Oxcarbazepine Metabolite 10-Hydroxycarbazepine, Serum/Plasma

Trileptal

10-Hydroxycarbazepine

Oxcarbazepine (trileptal) is an anti-convulsant used for treating generalized tonic-clonic and partial seizures. It can be administered alone or as an adjunct to other anti-convulsants. Clinically significant effects of oxcarbazepine are observed when plasma levels of its active metabolite, 10-OH-carbazepine, are between 15 and 35 µg/mL. Toxic symptoms may occur when plasma levels exceed 35 µg/mL. The therapeutic monitoring of oxcarbazepine and its active metabolite are important for achieving proper serum/plasma concentration to inhibit epileptic seizures and avoid adverse effects. The precise mechanism of the action by which oxcarbazepine and its active metabolite exert their antiseizure effect is unknown. However, in vitro electro-physiological studies indicate that they produce blockade of voltage-sensitive sodium channels, resulting in the stabilization of hyperexcited neural membranes, inhibition of repetitive neuronal firing, and diminution of propagation of synaptic impulses. These are important in prevention of seizure spread in the brain. In addition, the increased potassium conduction and calcium channel activities may contribute to the antiseizure treatment effects. After oral administration, oxcarbazepine is readily absorbed in the body, followed by rapid and almost complete metabolization to 10-OH-carbazepine, active metabolite. The half-life of oxcarbazepine is only 1 to 2.5 hours, while that of 10-OH-carbazepine is 11 to 15 hours. The protein binding of oxcarbazepine is about 67%, whereas that of the metabolite is about 38%. The clearance of oxcarbazepine and its active metabolite from the body is mainly through ketone reduction and O-site conjugation with glucuronic acid rather than oxidative processes via cytochrome P450 system. More than 95% of the treatment dosage is excreted by the kidneys. Fecal excretion only accounts for less than 4%.