Efficacy of individualized phenytoin sodium loading doses administered by intravenous infusion

The safety and efficacy of administering individualized phenytoin sodium loading doses by intravenous infusion were studied on 40 occasions in 37 adult patients having seizures. Doses were calculated based on an average volume of distribution (0.75 L/kg) and desired plasma phenytoin concentration. Total and free phenytoin concentrations were determined before and after the infusion. Phenytoin sodium doses of 225-1300 mg were administered by intravenous infusion at a rate of 40 mg/min after dilution in 0.9% sodium chloride injection to concentrations ranging from 4.5 to 13.5 mg/mL. Infusion rates were reduced if adverse effects occurred. The dosing method accurately achieved desired phenytoin concentrations (predicted mean +/- S.D. concentration, 18.3 +/- 1.6 micrograms/mL; observed mean concentration, 17.4 +/- 2.5 micrograms/mL). Postinfusion concentrations of free phenytoin ranged from 0.8 to 3.6 micrograms/mL (mean +/- S.D., 1.7 +/- 0.6 micrograms/mL). Of 21 patients evaluated for efficacy, 16 responded. A total of 45% of patients experienced pain at the infusion site, which diminished when the infusion rate was reduced. No serious cardiovascular or neurological toxicities occurred. The intravenous infusion method of administration is safe and effective and is useful for rapid achievement of therapeutic phenytoin concentrations in the emergency room setting.