Study objective: The elimination kinetics of ethylene glycol (EG) in human
subjects treated with fomepizole (4-methylpyrazole) were analyzed to establ
ish the efficacy of alcohol dehydrogenase (ADH) inhibition and to character
ize elimination pathways.
Methods: Drug concentration data from patients enrolled in the EG arm of th
e Methylpyrazole for Toxic Alcohols trial, a prospective, multicenter, open
-label trial of fomepizole, were analyzed and compared with published estim
ates.
Results: In 19 patients analyzed (EG concentrations of 3.5 to 211 mg/dL), e
limination was first order during fomepizole monotherapy (half-life of 19.7
+/-1.3 hours) and was not affected by the presence of ethanol, The eliminat
ion rate was significantly faster (half-life of <8.6+/-1.1 hours, P<.001) i
n the absence of fomepizole and ethanol, EG elimination by the kidneys was
directly proportional to remaining renal function as estimated by creatinin
e clearance, with a fractional excretion of 25.5%+/-9.4%. Renal elimination
and hemodialysis were the only significant routes of EG elimination as lon
g as fomepizole concentrations were maintained well above 10 mu mol/L (EG/f
omepizole molar ratio, <100:1). All patients with normal serum creatinine c
oncentrations at the initiation of fomepizole treatment had rapid rates of
renal elimination (half-life of 16.8+/-0.8 hours).
Conclusion: At doses used, fomepizole effectively inhibits ADH-mediated met
abolism of EG, Serum creatinine concentration at presentation and creatinin
e clearance can be used to predict EG elimination during fomepizole therapy
and can help determine which patients will require hemodialysis to expedit
e EG elimination. An absolute EG concentration above 50 mg/dL should no lon
ger be used as an independent criterion for hemodialysis in patients treate
d with fomepizole.