Phenytoin (Dilantin) is an anticonvulsant drug, which can be useful in the treatment of seizures and epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited, possibly by promoting sodium efflux from neurons and stabilizing the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. Loss of posttetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas. Phenytoin reduces the maximal activity of brain-stem centers responsible for the tonic phase of tonic-clonic (grand mal) seizures.

Phenytoin exhibits nonlinear, dose-dependent, Michaelis-Menten pharmacokinetics. At therapeutic levels, phenytoin enzyme hepatic metabolism reaches its capacity and its pharmacokinetics changes from first order to zero order, at which time a small increase in the daily dose will result in a disproportionately higher level. Because of its capacity-limited metabolism, phenytoin half-life and time to reach steady state are concentration dependent. The higher the concentration, the longer the half-life and the longer the time it takes to reach steady state. The plasma half-life in humans after oral administration of phenytoin averages 22 hours, with a range of 7 to 42 hours. After intravenous (IV) administration, the half-life ranges between 11 and 15 hours. The difference in half-life is due to slower absorption and varying bioavailability of phenytoin formulations. Drug interactions may increase or decrease phenytoin half-life. Estimation of time to reach steady state cannot be based on half-life. Serum level determinations should be obtained after treatment initiation, dosage change, or addition or subtraction of an interacting food or drug to the regimen. Trough levels provide information about clinically effective serum level range and are obtained just prior to the patient’s next scheduled dose. Peak levels indicate an individual’s threshold for emergence of dose-related side effects and are obtained at the time of expected peak concentration. For Dilantin capsules, peak serum levels occur 4 to 12 hours after administration. For Dilantin Infatabs and Dilantin suspension, peak serum levels occur 1.5 to 3 hours after administration. The timing of levels is dependent on the clinical situation as well
as route of administration and dosage form. In the acute setting, it is advisable to check non-steady-state phenytoin levels to avoid subtherapeutic or toxic levels prior to reaching steady state. Suggested sampling time after oral load is in 24 hours. Because of slow absorption of oral formulations, timing is not critical for level monitoring, but trough levels are suggested. Suggested sampling time for IV maintenance is also a trough level (or just prior to the next dose). Though beyond the scope of this review, detailed pharmacokinetic equations are available to help dose and monitor phenytoin treatment. (See suggested readings.)