Bioavailability and Pharmacokinetics of Once-Daily Amantadine Extended-Release Tablets in Healthy Volunteers: Results from Three Randomized, Crossover, Open-Label, Phase 1 Studies

deVries, Tina; Dentiste, Angela; Handiwala, Lata; Jacobs, David E.

doi:10.1007/s40120-019-0144-1

Cited by 16 publications

(16 citation statements)

References 11 publications

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“…The PK profile of the drug makes it particularly. Amantadine HCl IR is available as a 100-mg tablet (equivalent to 81 mg base amantadine) and 50 mg/5 mL syrup (equivalent to 40 mg/5 mL base amantadine), and is typically administered twice daily 16 .…”

Section: Drug Screenmentioning

confidence: 99%

“Amantadine disrupts lysosomal gene expression; potential therapy for COVID19”

Smieszek

Przychodzen

Polymeropoulos

2020

Preprint

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SARS-coronavirus 2 is the causal agent of the COVID-19 outbreak. SARS-Cov-2 entry into a cell is dependent upon binding of the viral spike (S) protein to cellular receptor and on cleavage of the spike protein by the host cell proteases such as Cathepsin L and Cathepsin B. CTSL/B are crucial elements of lysosomal pathway and both enzymes are almost exclusively located in the lysosomes.CTSL disruption offers potential for CoVID-19 therapies. The mechanisms of disruption include: decreasing expression of CTSL, direct inhibition of CTSL activity and affecting the conditions of CTSL environment (increase pH in lysosomes).We have conducted a high throughput drug screen gene expression analysis to identify compounds that would downregulate the expression of CTSL/CTSB. One of the top significant results shown to downregulate the expression of the CTSL gene is Amantadine. Amantadine was approved by the US Food and Drug Administration in 1968 as a prophylactic agent for influenza and later for Parkinson's disease. It is available as a generic drug.. Amantadine in addition to downregulating CTSL appears to further disrupt lysosomal pathway , hence interfering with the capacity of the virus to replicate. It acts as a lysosomotropic agent altering the CTSL functional environment. We hypothesize that Amantadine could decrease the viral load in SARS-CoV-2 positive patients and as such it may serve as a potent therapeutic decreasing the replication and infectivity of the virus likely leading to better clinical outcomes. Clinical studies will be needed to examine the therapeutic utility of amantadine in COVID-19 infection.was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

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Section: Drug Screenmentioning

confidence: 99%

“Amantadine disrupts lysosomal gene expression; potential therapy for COVID19”

Smieszek

Przychodzen

Polymeropoulos

2020

Preprint

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“…Plasma half-life is 17 hours (range: 10 to 25 hours) with renal clearance as main elimination mechanism. Amantadine HCl immediate release is available as a 100-mg tablet and 50 mg/5 mL syrup and is typically administered twice daily [18] . Human cells in tissue culture readily tolerated amantadine up to a concentration of 100 ug/mL (~657uM).…”

Section: Drugs Screeningmentioning

confidence: 99%

Amantadine disrupts lysosomal gene expression: A hypothesis for COVID19 treatment

Smieszek

Przychodzen

Polymeropoulos

2020

International Journal of Antimicrobial Agents

108

105

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Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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“…ER 129, p.o. IR (BID) Pharmacokinetics extended release vs. immediate release 1.74 (p) 2.45 (p) 3.35 (p) 2.15 (p) deVries et al ( 2019 ) 50–300, p.o. 78 Parkinsonian patients 5.3 (average p) Nishikawa et al ( 2009 ) 200, p.o.…”

Section: Amantadine Therapeutic Concentrations (Animal and Human Datamentioning

confidence: 99%

Amantadine: reappraisal of the timeless diamond—target updates and novel therapeutic potentials

et al. 2021

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The aim of the current review was to provide a new, in-depth insight into possible pharmacological targets of amantadine to pave the way to extending its therapeutic use to further indications beyond Parkinson’s disease symptoms and viral infections. Considering amantadine’s affinities in vitro and the expected concentration at targets at therapeutic doses in humans, the following primary targets seem to be most plausible: aromatic amino acids decarboxylase, glial-cell derived neurotrophic factor, sigma-1 receptors, phosphodiesterases, and nicotinic receptors. Further three targets could play a role to a lesser extent: NMDA receptors, 5-HT3 receptors, and potassium channels. Based on published clinical studies, traumatic brain injury, fatigue [e.g., in multiple sclerosis (MS)], and chorea in Huntington’s disease should be regarded potential, encouraging indications. Preclinical investigations suggest amantadine’s therapeutic potential in several further indications such as: depression, recovery after spinal cord injury, neuroprotection in MS, and cutaneous pain. Query in the database http://www.clinicaltrials.gov reveals research interest in several further indications: cancer, autism, cocaine abuse, MS, diabetes, attention deficit-hyperactivity disorder, obesity, and schizophrenia.

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Bioavailability and Pharmacokinetics of Once-Daily Amantadine Extended-Release Tablets in Healthy Volunteers: Results from Three Randomized, Crossover, Open-Label, Phase 1 Studies

Cited by 16 publications

References 11 publications

“Amantadine disrupts lysosomal gene expression; potential therapy for COVID19”

“Amantadine disrupts lysosomal gene expression; potential therapy for COVID19”

Amantadine disrupts lysosomal gene expression: A hypothesis for COVID19 treatment

Amantadine: reappraisal of the timeless diamond—target updates and novel therapeutic potentials

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