Edaravone (edaravone)

Edaravone is a free radical scavenger.

Edaravone is a free radical scavenger. The pathophysiology of amyotrophic lateral sclerosis (ALS) is poorly understood, but is likely to be multifactorial; one mechanism that has been proposed is an increase in oxidative stress. Biomarkers of oxidative stress (e.g., coenzyme Q10, 3-nitrotyrosine) are increased in patients with ALS.

The exact mechanism of action of edaravone in patients with ALS has not been fully elucidated, but is presumed to involve its antioxidant effects; as a free radical scavenger, the drug is thought to counter the oxidative damage that occurs in the nervous system of a patient with ALS. Edaravone has shown neuroprotective effects in animal models of ALS.

Following IV infusion of edaravone over 60 minutes, peak plasma concentrations occur at the end of the infusion. Following oral administration of the suspension, median time to peak plasma concentration occurred in approximately 0.5 hours under fasting conditions. Absolute bioavailability of the oral suspensionis about 57% compared with IV administration.

Equivalent exposure was demonstrated between the 105-mg dose of theoral suspension and the 60-mg dose of theIV formulation. Similar pharmacokinetics were observed following administration of the oral suspension via feeding tubes and by mouth. Peak plasma concentrations and systemic exposure of edaravone appear to increase in a more than dose-proportional manner.

Following multiple doses of edaravone, no accumulation has been observed.

Following oral administration of the suspension to healthy subjects 1 hour before or 8 hours after high-fat meals (800-1000 calories, 50% fat), 4 hours after low-fat meals (400-500 calories, 25% fat), or 2 hours after caloric supplement (250 calories, e.g., protein drink), less than 20% and 10% changes in peak plasma concentrations and AUC, respectively, wereobserved. Following oral administration of the suspension to healthy subjects, peak plasma concentration decreased by 82%, and AUC decreased by 61% with a high-fat meal compared to fasted conditions. Following oral administration of the suspension 4 hours after high-fat meals, peak plasma concentrations and AUC decreased by 44% and 24%, respectively.

Following oral administration of the suspension 2 hours after low-fat meals, peak plasma concentrations and AUC decreased by 45% and 21%, respectively.

Edaravone is 92% bound to serum proteins, primarily to albumin. The drug is metabolized to a sulfate conjugate presumed to be formed by sulfotransferases and to a glucuronide conjugate formed by multiple uridine diphosphate-glucuronosyltransferase (UGT) isoenzymes (i.e., UGT1A1, 1A6, 1A7, 1A8, 1A9, 1A10, 2B7, and 2B17) in the liver and kidney; both metabolites are pharmacologically inactive. In healthy individuals, 60-80% of a dose of edaravone is excreted in urine as the glucuronide conjugate, 6-8% is excreted in urine as the sulfate conjugate, and less than1%is excreted in urine as unchanged drug.

The mean terminal half-life of edaravone is 4.5-9 hours; the half-life of its metabolites ranges from 3 to 6 hours. Pharmacokinetics of edaravone are not affected by age, race (i.e., between Japanese and Caucasian individuals), or gender.

USES: Edaravone is used to treat a certain type of nerve disease called amyotrophic lateral sclerosis (ALS, also commonly called Lou Gehrig's disease). It helps to slow down the worsening of this disease. However, it is not a cure for ALS, and it does not reverse nerve damage or muscle weakness.

Generic name: edaravone
Pronunciation: (e-DAR-a-vone)
Drug class: Amyotrophic Lateral Sclerosis Agents - Antioxidants
Therapeutic class: Locomotor System

The following indications are listed for Edaravone:

• Amyotrophic Lateral Sclerosis