| Indication | For the control of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery. |
| Pharmacodynamics | Phenytoin is an antiepileptic drug which can be useful in the treatment of epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of tonic-clonic (grand mal) seizures. Phenytoin acts to dampen the unwanted, runaway brain activity seen in seizure by reducing electrical conductance among brain cells. It lacks the sedation effects associated with phenobarbital. There are some indications that phenytoin has other effects, including anxiety control and mood stabilization, although it has never been approved for those purposes by the FDA. Phenytoin is primarily metabolized by CYP2C9. |
| Mechanism of action | Phenytoin acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. By promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of post-tetanic potentiation at synapses. Loss of post-tetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas. |
| Absorption | Bioavailability 70-100% oral, 24.4% for rectal and intravenous administration. Rapid rate of absorption with peak blood concentration expected in 1½ to 3 hours. |
| Volume of distribution | Not Available |
| Protein binding | Highly protein bound, 90% |
| Metabolism | Primarily hepatic |
| Route of elimination | Most of the drug is excreted in the bile as inactive metabolites which are then reabsorbed from the intestinal tract and excreted in the urine. Urinary excretion of phenytoin and its metabolites occurs partly with glomerular filtration but, more importantly, by tubular secretion. |
| Half life | 22 hours (range of 7 to 42 hours) |
| Clearance | Not Available |
| Toxicity | Oral, mouse: LD50 = 150 mg/kg; Oral, rat: LD50 = 1635 mg/kg. Symptoms of overdose include coma, difficulty in pronouncing words correctly, involuntary eye movement, lack of muscle coordination, low blood pressure, nausea, sluggishness, slurred speech, tremors, and vomiting. |