| Indication |
For use as adjunctive treatment of partial seizures in adults with epilepsy. |
| Pharmacodynamics |
Zonisamide is an antiseizure drug chemically classified as a
sulfonamide and unrelated to other antiseizure agents. The precise
mechanism by which zonisamide exerts its antiseizure effect is unknown,
although it is believed that the drug blocks sodium and calcium
channels, which leads to the suppression of neuronal
hypersynchronization (i.e. convulsions). Sonisamide has also been found
to potentiate dopaminergic and serotonergic neurotransmission but does
not appear to potentiate syanptic activity by GABA (gamma amino butyric
acid). |
| Mechanism of action |
Zonisamide binds to sodium channels and voltage sensitive calcium
channels, which suppresses neuronal depolarization and
hypersynchronization. Zonisamide also inhibits carbonic anhydrase to a
weaker extent, but such an effect is not thought to contribute
substantially to the drug's anticonvulsant activity. |
| Absorption |
Variable, yet relatively rapid rate of absorption with a time to
peak concentration of 2.8-3.9 hours. Food has no effect on the
bioavailability of zonisamide. |
| Volume of distribution |
|
| Protein binding |
40% (at concentrations of 1.0-7.0 µg/mL) |
| Metabolism |
Primarily hepatic through cytochrome P450 isoenzyme 3A4
(CYP3A4). Undergoes acetylation and reduction, forming N-acetyl
zonisamide, and the open-ring metabolite 2–sulfamoylacetyl phenol,
respectively. |
| Route of elimination |
Zonisamide is excreted primarily in urine as parent drug and as the glucuronide of a metabolite. |
| Half life |
63 hours |
| Clearance |
- 0.30 – 0.35 mL/min/kg [patients not receiving enzyme-inducing antiepilepsy drugs (AEDs)]
- 0.35 – 0.5 mL/min/kg [Concomitant administration of phenytoin and carbamazepine]
|
| Toxicity |
Symptoms of overdose include diminished breathing, loss of consciousness, low blood pressure, and slow heartbeat. |
