Intravenous phenytoin loading in patients after neurosurgery and in status epilepticus. A population pharmacokinetic study.

In 49 patients treated with intravenous phenytoin after a neurosurgical procedure or because of repetitive frequent seizures, the serum concentration was measured before and 2 hours after an intravenous bolus injection. Based on these data the apparent volume of distribution and intra- and interpatient variability were determined in this representative patient population, using the statistical package NONMEM. From 5 characteristics tested (age, sex, bodyweight, serum albumin, renal function) only bodyweight was found to significantly influence the apparent volume of distribution of phenytoin. The population average was estimated as 1.0 +/- 0.04 L/kg (estimate +/- SE) and interindividual variability, expressed as coefficient of variation, was 23 +/- 6%. By means of Monte Carlo simulations an optimal dosing scheme for phenytoin loading has been calculated. Based on these results, a dose of 15 mg/kg divided into 3 intravenous injections administered 2 hours apart at a maximum rate of 50 mg/min is recommended. This loading regimen should result in therapeutic concentrations (10 to 20 mg/L) in 90% of patients within 6 hours.