A comparison of phenytoin-loading techniques in the emergency department

Acad Emerg Med. 2004 Mar;11(3):244-52. doi: 10.1111/j.1553-2712.2004.tb02204.x.


Objectives: To compare the effectivenesses of three phenytoin-loading techniques.

Methods: Patients with subtherapeutic phenytoin concentrations who presented within 48 hours of a seizure were randomized to receive either 20 mg/kg of oral phenytoin (PO), divided in maximum doses of 400 mg every two hours, 18 mg/kg of intravenous phenytoin (IVP) at an initial infusion rate of 50 mg/min, or 18 mg/kg (phenytoin equivalents) of intravenous fosphenytoin (IVF) at an initial infusion rate of 150 mg/min.

Results: A total of 45 patients were enrolled: 16 in the PO group, 14 in the IVP group, and 15 in the IVF group. The times required to reach therapeutic drug concentrations were (mean +/- standard deviation [SD]) 5.62 +/- 0.28 hours, 0.24 +/- 0.3 hours, and 0.21 +/- 0.28 hours, respectively. A total of 17, 27, and 32 adverse drug events were observed in the PO, IVP, and IVF groups, respectively, with significantly fewer events in the PO group (p = 0.02, p = 0.01). No significant difference was found between the numbers of necessary adjustments to the infusions in the two IV groups. The average time to safe emergency department discharge was significantly shorter for the IV groups compared with the PO group (p < 0.001).

Conclusions: Oral loading has fewer adverse drug events than either IV loading method, but its use may be limited when therapeutic concentrations are required quickly. Although IVF loading is faster, from an adverse-drug event perspective, no advantage of IVF over IVP was apparent.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Anticonvulsants / administration & dosage*
  • Anticonvulsants / pharmacokinetics
  • Area Under Curve
  • Dose-Response Relationship, Drug
  • Emergency Medical Services / methods*
  • Female
  • Humans
  • Infusions, Intravenous
  • Length of Stay
  • Male
  • Outcome and Process Assessment, Health Care
  • Phenytoin / administration & dosage*
  • Phenytoin / analogs & derivatives*
  • Phenytoin / pharmacokinetics
  • Prospective Studies
  • Seizures / drug therapy*
  • Treatment Outcome


  • Anticonvulsants
  • Phenytoin
  • fosphenytoin