title: Relative bioavailability of orally administered fosphenytoin sodium injection compared with phenytoin sodium injection in healthy volunteers.
abstract: OBJECTIVE
  To describe the pharmacokinetics of fosphenytoin (FPHT) sodium injection when administered orally, and to determine the relative oral bioavailability (FREL ) of FPHT sodium injection compared with PHT sodium injection based on pharmacokinetic modeling in healthy volunteers.
  
  
  METHODS
  Open-label, randomized, single-dose, two-period, two-sequence crossover study.
  
  
  METHODS
  University-affiliated clinical research center funded by the National Center of Research Resources.
  
  
  METHODS
  Ten healthy adult volunteers.
  
  
  METHODS
  Subjects were randomized to receive a single oral dose of either PHT sodium injection or FPHT sodium injection at a dose equivalent to 400 mg PHT acid. Blood samples were collected at baseline (just prior to administration) and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after dose administration. After a 7-14-day washout period, the subjects underwent the same study procedures for administration of the other agent (PHT or FPHT).
  
  
  RESULTS
  The mean age and weight of the 10 subjects were 37 years and 72.5 kg, respectively, and the mean dose was 5.6 mg/kg based on PHT acid equivalence. The mean FREL of FPHT was 1.21 (95% confidence interval [CI] 1.07-1.35). Serum PHT concentrations were determined by fluorescence polarization immunoassay. The median (range) maximum serum concentration (Cmax ) values were significantly higher after FPHT administration compared with PHT: 10.7 (9.0-19.4) mg/L versus 5.0 (3.2-8.9) mg/L (p=0.002). The PHT concentration after oral administration of FPHT displayed faster absorption compared with PHT, with a median (range) time to reach Cmax of 1.0 (0.5-2.0) hours versus 6.0 (2.0-24.0) hours (p=0.008). All subjects completed the study without any serious adverse events reported.
  
  
  CONCLUSIONS
  FPHT sodium injection given orally was absorbed more rapidly and to a significantly greater extent than PHT sodium injection given orally to healthy volunteers. Further evaluation of oral FPHT as an alternative in patients requiring enteral feedings is warranted.
authors.affiliation: Department of Pharmacy, Denver Health Medical Center, Denver, Colorado.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Kaucher
authors.affiliation: Department of Pharmacy, University of Rochester Medical Center, Rochester, New York.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Acquisto
authors.affiliation: Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York.
authors.forename: Gauri G
authors.initials: GG
authors.lastname: Rao
authors.affiliation: Department of Surgery, University of Rochester Medical Center, Rochester, New York.
authors.forename: David C
authors.initials: DC
authors.lastname: Kaufman
authors.affiliation: Department of Pharmacy, Highland Hospital of Rochester, Rochester, New York.
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Huntress
authors.affiliation: Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York.
authors.forename: Alan
authors.initials: A
authors.lastname: Forrest
authors.affiliation: Department of Pharmacy, University of Rochester Medical Center, Rochester, New York.
authors.forename: Curtis E
authors.initials: CE
authors.lastname: Haas
mesh_terms: D000284:Administration, Oral; D000328:Adult; D018592:Cross-Over Studies; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D010672:Phenytoin; C043114:fosphenytoin
keywords: bioavailability; fosphenytoin sodium solution; phenytoin acid suspension; phenytoin sodium solution