Absorption peak plasma levels are reached approximately 4-5 hours after an oral dose. Nearly the entire administered dose is absorbed. Food appears to have almost no effect on the absorption of oxcarbazepine.

Distribution and metabolism
Oxcarbazepine is chemically and structurally similar to carbamazepine, but undergoes a different metabolic process. Carbamazepine is oxidized to the 10,11 epoxide and then hydrolyzed. Oxcarbazepine undergoes reduction of the carbonyl group to form MHD by a cytosolic, non-microsomal, non-inducible keto-reductase. MHD is the active metabolite of oxcarbazepine and accounts for its antiseizure activity. The half-life of MHD averages 8 to 10 hours and is stable during chronic oxcarbazepine therapy in co-medicated patients. MHD is approximately 40% protein-bound.

Because unchanged oxcarbazepine and its metabolites are nearly entirely excreted in the urine, hepatic impairment has no apparent affect on the pharmacokinetics of oxcarbazepine or MHD. However, because oxcarbazepine metabolites are cleared renally, MHD levels are significantly increased in patients with reduced creatinine clearances. Oxcarbazepine dosages in patients with renal impairment should be reduced by 50% and the titration phase should be prolonged.

Steady state
Steady state is achieved after 3 to 4 oxcarbazepine doses in a twice-daily regimen. The dose that a patient takes should not be increased until steady state has been reached (or some time later), so that the effects of the previous dosage can be assessed.

Reviewed by Steven C. Schachter, MD
Submitted: 01/03/08