Clinical pharmacology of zonisamide
Zonisamide is absorbed rapidly and evenly distributed. Peak plasma levels of zonisamide are reached 2 to 4 hours after the capsules are taken. (These levels are 2 to 5 micrograms per milliliter if two to four 100-mg capsules are used.) If the capsules are taken with food, peak levels are not reached for 4 to 6 hours, but the availability of the medication is not affected.
Distribution and metabolism
Zonisamide binds to red blood cells and is found in a much higher concentration in red blood cells than in plasma. The concentration in plasma is greater at higher doses, perhaps because the red cells become saturated. Zonisamide is approximately 40% bound to plasma proteins. This rate is unaffected by the presence of therapeutic concentrations of phenytoin, phenobarbital or carbamazepine. Daily dosages and plasma concentrations are linearly related in adults and children.
Zonisamide is excreted primarily in the urine, so people with kidney disease should be treated with caution. The time required for the concentration of zonisamide in the blood to be reduced to half the peak level, its half-life, is about 50 to 68 hours for plasma and 105 hours for red blood cells. This is considered a long half-life. It is shortened by the presence of some other medications, however.
Because zonisamide is metabolized in the liver, people with liver disease should be treated with caution. The dose may have to be increased more slowly.
Zonisamide does not induce its own metabolism or inhibit hepatic metabolism.
Steady state (equilibrium), when the amount of drug taken is equal to the amount being metabolized and excreted, is reached after about 14 days of taking a stable dose of zonisamide. Levels in the blood then can be expected to be fairly constant. 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 dose can be assessed.