Oral administration of fomepizole produces similar blood levels as identical intravenous dose

Clin Toxicol (Phila). 2008 Mar;46(3):181-6. doi: 10.1080/15563650701373796.


Introduction: Fomepizole is available intravenously (i.v.) for the treatment of methanol and ethylene glycol poisoning. Few studies demonstrate that fomepizole achieves effective serum concentrations after i.v. or oral (p.o.) use. The objective was to describe the comparative pharmacokinetics of fomepizole after a single p.o. and i.v. dose.

Methods: This was a prospective, randomized, crossover trial in 10 healthy volunteers. Each received 15 mg/kg fomepizole, p.o. and by 30 minute i.v. infusion. Serum was collected at 0, 0.25, 0.5, 1, 2, 4, 7, 12, 24, 36, and 48 hours (h) and stored at -70 degrees C. Candidate models were fit to the i.v. and p.o. data, simultaneously, using iterative 2-stage analysis weighted by the estimated inverse observation variance. Time above the MEC (T>MEC) was determined by numeric integration of the fitted functions using 10 micromoles/L as the minimum effective concentration (MEC).

Results: Seven females and 3 males were enrolled. Sole complaints included headache and dizziness in 3 subjects and 10/10 reported an unpleasant taste. The final PK model was 2-compartment with 0-order i.v. and 1(st)-order p.o. input (following a fitted TLag) and Michaelis-Menten elimination. p.o. fomepizole was rapidly absorbed with a bioavailability of approximately 100%. The Km was 0.935+/-0.98 micromoles/L and the Vmax was 18.57+/-9.58 micromoles/L/h. T>MEC was 32 h with agreement between p.o. and i.v. dosing.

Conclusions: This is the first study that effectively determines a human Vmax and Km for p.o. and i.v. fomepizole. p.o. and i.v. administration of fomepizole result in similar pharmacokinetic parameters.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Antidotes / administration & dosage*
  • Antidotes / metabolism*
  • Antidotes / pharmacokinetics
  • Biological Availability
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Fomepizole
  • Humans
  • Infusions, Intravenous
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Pyrazoles / administration & dosage*
  • Pyrazoles / blood*
  • Pyrazoles / pharmacokinetics


  • Antidotes
  • Pyrazoles
  • Fomepizole