Topiramate Pharmacokinetics in Children with Epilepsy Aged from 6 Months to 4 Years

• Published in: Epilepsia (Copenhagen) 2004-11, Vol.45 (11), p.1448-1452
• Main Authors: Mikaeloff, Yann, Rey, Elisabeth, Soufflet, Christine, D'Athis, Philippe, Echenne, Bernard, Vallée, Louis, Bouhours, Philippe, Grinspan, Augusto, Dulac, Olivier, Pons, Gérard, Chiron, Catherine
• Format: Article
• Language: English
• Subjects: Age Factors; Anticonvulsants - blood; Anticonvulsants - metabolism; Anticonvulsants - therapeutic use; Anticonvulsants. Antiepileptics. Antiparkinson agents; Area Under Curve; Biological and medical sciences; Biological Availability; Cerebrospinal fluid. Meninges. Spinal cord; Child, Preschool; Children; Drug Administration Schedule; Drug Therapy, Combination; Epilepsy; Epilepsy - drug therapy; Epilepsy - metabolism; Female; Fructose - analogs & derivatives; Fructose - blood; Fructose - pharmacokinetics; Fructose - therapeutic use; Half-Life; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Infant; Infants; Male; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Neuropharmacology; Pharmacokinetics; Pharmacology. Drug treatments; Prospective Studies; Topiramate; Valproic Acid - blood; Valproic Acid - pharmacokinetics; Valproic Acid - therapeutic use
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.0013-9580.2004.65503.x

Purpose: To study the pharmacokinetics of topiramate (TPM) at steady state in children younger than 4 years comedicated with other antiepileptic drugs (AEDs). Methods: Twenty‐two children aged 6 months to 4 years with pharmacoresistant partial or generalized epilepsy were enrolled in an open‐label prospective study. Children were assigned to different groups according to comedication with enzyme‐inducing AEDs (n = 8), valproic acid (VPA) (n = 6), or other AEDs not known to affect drug metabolism (neutral AEDs, n = 7). One child was receiving treatment with both enzyme‐inducing AEDs and VPA. After dose titration, blood samples were collected at steady state just before and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 h after the morning dose of TPM. Pharmacokinetic parameters were determined by a noncompartmental method. Results: TPM apparent oral clearance (CL/F) was significantly higher in children taking enzyme‐inducing AEDs (85.4 ± 34.0 ml/h/kg) than in those receiving VPA (49.6 ± 13.6 ml/h/kg) or neutral AEDs (46.5 ± 12.8 ml/h/kg). Conversely, dose‐normalized areas under the plasma TPM concentration curves (0–12 h) were significantly lower in enzyme‐induced patients than in patients receiving VPA or other AEDs. Conclusions: Compared with children not receiving enzyme inducers, children younger than 4 years who receive concomitant enzyme‐inducing AEDs need higher doses (milligrams per kilogram) to achieve comparable plasma TPM concentrations.