| 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 |
| Pharmacodynamics |
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. |
| Absorption |
Rapid and complete |
| Volume of distribution |
|
| Protein binding |
Not Available |
| Metabolism |
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. |
| 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. |
| Half life |
The plasma half-life of Antizol varies with dose, even in patients with normal renal function, and has not been calculated. |
| Clearance |
Not Available |
| Toxicity |
Headache, nausea, dizziness |
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