Rapid infusion of phenytoin sodium loading doses

The use of rapid intravenous infusions of phenytoin sodium to achieve prompt plasma therapeutic concentrations of phenytoin was studied in adult epileptic patients. Six adult patients who experienced recent tonic-clonic seizures were selected for study. Four of them had not been treated with phenytoin before the study; two were on chronic phenytoin therapy but had subtherapeutic serum levels. A leading dose of phenytoin sodium (15 mg/kg in 100 ml of 0.9% sodium chloride injection) was infused at 30-50 mg/min. Blood samples were drawn before phenytoin administration, every five minutes during the infusion, and at 1, 2, 4, 8, 12, 18, and 24 hours after completion of the infusion. Adverse effects were monitored during the infusion. Pharmacokinetic variables were calculated. Patients received from 750 to 1500 mg phenytoin sodium (mean +/- S.D. = 1040.8 +/- 297.3 mg). From 5 to 30 minutes were required to reach therapeutic (10-20 micrograms/ml) serum phenytoin concentrations; concentrations peaked at 31.1 +/- 10.0 micrograms/ml. Four of the six patients had therapeutic serum concentrations at 18 hours after completion of the infusion. Adverse effects were minimal and not severe; no cardiotoxicities were noted. Phenytoin half-life was 31.2 +/- 8.4 hours, total plasma clearance was 47.2 +/- 10.7 ml/kg/hr, and volume of distribution was 1.96 +/- 0.46 liters/kg. It is concluded that rapid intravenous infusion of phenytoin appears to be a reasonably safe and effective method of rapidly reaching therapeutic phenytoin concentrations.