An Open-label, Single-dose Study to Evaluate the Pharmacokinetic Variables of Edaravone in Subjects with Mild, Moderate, or No Renal Impairment

Nakamaru, Yoshinobu; Kakubari, Masae; Yoshida, Kaori; Akimoto, Mami; Kondo, Kazuoki

doi:10.1016/j.clinthera.2020.06.020

Cited by 4 publications

(6 citation statements)

References 9 publications

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“…No extra precautionary measures have yet been advised for its use in the elderly population. Finally, this drug is not contraindicated in renal or hepatic impairment patients [ 13 - 14 ]. The most commonly reported side effects include bruising and gait disturbances.…”

Section: Reviewmentioning

confidence: 99%

“…The most commonly reported side effects include bruising and gait disturbances. They are followed by headaches, skin-related conditions (itching, blisters, reddening, rash, dermatitis, and eczema), and glycosuria in a few cases [ 14 - 16 ]. Nevertheless, based on the data that have been made available, Edaravone is generally considered safe for use.…”

Section: Reviewmentioning

confidence: 99%

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Investigating Edaravone Use for Management of Amyotrophic Lateral Sclerosis (ALS): A Narrative Review

Neupane¹,

Thada²,

Singh³

et al. 2023

Cureus

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The use of Edaravone, given orally, for the treatment of amyotrophic lateral sclerosis (ALS) was officially approved by the Federal Drug Association (FDA) in 2017. ALS is a rare and progressive degenerative disease that worsens over time. It attacks and destroys the nerve cells that control voluntary muscles, thus leading to weakness, eventual paralysis, and, ultimately death. Edaravone was given initially intravenously, but recent evidence shows better results with oral suspension. This narrative review is aimed to investigate the benefit of Edaravone for the management of ALS, compare it to Riluzole, discuss its mechanism of action, route of use, and side effects, and ultimately discuss future implications of this pharmacotherapy.

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Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Investigating Edaravone Use for Management of Amyotrophic Lateral Sclerosis (ALS): A Narrative Review

Neupane¹,

Thada²,

Singh³

et al. 2023

Cureus

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“…34 No clinically significant differences in the edaravone pharmacokinetic profiles were observed in subjects with mild or moderate renal impairment when compared with subjects with no renal impairment. 34 Efficacy and safety data for other patient populations, including pregnancy or breastfeeding, are not currently available. Expanded studies on more diverse populations should be conducted.…”

Section: Metabolism and Excretionmentioning

confidence: 90%

Edaravone Oral Suspension: A Neuroprotective Agent to Treat Amyotrophic Lateral Sclerosis

Singh,

Belliveau,

Towle

et al. 2024

American Journal of Therapeutics

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Background: Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons due to degeneration of nerve cells within the brain and spinal cord. Early symptoms include limb weakness, twitching or muscle cramping, and slurred speech. As the disease progresses, difficulty breathing, swallowing, and paralysis can lead to death. Currently, there are no medications that cure ALS, and guidelines recommend treatments focused on symptom management. Intravenous (IV) edaravone was approved by the US Food and Drug Administration (FDA) in 2017 as a treatment to slow the progression of ALS. In May 2022, the FDA approved an oral suspension (ORS) formulation of edaravone. Mechanism of Action: The mechanism of action of edaravone is not well defined. However, its neuroprotective effects are thought to result from antioxidant properties occurring through elimination of free radicals. Pharmacokinetics: Edaravone ORS (105 mg) has a bioavailability of 57% when compared with edaravone IV (60 mg). The ORS should be taken on an empty stomach in the morning, with water and no food or beverages, for 1 hour. Edaravone is bound to albumin (92%), has a mean volume of distribution of 63.1 L, a half-life of 4.5–9 hours, and a total clearance of 35.9 L/h after intravenous administration. Edaravone is metabolized into nonactive sulfate and glucuronide conjugates. Clinical Trials: The FDA approval was based on studies of the pharmacokinetics, safety, tolerability, and bioavailability of edaravone ORS. A phase III, global, multicenter, open-label safety study was conducted on edaravone ORS in 185 patients with ALS over 48 weeks. The most reported treatment-emergent adverse events were falls, muscular weakness, and constipation. Serious treatment-emergent adverse events included disease worsening, dysphagia, dyspnea, and respiratory failure. Therapeutic advance: Oral edaravone is an ALS treatment that can be self-administered or administered by a caregiver, precluding the need for administration by a health care professional in an institutional setting.

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“… 17 Population PK analyses also suggest nonlinearity in the clearance of IV edaravone and, within the IV dose range of 30 to 300 mg administered by infusion for 1 hour, an increase in exposures (area under the plasma concentration–time curve [AUC] and maximum plasma concentration [C max ]) greater than the dose ratio was observed in recent clinical studies. 18 , 19 , 20 …”

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confidence: 99%

Evaluation of Pharmacokinetics, Safety, and Drug‐Drug Interactions of an Oral Suspension of Edaravone in Healthy Adults

Shimizu¹,

Nishimura²,

Shiide³

et al. 2021

Clinical Pharm in Drug Dev

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Intravenous (IV) edaravone is approved as an amyotrophic lateral sclerosis (ALS) treatment. Because IV administration places a burden on patients, development of orally administered ALS treatments is needed. Therefore, 2 phase 1 studies of oral formulations of edaravone in healthy subjects examined the pharmacokinetics (PK), safety, racial differences, and drug‐drug interactions (DDIs) and investigated the dose of the oral formulation considered to be bioequivalent to the approved dose of the IV formulation. Study 1 was a placebo‐controlled, randomized, single‐blind study of single‐ascending‐dose oral edaravone with the dose range of 30 to 300 mg (n = 56). Study 2 was conducted in 2 cohorts (n = 84); the first assessed DDIs with multiple‐dose edaravone 120 mg/day given over 5 or 8 days (coadministered with single‐dose rosuvastatin, sildenafil, or furosemide), and the second evaluated PK and racial (Japanese/White) differences in PK parameters with doses of 100‐mg edaravone. The oral formulation of edaravone was well absorbed, and plasma concentrations of unchanged edaravone increased more than dose proportionally within the dose range of 30 to 300 mg. No effect of race on oral edaravone PK and no notable DDI effects possibly caused by orally administered edaravone were observed. The oral edaravone formulations were safe and tolerable under the assessed conditions. Mathematical modeling determined that equivalent exposures in plasma with the approved dose of the IV edaravone formulation, as reported previously, could be achieved when the oral edaravone formulation was administered at a dose of ≈100 mg, with an absolute bioavailability of ≈60%.

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An Open-label, Single-dose Study to Evaluate the Pharmacokinetic Variables of Edaravone in Subjects with Mild, Moderate, or No Renal Impairment

Cited by 4 publications

References 9 publications

Investigating Edaravone Use for Management of Amyotrophic Lateral Sclerosis (ALS): A Narrative Review

Investigating Edaravone Use for Management of Amyotrophic Lateral Sclerosis (ALS): A Narrative Review

Edaravone Oral Suspension: A Neuroprotective Agent to Treat Amyotrophic Lateral Sclerosis

Evaluation of Pharmacokinetics, Safety, and Drug‐Drug Interactions of an Oral Suspension of Edaravone in Healthy Adults

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