Population pharmacokinetics of valproic acid in pediatric patients with epilepsy: considerations for dosing spinal muscular atrophy patients.

ABSTRACT: Valproic acid (VPA) dosing strategies used in recent clinical trials in patients with spinal muscular atrophy (SMA) have utilized a paradigm of monitoring trough levels to estimate drug exposure with subsequent dose titration. The validity of this approach remains uncertain and could be improved by understanding sources of pharmacokinetic variability. A population pharmacokinetic analysis of VPA in pediatric patients with epilepsy was recently performed. The pooled data set included 52 subjects with epilepsy, ages 1 to 17 years, who received intravenous and/or various oral formulations. The data was best fit by a 2-compartment model; inclusion of age and weight reduced intersubject variability for clearance (41%), central volume (70%), and peripheral volume (42%) over the base model. The f

SUBMITTER: Williams JH 

PROVIDER: S-EPMC3345311 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature