Population pharmacokinetics of valproate in Mexican children with epilepsy

Abstract

Total body weight, daily dose of valproate and concomitant therapy with PB are factors that significantly influence VPA kinetic disposition and they should be considered in programming dosage regimens for this antiepileptic drug in the pediatric population. The validation of the model supports its acceptability for clinical purposes.

Population pharmacokinetic of antiepileptic drugs in different populations

“…However, our research clearly showed that the age within the subpopulations of children and adults was not important characteristic that influenced the clearance of valproate which is in accordance with reports by other authors [15,[18][19][20]23]. Moreover, some researchers have noted that body weight is a better indicator of metabolic capacity and general physiological condition of the body then age [21,24].…”

“…Furthermore, the current study reported an increase in VPA clearance in the adult population when phenobarbital was included in therapy. Similar results were obtained by other researchers [15,19,21,22]. The magnitude of its effect was different and ranged from 10% to 40% in a heterogenous and adult population, respectively [15,19].…”

“…Total body weight is an important cause of interindividual variability of pharmacokinetics of valproate, particularly in the children populations. The significant influence of this factor has been confirmed in studies by other authors that reports point to the possibility of both linear and non-linear increase in VPA clearance with increasing body weight of patients in different populations [15,16,[18][19][20][21]. Also, numerous studies have showed the existence of a linear increase of VPA clearance with body weight in mixed populations of children and adults [6,22].…”

Population Pharmacokinetics of Valproic Acid in Adult Chinese Epileptic Patients and its Application in an Individualized Dosage Regimen

“…which satisfy the above 2 features. [6][7][8]11,12 This relationship is consistent with the concept of the concentration-dependent binding of VPA to proteins. Patient demographic and medication details were also carefully recorded, which imparted greater accuracy and reliability to the data used in the VPA model.…”

Implications of pharmacogenetics for the therapeutic use of antiepileptic drugs

“…Considering the data summarized in our tables, only 3 [74,75,99] out of 74 studies were performed using model-based methodologies. Sallas et al applied a non-linear mixed effects modeling technique to evaluate the interactions of oxcarbazepine with other AEDs in children [102], while Correa et al developed a model describing the factors that affect the clearance of valproate in Mexican pediatric patients using sparse serum concentrations from routine clinical care [103]. More recently, Falcão et al [104] have shown the use of modeling and simulation to evaluate the influence of patient characteristics and concomitant AEDs on the PK variability of eslicarbazepine.…”