Topiramate pharmacokinetics in infants and young children: Contribution of population analysis
| Autor: | Rima Nabbout, Vincent Jullien, Catherine Chiron, Stéphanie Chhun, Elisabeth Rey, Olivier Dulac, Gérard Pons, Marion Bouillon-Pichault |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Topiramate Databases Factual medicine.medical_treatment Population Fructose Body weight Population estimate Animal science Pharmacokinetics Humans Medicine education education.field_of_study Models Statistical business.industry Dosing regimen Infant Regimen Anticonvulsant Neurology Area Under Curve Child Preschool Anesthesia Anticonvulsants Female Neurology (clinical) business Monte Carlo Method Algorithms Forecasting medicine.drug |
| Zdroj: | Epilepsy Research. 93:208-211 |
| ISSN: | 0920-1211 |
| DOI: | 10.1016/j.eplepsyres.2010.12.004 |
| Popis: | Summary Purpose To determine the range of topiramate (TPM) concentrations obtained in children under 4 with the recommended dosage regimen (3–9mg/kg/day) and to compare them to adult target ranges. Methods The population pharmacokinetic model developed for TPM, with/without enzyme inducer antiepileptic drugs (EIAEDs) in children was used to determine dosage regimens providing AUC and trough concentrations ( C trough s) within the adult ranges. Results TPM pharmacokinetics was described by a one-compartment model. EIAEDs increased the apparent clearance (CL/F) and age and body weight increased the apparent distribution volume (Vd/F). Mean population estimates (% CV interindividual variability) were 0.608/1.15L/h (13%) for CL/F without/with EIAEDs, 28.6L (0.2%) for Vd/F and 1.4h −1 (124%) for the absorption rate constant. Mean AUC 0–12h reached with a 2mg/kg/day dosing regimen was within described range. A 6–16mg/kg/day dose depending on age allowed reaching target C trough range with the highest probability. Combined EIAEDs led to a 2- and 3-fold decrease in AUC and C trough , respectively. Conclusion TPM dosage of 2/4mg/kg/day (without/with EIEADs, respectively) provides the AUC reported in adults. In children under 4, alternative dosing regimen should be considered mainly when associated to EIAED to reach C trough comparable to adult values. |
| Databáze: | OpenAIRE |
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