Drug/Small Molecule:

oxcarbazepine

Overview

Generic Names:	Oxcarbamazepine
IUPAC Name:	5-oxo-6H-benzo[b][1]benzazepine-11-carboxamide
Trade Names:	Trileptal
PharmGKB Accession Id:	PA450732

Description

Oxcarbazepine is structurally a derivative of carbamazepine, adding an extra oxygen atom to the benzylcarboxamide group. This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia occasionally associated with carbamazepine. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine - sodium channel inhibition - and is generally used to treat partial seizures in epileptic children and adults.

Indication

For use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults with epilepsy and as adjunctive therapy in the treatment of partial seizures in children ages 4-16 with epilepsy.

ATC Therapeutic Category

• N03AF:Carboxamide derivatives

Pharmacology and Interactions

Mechanism Of Action

The exact mechanism by which oxcarbazepine exerts its anticonvulsant effect is unknown. It is known that the pharmacological activity of oxcarbazepine occurs primarily through its 10-monohydroxy metabolite (MHD). In vitro studies indicate an MHD-induced blockade of voltage-sensitive sodium channels, resulting in stabilization of hyperexcited neuronal membranes, inhibition of repetitive neuronal discharges, and diminution of propagation of synaptic impulses.

Pharmacology

Oxcarbazepine is structurally a derivative of carbamazepine, adding an extra oxygen atom to the benzylcarboxamide group. This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia occasionally associated with carbamazepine. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine - sodium channel inhibition - and is generally used to treat the same conditions.

Food Interactions

Take without regard to meals. Avoid alcohol.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Oxcarbazepine is completely absorbed and extensively metabolized to its pharmacologically active 10-monohydroxy metabolite (MHD). MHD is metabolized further by conjugation with glucuronic acid.

Protein Binding

Approximately 40% of the active 10-monohydroxy metabolite (MHD) is bound to serum proteins, predominantly to albumin. Neither oxcarbazepine nor its MHD binds with alpha-1–acid blycoprotein.

Absorption

Completely absorbed following oral administration. Food has no effect on the rate and extent of absorption of oxcarbazepine.

Half Life

The half-life of the parent is about 2 hours, while the half-life of MHD is about 9 hours, so that MHD is responsible for most anti-epileptic activity.

Toxicity

Isolated cases of overdose with oxcarbazepine have been reported. The maximum dose taken was approximately 24,000 mg. All patients recovered with symptomatic treatment.

Chemical Properties

Chemical Formula:

C₁₅H₁₂N₂O₂

SMILES Code:

c1ccc2c(c1)CC(=O)c3ccccc3N2C(=O)N

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

252.268 / 252.0899

Curated Annotations ()

1. rs2304016 at chr2:165876749 in SCN2A, SCN2A2
   The A allele of this SNP was associated with resistance to sodium channel-blocking anti-epileptic drugs in a Chinese patient population.

   Variant Name:

   SCN2A:IVS7-32A>G

   Related Drugs:

   carbamazepine, lamotrigine, oxcarbazepine, phenytoin, topiramate

   Related Diseases:

   Epilepsy

   Evidence:

   PMID:18784617
   

Curated Information

The following genes are in curated knowledge about this drug.

	Gene	Relationship	Evidence
	CYP3A4	PK	Publications
	NR1I2	FA	Publications
	SCN2A		Variants
	SCN2A2		Variants

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Metabolizing Enzymes

• CYP2C19

Drug Targets

• SCN5A

Curated Information

The following drugs are in curated knowledge about this drug.

	Drug	Relationship	Evidence
	donepezil	PK	Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

cyclosporine	Oxcarbazepine decreases the effect of cyclosporine
ethinyl estradiol	Oxcarbazepine decreases the effect of the contraceptive
ethotoin	Oxcarbazepine increases the effect of hydantoin
felodipine	Oxcarbazepine decreases the levels of felodipine
fosphenytoin	Oxcarbazepine increases the effect of hydantoin
mephenytoin	Oxcarbazepine increases the effect of hydantoin
mestranol	Oxcarbazepine decreases the effect of the contraceptive
phenytoin	Oxcarbazepine increases the effect of hydantoin

Curated Information

The following diseases are in curated knowledge about this drug.

	Disease	Relationship	Evidence
	Epilepsy	PD       GN	Publications, Variants

LinkOuts

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.