Oxcarbazepine pharmacokinetics and tolerability in children with inadequately controlled epilepsy.
This two-part, open-label study evaluated the pharmacokinetics, safety, and tolerability of oxcarbazepine as combination therapy in 112 children 2 to 12 years old with inadequately controlled epilepsy. Part I was a pharmacokinetic study in children stratified by age (2-5 years and 6-12 years) and randomized to receive a single oxcarbazepine dose of 5 mg/kg or 15 mg/kg. Mean specific AUC and t(1/2) values of the active metabolite (MHD) were approximately 30% lower in younger children compared with older children, regardless of dose. Part II was a 4-month safety, tolerability, and pharmacokinetic study in which children received oxcarbazepine doses of 11 to 68 mg/kg/day. The mean specific oxcarbazepine daily dose was 38% higher in younger children compared with older children. Similarly, mean trough plasma MHD concentrations were 34% lower in younger children. Six (5%) children discontinued due to adverse events. Oxcarbazepine was safe and well tolerated. Younger children require higher oxcarbazepine doses because of rapid clearance.
Rey
Elisabeth
E
Hôpital St. Vincent de Paul, 74, Avenue Denfert-Rochereau, 75 674 Paris Cedex 14, France.
Bulteau
Christine
C
Motte
Jacques
J
Tran
Agnes
A
Sturm
Yvonne
Y
D'Souza
Joseph
J
Markabi
Sabri
S
Pons
Gérard
G
Dulac
Olivier
O
D000927:Anticonvulsants / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002220:Carbamazepine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D000078330:Oxcarbazepine
D000927:Anticonvulsants; D002220:Carbamazepine; D000078330:Oxcarbazepine