indication

Antizol is indicated as an antidote for ethylene glycol (such as antifreeze) or methanol poisoning, or for use in suspected ethylene glycol or methanol ingestion, either alone or in combination with hemodialysis

pharmacology

Fomepizole is a competitive inhibitor of alcohol dehydrogenase, the enzyme that catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites. Ethylene glycol is first metabolized to glycoaldehyde which then undergoes further oxidation to glycolate, glyoxylate, and oxalate. It is glycolate and oxalate that are primarily responsible for the metabolic acidosis and renal damage that are seen in ethylene glycol poisoning. {01}{03} Methanol is first metabolized to formaldehyde and then undergoes subsequent oxidation via formaldehyde dehydrogenase to become formic acid. It is formic acid that is primarily responsible for the metabolic acidosis and visual disturbances that are associated with methanol poisoning.

mechanism of action

Antizol (fomepizole) is a competitive inhibitor of alcohol dehydrogenase. Alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde. Alcohol dehydrogenase also catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites.

toxicity

Headache, nausea, dizziness

biotransformation

Primarily hepaticm the primary metabolite is 4-carboxypyrazole (approximately 80 to 85% of an administered dose). Other metabolites include 4-hydroxymethylpyrazole and the N -glucuronide conjugates of 4-carboxypyrazole and 4-hydroxymethylpyrazole.

absorption

Rapid and complete

half life

The plasma half-life of Antizol varies with dose, even in patients with normal renal function, and has not been calculated.

route of elimination

In healthy volunteers, only 1-3.5% of the administered dose of Antizol® (7-20 mg/kg oral and IV) was excreted unchanged in the urine, indicating that metabolism is the major route of elimination. In humans, the primary metabolite of Antizol® is 4-carboxypyrazole (approximately 80-85% of administered dose), which is excreted in the urine. The metabolites of Antizol® are excreted renally.