Pharmacokinetics of phenytoin following intravenous administration in epileptic patients

The pharmacokinetics of phenytoin has been studied in 5 epileptic patients after administration of single intravenous doses (250 mg). Plasma levels at all sampling times showed high variability among individuals. Phenytoin concentrations declined over the first 1-2 hr following the injection, then rose again producing a delayed peak after about 4 hr. The decline of the log-plasma concentration with time appeared to be linear after the 6th hr. Half lives ranged from 10 to 14 hr. Apparent volumes of distribution ranged between 0.27 and 1.09 l/kg. The kinetic factors responsible for the observed large differences in plasma levels and the therapeutic implications are discussed.