Topiramate pharmacokinetics in children with epilepsy aged from 6 months to 4 years.
OBJECTIVE
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.
Mikaeloff
Yann
Y
Neuropediatric Department, University Hospital, Angers, France. yann.mikaeloff@tnn.ap-hop-paris.fr
Rey
Elisabeth
E
Soufflet
Christine
C
d'Athis
Philippe
P
Echenne
Bernard
B
Vallée
Louis
L
Bouhours
Philippe
P
Grinspan
Augusto
A
Dulac
Olivier
O
Pons
Gérard
G
Chiron
Catherine
C
D000367:Age Factors; D000927:Anticonvulsants / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use*; D019540:Area Under Curve; D001682:Biological Availability; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies; D000077236:Topiramate; D014635:Valproic Acid / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose; D014635:Valproic Acid