Oxcarbazepine

Oxcarbazepine (Trileptal) has been approved by the FDA as monotherapy or adjuvant therapy for treating partial-onset and generalized tonic-clonic seizures in adults and children older than 6 years. It also has mood stabilizing properties and is prescribed for treatment of bipolar disorders. Oxcarbazepine is less toxic than carbamazepine.

Oxcarbazepine is a prodrug, which is metabolized in the liver to form 10-hydroxycarbamazepine (MHD). MHD is the pharmacologically active compound that accumulates in plasma. Peak concentration is reached 3 to 5 hours after oral ingestion. The elimination half life is 8-15 hours. Clearance is reduced in individuals with renal insufficiency and increased in pregnancy.

Oxcarbazepine can cause hyponatremia, especially during the first 3 months of treatment.  Therapeutic drug monitoring of MHD can be helpful in establishing an individual’s optimal plasma concentration for controlling seizures without toxicity. 

A wide range of serum concentrations, 10-35 ug/mL, have been effective in seizure treatment. Toxic side effects are more common when serum concentration exceeds 35 ug/mL. 

Oxcarbazepine is measured by liquid chromatography/tandem mass spectrometry. Therapeutic ranges are based on trough levels, collected immediately before the next dose. The therapeutic range for MHD is 10-35 ug/mL. 

Specimen requirement is one red-top tube of blood. Gel tubes are not acceptable. 

References

Lensmeyer GL, Gidal BE, Wiebe DA. Optimized high-performance liquid chromatographic method for determination of lamotrigine in serum with concomitant determination of phenytoin, carbamazepine, and carbamazepine epoxide. Ther Drug Monit. 1997;19(3):292-300.

Bourgeois BF. Pharmacokinetic properties of current antiepileptic drugs. What improvements are needed? Neurology. 2000; 55(Suppl 3):S11-S16.

Lloyd P, Flesch G, Dieterle W. Clinical pharmacology and pharmacokinetics of oxcarbazepine. Epilepsia. 1994;35(Suppl 3):S10-S13.