one-compartment model with first-order elimination. The typical value of apparent clearance (CL) and apparent volume of distribution (Vd) was 1.91 L·h-1 and 56.53 L respectively. In the final model, the variability of CL was significantly associated with the body surface area (BSA) and elevated uric acid (UA) level. In contrast, the impact of some prevalent anti-seizure medicines, such as valproic acid, levetiracetam, oxcarbazepine, lamotrigine, and perampanel, and gene polymorphisms of Cytochrome P450 (CYP)2C19, ATP-binding cassette (ABC)B1, and ABCC2 had no clinical significance on the PK parameters of LCM. BSA-based dosing regimen of LCM was provided according to Monte Carlo simulation approach; while the dosage should reduce half in patients with an UA level of more than 400 µmol·L-1 comparing with an UA level of 100 µmol·L-1. Individualize remedial doses of about 0.5- to 1.5-fold of regular doses were recommended in six common scenarios of missed or delayed doses, that depended on the delayed time. In current study, the population PK model of LCM in children with epilepsy was developed successfully. The BSA-based dosing regimen and individualized remedial strategy were recommended to guarantee the precise administration of LCM.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Epilepsia
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
/
Child
/
Child, preschool
/
Humans
/
Infant
Idioma:
En
Revista:
Epilepsy Behav
Asunto de la revista:
CIENCIAS DO COMPORTAMENTO
/
NEUROLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos