TOPIRAMATE SERUM CONCENTRATIONS ARE INFLUENCED BY AGE AND COMEDICATION IN CHILDREN WITH EPILEPSY
Abstract number :
1.266
Submission category :
Year :
2003
Submission ID :
660
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Maria G. Dahlin, Inger öhman Departments of Woman and Child Health, Karolinska Institute, Stockholm, Sweden; Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
Rationale: Topiramate (TPM) is a broad-spectrum antiepileptic drug (AED). It has shown efficacy in reducing seizure frequency in adults and children with epilepsy. Studies have shown a higher clearance of TPM in children compared to adults. Enzyme-inducing AEDs have been found to increase the clearance of TPM. The aim of this study was to examine the influence of age as well as comedication on the serum concentrations of topiramate in a larger cohort of children with epilepsy.
Methods: In a retrospective study, 91 children with epilepsy treated with TPM were evaluated concerning the dosing and serum concentrations of topiramate as well as of their concomitant AEDs. The clearance of TPM was calculated as the weight-normalized TPM dose (mg/kg/day) divided by the steady-state plasma drug level of the child. The clearance was related to age and type of comedication. The children were divided into 4 age groups; 0-4 (n=23), 5-8 (n=24), 9-12 (n=26) and 13-17 (n=18) years. TPM was given with an AED enzyme inducer (n=32), with a nonenzyme inducer (n=49), or as monotherapy (n=10).
Results: The TPM plasma levels were linearly related to the TPM doses regardless of concomitant AEDs over a dose range from 1 to 13 mg/kg/day. The clearance of TPM in children 0-8 years compared to those 9-17 years was more than 2-fold higher if treated with an enzyme-inducing AED and about 1.5-fold higher if treated with a nonenzyme-inducing AED. Thus, in these younger age groups, clearance of TPM was significantly higher compared to the older age groups. Children receiving AED enzyme inducers had a more than 2-fold higher clearance in comparison with those who were not. Within all four age groups, highly significant differences in clearance was found between those receiving AED enzyme inducers compared to those receiving nonenzyme inducers or monotherapy.
Conclusion: In infants and children, the serum concentrations of TPM are highly dependent on age as well as type of comedication. This has to be taken into account in scheduling the dosing regime to achieve the full benefits of the therapy in individual patients.