Clinical experience with topiramate dosing and serum levels in patients with epilepsy.
OBJECTIVE
To investigate the relevance of serum topiramate (TPM) levels (SL) monitoring in the clinical management of epileptic patients.


METHODS
Twenty-seven patients with different epileptic syndromes on TPM therapy were studied. TPM was used as add-on in 26 patients, only in one as monotherapy de novo; one case changed from TPM as add-on to TPM monotherapy. The mean follow-up time was 11 months. TPM SL were measured by fluorescence polarization immunoassay.


RESULTS
We analyzed the TPM SL in 43 samples from 27 patients. Mean TPM dose was 3.9mg/kg, mean TPM SL 13.43mumol/l. The mean level to dose ratio (LDR) was 3.63mumol/l/mg/kg. Four patients became seizure-free, all with TPM dosages lower than the mean. Eleven patients had at least 50% seizure reduction. The comedication with enzyme-inducing AED significantly reduced TPM SL and LDR. On the other hand, the influence of valproic acid (VPA) on TPM LDR was not univocal. Indeed, patients younger than 15 years showed SL values lower than the adults did, although not significant.


CONCLUSIONS
We could not detect a direct relationship between high TPM SL and efficacy neither between high TPM SL and tolerability. However, the data we collected seem to favour the hypothesis that high TPM dosage and SL might be associated to a greater probability to reduce seizure severity.
Zanotta
Nicoletta
N
Clinical Neurophysiology Unit, IRCCS E. Medea, Via Don L. Monza 20, 23842 Bosisio Parini (Lc), Italy. nzanotta@bp.lnf.it
Raggi
M Elisabetta
ME
Radice
Lucia
L
Degrate
Alessandro
A
Bresolin
Nereo
N
Zucca
Claudio
C
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012044:Regression Analysis; D000077236:Topiramate
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose