Venous irritation related to intravenous administration of phenytoin versus fosphenytoin.
OBJECTIVE
To 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.


METHODS
Randomized, double-blind, two-period, crossover study.


METHODS
University hospital clinical research unit.


METHODS
Twelve healthy volunteers within 15% of ideal body weight and with no clinically significant abnormalities on physical examination, medical history, or laboratory assessment.


METHODS
Volunteers 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.


RESULTS
Subjects 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.


CONCLUSIONS
Fosphenytoin 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.
Jamerson
B D
BD
School of Pharmacy, University of North Carolina at Chapel Hill 27599-7360.
Dukes
G E
GE
Brouwer
K L
KL
Donn
K H
KH
Messenheimer
J A
JA
Powell
J R
JR
D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D004487:Edema / Q000139:chemically induced; D004890:Erythema / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010146:Pain / Q000139:chemically induced; D010672:Phenytoin / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives*; D010689:Phlebitis / Q000139:chemically induced*; D011537:Pruritus / Q000139:chemically induced
D010672:Phenytoin; C043114:fosphenytoin