The Effect of Age on the Apparent Clearance of Felbamate: A Retrospective Analysis Using Nonlinear Mixed-Effects Modeling
作者:
Banfield* Christopher,
Zhu† Guang-Rui,
Jen† J.,
Jensen‡ Peder,
Schumaker§ Robert,
Perhach§ James,
Affrime* Melton,
Glue* Paul,
期刊:
Therapeutic Drug Monitoring
(OVID Available online 1996)
卷期:
Volume 18,
issue 1
页码: 19-29
ISSN:0163-4356
年代: 1996
出版商: OVID
关键词: Felbamate;Epilepsy;Carbamazepine;Valproate;Phenytoin
数据来源: OVID
摘要:
SummaryThe effects of age on felbamate apparent clearance were examined through a retrospective analysis of plasma concentration data from 700 pediatric and adult epileptic patients (age range, 2-74 years) enrolled in six clinical studies. Patients received felbamate as monotherapy or in combination with either the antiepileptic drugs (AEDs) carbamazepine (CBZ), phenytoin (PHT), or valproate (VPA). Data were analyzed using a nonlinear mixed-effects pharmacostatistical modeling technique (NONMEM). Factors in the model included age, body weight, and concomitant AEDs. Apparent clearance was highest in the very young and decreased during the early teenage years, with minimal changes observed beyond 13 years. Mean apparent clearance values were ≈40% higher in children (2-12 years) compared with those in adults (13-65 years). This pattern and its magnitude were consistent whether felbamate was administered alone or coadministered with CBZ, PHT, or VPA. The increase in clearance is minimal compared with other AEDs including PHT, CBZ, and phenobarbital. Enzyme-inducing AEDs (CBZ and PHT) increased felbamate apparent clearance by 32-38% relative to monotherapy, whereas coadministration with VPA had a minimal effect on felbamate apparent clearance. Dose/concentration linearity was observed at all ages during mono- or polytherapy. These findings suggest that felbamate dosing should be relatively uncomplicated in children relative to that in adults.
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