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Phenytoin
Diagnosis & Treatment > Seizure Medications > Phenytoin > Clinical pharmacology of phenytoin
 

Clinical pharmacology of phenytoin

Absorption
The rate of absorption depends on the formulation. Generic forms of phenytoin may not be exactly equivalent to Dilantin pharmacologically.

The most common form of phenytoin is 100-mg capsules. This form has a slow and extended rate: peak plasma levels are reached in 4 to 12 hours for brand-name Dilantin. If the capsules are taken with food, peak levels will be reached over a period of 24 hours, but the availability is not affected. Approximately 85% of the administered dose is absorbed.

When the phenytoin suspension is used, the peak level occurs more quickly, within about 1½ to 3 hours.

Phenytoin is also prepared in a parenteral form. The standard injectable phenytoin is slowly absorbed. A related drug, fosphenytoin (Cerebyx), is also given parenterally. It is rapidly converted to phenytoin in the body. With Cerebyx, therapeutic levels are achieved within 10 minutes and peak levels within 90 minutes.

Distribution and metabolism
Phenytoin is 69% to 96% bound to plasma proteins (average 90%), and metabolized in the liver.

At low concentrations, elimination is proportional to the concentration. But as the concentration rises to therapeutic levels, the enzyme system in the liver can become saturated and elimination occurs at a constant rate despite the dose (zero order kinetics). The effect is that a small increase in the dose sometimes causes a large change in the level of free phenytoin in the blood.

Most phenytoin is excreted in the urine in the form of inactive metabolites. The half-life is about 22 hours, with a range of 7 to 42 hours. The half-life is shorter in children and longer in the elderly.

Because phenytoin is metabolized in the liver, people with liver disease should be treated with caution. They may have to be started at a lower dose and have their dosage increased more slowly.

Steady state
Steady state is reached after 5 to 8 days (5 to 7 half lives) of taking a stable dose of phenytoin. 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.