Premium
PI‐47
Author(s) -
Toublanc N.,
Jacqmin P.,
SargentiniMaier M.,
Stockis A.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.068
Subject(s) - medicine , dosing , nonmem , pharmacokinetics , levetiracetam , concomitant , population , volume of distribution , pharmacology , epilepsy , environmental health , psychiatry
BACKGROUND To characterise levetiracetam (LEV)'s pharmacokinetics (PK) in children with epilepsy to identify demographic and/or physiological determinants of LEV, including potential influence of concomitant antiepileptic drugs (AEDs) and define optimal doses. METHODS Retrospective analysis using data pooled from 5 studies: 2319 LEV concentration‐time records and covariate information from 228 children. Population PK analysis performed using non‐linear mixed effects modeling (NONMEM). Association between PK parameters and age, gender, race, BW, mass index, surface, LEV dose, creatinine clearance and concomitant AEDs were assessed. The final population model was used for simulating different dosing regimens to achieve similar concentrations to those in adults receiving LEV 500 mg bid. RESULTS LEV clearance and distribution volume mainly related to BW and enzyme‐inducing AEDs. Simulations showed starting dosing recommendations of; 10 mg/kg solution bid and 500 mg tablet bid for BW of <50 kg and ≥50 kg respectively; alternatively, 10 mg/kg solution bid for BW <20 kg, 250 mg tablet bid for BW of 20–40 kg, and 500 mg tablet bid for BW >40 kg. CONCLUSIONS The primary predictor of LEV plasma concentrations in this paediatric population is BW. The concentration‐lowering effect of enzyme‐inducing AEDs does not entail dose adjustment. The recommended starting dose to achieve plasma concentrations similar to those from a 500 mg bid dose in adults is 10 mg/kg/bid. Clinical Pharmacology & Therapeutics (2005) 79 , P19–P19; doi: 10.1016/j.clpt.2005.12.068