Population Pharmacokinetics of Stiripentol in Paediatric Patients with Dravet Syndrome Treated with Stiripentol, Valproate and Clobazam Combination Therapy
| Autor: | Stéphanie Chhun, Elisabeth Rey, Sophie Peigné, Christelle Rodrigues, Vincent Jullien, Gérard Pons, Michel Tod, Catherine Chiron |
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| Rok vydání: | 2017 |
| Předmět: |
Male
medicine.medical_specialty Clobazam Combination therapy Adolescent Genotype Population Epilepsies Myoclonic Pharmacology 030226 pharmacology & pharmacy Gastroenterology Models Biological 03 medical and health sciences Epilepsy 0302 clinical medicine Pharmacokinetics Dravet syndrome Internal medicine medicine Stiripentol Humans Pharmacology (medical) education Child Volume of distribution education.field_of_study business.industry Valproic Acid Infant Dioxolanes medicine.disease Cytochrome P-450 CYP2C19 Child Preschool Anticonvulsants Drug Therapy Combination Female business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Clinical pharmacokinetics. 57(6) |
| ISSN: | 1179-1926 |
| Popis: | The aim of this study was to describe the pharmacokinetics of stiripentol in children with Dravet syndrome and to determine the concentrations of stiripentol achieved in this population for the usual 25 mg/kg twice-daily dose. Thirty-five children with epilepsy were included in a prospective population pharmacokinetic study (using MONOLIX software). Four blood samples were drawn per patient. Stiripentol area under the plasma concentration–time curve (AUC) values and trough concentrations were simulated for 7000 theoretical children weighing between 10 and 70 kg for the 25 mg/kg twice-daily dose. The pharmacokinetics of stiripentol was described using a one-compartment model with zero-order absorption and first-order elimination. The apparent clearance (CL/F) and apparent volume of distribution (V d/F) of stiripentol were related to body weight by allometric equations. A dose-dependent non-linearity was also observed with an allometric model relating CL/F to the weight-normalised dose. Mean population estimates (% inter-individual variability) were 4.2 L/h (21%) for CL/F and 82 L (25%) for V d/F. The AUC of stiripentol increased by 300% when body weight increased from 10 to 70 kg. This population pharmacokinetic model of stiripentol in children with Dravet syndrome confirmed the dose-dependent non-linearity that has been evidenced in adults. It also supported that a 25 mg/kg twice-daily dose might lead to excessive exposure in children >30 kg, suggesting an eventual dose adjustment during adolescence. This study is part of the STIPOP study (EUDRACT number: 2007-001784-30). |
| Databáze: | OpenAIRE |
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