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Oxcarbazepine and its active metabolite, (S)-licarbazepine, exacerbate seizures in a mouse model of genetic generalized epilepsy.

Epilepsia (2014-12-10)
Tae Hwan Kim, Christopher A Reid, Steven Petrou
ABSTRACT

Oxcarbazepine (OXC), widely used to treat focal epilepsy, is reported to exacerbate seizures in patients with generalized epilepsy. OXC is metabolized to monohydroxy derivatives in two enantiomeric forms: (R)-licarbazepine and (S)-licarbazepine. Eslicarbazepine acetate is a recently approved antiepileptic drug that is rapidly metabolized to (S)-licarbazepine. It is not known whether (S)-licarbazepine exacerbates seizures. Here, we test whether OXC or either of its enantiomers exacerbates the number of spike-and-wave discharges (SWDs) in mice harboring the human γ-aminobutyric acid A receptor (GABAA)γ2(R43Q) mutation. OXC (20 mg/kg), (S)-licarbazepine (20 mg/kg), and (R)-licarbazepine (20 mg/kg) all significantly increased the number of SWDs, while their duration was unaffected. The potential for (S)-licarbazepine to exacerbate SWDs suggests that eslicarbazepine acetate should be used with caution in generalized epilepsy. Furthermore, generalized seizure exacerbation for first-, second-, and third-generation carbamazepine-based compounds is likely to occur through a common mechanism.

MATERIALS
Product Number
Brand
Product Description

USP
Valproic acid, United States Pharmacopeia (USP) Reference Standard
USP
Carbamazepine, United States Pharmacopeia (USP) Reference Standard
Supelco
Carbamazepine, Pharmaceutical Secondary Standard; Certified Reference Material
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Valproic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Carbamazepine, meets USP testing specifications
Sigma-Aldrich
Carbamazepine, powder
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2-Propylpentanoic acid
USP
Oxcarbazepine, United States Pharmacopeia (USP) Reference Standard
Supelco
Oxcarbazepine, analytical standard
Sigma-Aldrich
Oxcarbazepine, ≥98% (HPLC), solid
Supelco
Oxcarbazepine solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Oxcarbazepine, European Pharmacopoeia (EP) Reference Standard
Supelco
Carbamazepine, analytical standard
Carbamazepine, European Pharmacopoeia (EP) Reference Standard
Valproic acid, European Pharmacopoeia (EP) Reference Standard
Supelco
Valproic acid solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Carbamazepine solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®