• B D Jamerson, G E Dukes, K L Brouwer, K H Donn, J A Messenheimer, and J R Powell.
• School of Pharmacy, University of North Carolina at Chapel Hill 27599-7360.
• Pharmacotherapy. 1994 Jan 1; 14 (1): 47-52.

Study ObjectiveTo compare the frequency, severity, and time course of venous irritation after administration of a single intravenous dose of phenytoin with an equimolar dose of fosphenytoin, a water-soluble phenytoin prodrug.DesignRandomized, double-blind, two-period, crossover study.SettingUniversity hospital clinical research unit.PatientsTwelve healthy volunteers within 15% of ideal body weight and with no clinically significant abnormalities on physical examination, medical history, or laboratory assessment.InterventionsVolunteers randomly received a 30-minute infusion of phenytoin sodium 250 mg (250 mg/5 ml) or an equimolar dose of fosphenytoin 375 mg (375 mg/5 ml). Subjects returned for the crossover treatment 14-21 days later.Measurements And Main ResultsSubjects assessed venous irritation (pain, burning, itching), and investigators evaluated phlebitis (erythema, swelling, tenderness), induration, exudation, and cording. Phenytoin was associated with a significantly higher degree of pain at the infusion site in all subjects and a significant degree of phlebitis in eight subjects (p < 0.05); cording occurred in six subjects. The time course of phenytoin-induced phlebitis was bimodal. Erythema and tenderness were prominent at the end of the infusion and again at 24 hours. Cording was first noted between 24 hours and 1 week after infusion. In contrast, fosphenytoin was associated with mild pain in two subjects, one incident of phlebitis, and no erythema or cording.ConclusionsFosphenytoin administration resulted in significantly less venous irritation and phlebitis compared with an equimolar dose of phenytoin. The clinical use of this water-soluble phenytoin prodrug should minimize the frequency and severity of infusion-site reactions and should allow convenient, rapid, intravenous administration of drug, undiluted or admixed with intravenous solutions.

21 keywords...

hide…