Oxcarbazepine () is an antiepileptic drug available as 150 mg, 300 mg and 600 mg film-coated tablets for oral administration. Oxcarbazepine () is 10,11-Dihydro-10-oxo-5-dibenz[b,]azepine-5-carboxamide, and its structural formula is
Oxcarbazepine () is a white to faintly orange crystalline powder. It is slightly soluble in chloroform, dichloromethane, acetone, and methanol and practically insoluble in ethanol, ether and water. Its molecular weight is 252.27.
Oxcarbazepine () film-coated tablets contain the following inactive ingredients: colloidal silicon dioxide, povidone, polyethylene glycol, croscarmellose sodium, microcrystalline cellulose, crospovidone, sodium stearyl fumarate, hypromellose, polysorbate 80, titanium dioxide and yellow iron oxide.
Following oral administration of Oxcarbazepine () tablets, Oxcarbazepine () is completely absorbed and extensively metabolized to its pharmacologically active 10-monohydroxy metabolite (MHD). The half-life of the parent is about two hours, while the half-life of MHD is about nine hours, so that MHD is responsible for most antiepileptic activity.
Based on MHD concentrations, Oxcarbazepine () tablets and suspension were shown to have similar bioavailability.
After single-dose administration of Oxcarbazepine () tablets to healthy male volunteers under fasted conditions, the median t was 4.5 (range 3 to 13) hours.
In a mass balance study in people, only 2% of total radioactivity in plasma was due to unchanged Oxcarbazepine () , with approximately 70% present as MHD, and the remainder attributable to minor metabolites.
Steady-state plasma concentrations of MHD are reached within 2 to 3 days in patients when Oxcarbazepine () is given twice a day. At steady-state the pharmacokinetics of MHD are linear and show dose proportionality over the dose range of 300 to 2400 mg/day.
The apparent volume of distribution of MHD is 49L.
Approximately 40% of MHD is bound to serum proteins, predominantly to albumin. Binding is independent of the serum concentration within the therapeutically relevant range. Oxcarbazepine () and MHD do not bind to alpha-1-acid glycoprotein.
Oxcarbazepine () is rapidly reduced by cytosolic enzymes in the liver to its 10-monohydroxy metabolite, MHD, which is primarily responsible for the pharmacological effect of Oxcarbazepine () . MHD is metabolized further by conjugation with glucuronic acid. Minor amounts (4% of the dose) are oxidized to the pharmacologically inactive 10,11-dihydroxy metabolite (DHD).
Oxcarbazepine () is cleared from the body mostly in the form of metabolites which are predominantly excreted by the kidneys. More than 95% of the dose appears in the urine, with less than 1% as unchanged Oxcarbazepine () . Fecal excretion accounts for less than 4% of the administered dose. Approximately 80% of the dose is excreted in the urine either as glucuronides of MHD (49%) or as unchanged MHD (27%); the inactive DHD accounts for approximately 3% and conjugates of MHD and Oxcarbazepine () account for 13% of the dose.
