Modeling and simulation for the evaluation of dose adaptation rules of intravenous lacosamide in children
Autor: | Julia Winkler, Armel Stockis, Rik C. Schoemaker |
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Rok vydání: | 2019 |
Předmět: |
Adult
Male 0301 basic medicine Pediatrics medicine.medical_specialty Adolescent Lacosamide Models Biological Young Adult 03 medical and health sciences Epilepsy 0302 clinical medicine Pharmacokinetics Covariate Humans Medicine Computer Simulation Dosing Child Dose-Response Relationship Drug business.industry Body Weight Age Factors Middle Aged medicine.disease NONMEM 030104 developmental biology Neurology Child Preschool Administration Intravenous Anticonvulsants Female Neurology (clinical) business 030217 neurology & neurosurgery Pediatric population medicine.drug Blood sampling |
Zdroj: | Epilepsy Research. 149:13-16 |
ISSN: | 0920-1211 |
Popis: | A combined adult and pediatric population pharmacokinetic model including covariate effects was developed; simulations were subsequently performed to guide intravenous pediatric dosing adaptations. Two pharmacokinetic trials with sparse blood sampling were conducted in children with epilepsy and two trials in healthy adults with serial blood sampling. Lacosamide plasma concentration-time data were available from 43 healthy adults (18-45 years of age; body weight 50-101 kg; n = 1735 concentration vs time records), and from 79 children with epilepsy (6 months-17 years of age; body weight 6-76 kg; n = 402 concentration vs time records), with 14, 22, 25 and 18 participants in age groups2 years, 2 to6 years, 6 to12 years and 12 to18 years, respectively. A two-compartment population pharmacokinetic model was developed using nonlinear mixed effects modeling. Plasma clearance was scaled using a fixed allometric exponent on body weight, while central volume of distribution used a freely estimated allometric exponent. The model-based pharmacokinetic predictions suggested that there is no need to adapt the recommendations regarding intravenous infusion durations in children compared with adults. |
Databáze: | OpenAIRE |
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