Phenytoin is an important medication for the treatment of primary and secondary generalized tonic–clonic seizures, partial seizures, and status epilepticus. Consistent serum concentrations of phenytoin are essential for maintaining effective seizure control. Phenytoin, however, has several properties including nonlinear pharmacokinetics, a narrow therapeutic window, and uneven absorption that pose challenges for maintaining steady serum concentrations. Consistent administration and formulation will reduce the variability.

Phenytoin’s metabolism has nonlinear (Michaelis-Menten) kinetics. At low serum concentrations, a fixed percentage of drug is metabolized in a given time (first-order kinetics). At higher serum levels (at the high end of the normal therapeutic range), a fixed amount of drug is metabolized per unit time (zero-order kinetics), because the metabolic pathways are saturated. Consequently, when serum levels are high, even a small dose increase may produce a very big increase in serum levels. Additionally, factors such as hepatic dysfunction and fever can alter phenytoin clearance. Phenytoin interacts with many drugs, which may increase or decrease concentrations of it or other concomitantly used anticonvulsants.