Peringatan Keamanan

LD50

The rat oral LD50 of donepezil is 32.6 mg/kg.L7928

Overdose information

Signs and symptoms of overdose with cholinesterase inhibitors such as donepezil can include severe nausea and vomiting, bradycardia, hypotension, perspiration, seizures, muscle weakness respiratory depression, and collapse. Significant muscle weakness may result in death if the respiratory muscles are affected by donepezil overdose. To manage an overdose, anticholinergics can be employed as antidotes. Atropine at intravenous doses of 1.0 - 2.0 mg can be administered and titrated according to the clinical response. Consult the local poison control center for the most updated guidelines on the management of a donepezil overdose. Whether donepezil can be removed from the body with dialysis is unknown at this time.L7916

Donepezil

DB00843

small molecule approved

Deskripsi

In 2016, the global burden of dementia was estimated to be 43.8 million, demonstrating a significant increase from a global prevalence of 20.2 million in 1990.A182411 Donepezil, also known as Aricept, is a piperidine derivative acetylcholinesterase inhibitor used in the management of the dementia of Alzheimer's Disease, and in some cases, is used to manage other types of dementia.

Donepezil was first approved by the FDA in 1996, and its extended-release form was approved in combination with Memantine in 2014 to manage moderate and severe forms of Alzheimer's dementia.L7916,L7937 A donepezil transdermal delivery system, Adlarity, was approved by the FDA in March 2022 for the treatment of Alzheimer's dementia.L41125 Though it does not alter the progression of Alzheimer's disease, donepezil is effective in managing the symptoms of its associated dementia.T668

Struktur Molekul 2D

Berat 379.492
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The average elimination half-life of donepezil is about 70 hours according to the results of various studies and the FDA label for donepezil.[A182333,L7916]. One pharmacokinetic study determined the average terminal half-life to be 81.5±22.0 h[A182324]
Volume Distribusi The volume of distribution of donepezil is 11.8 ± 1.7 L/kg for a 5-mg dose and 11.6 ± 1.91 L/kg for a 10-mg dose. It is largely distributed in the extravascular compartments. Donepezil crosses the blood-brain barrier and cerebrospinal fluid concentrations at the above doses have been measured at 15.7%.[A182333] The volume of distribution at steady-state according to the FDA label for donepezil ranges from 12 - 16 L/kg.[L7916]
Klirens (Clearance) According to the FDA label, the average apparent plasma clearance of this drug is 0.13 – 0.19 L/hr/kg.[L7916] A 5 mg dose of donepezil in healthy patients was shown to have a plasma clearance of 0.110±0.02 L/h/kg.[L7952] In 10 patients diagnosed with alcoholic cirrhosis, showed a mean decrease in clearance by 20% when compared to the clearance in 10 healthy subjects. In 4 patients with severe renal impairment compared to 4 healthy subjects, no significant change in clearance was noted.[L7952]

Absorpsi

Donepezil is slowly absorbed via the gastrointestinal tract after oral administration. Tmax is 3 to 4 hours with a bioavailability of 100% and steady-state concentrations are attained within 15 to 21 days of administration.A182333 The Tmax in one pharmacokinetic study determined a Tmax of 4.1 ± 1.5 hours.A182324 The Cmax of 5 mg donepezil tablets is estimated to be 8.34 ng/mL, according to the Canadian monograph.L7952 The AUC of 5 mg donepezil tablets has been determined to be 221.90-225.36 ng.hr/mL.L7952

Metabolisme

Donepezil is metabolized by first pass metabolism in the liver, primarily by CYP3A4, in addition to CYP2D6. After this, O-dealkylation, hydroxylation, N-oxidation, hydrolysis, and O-glucuronidation occur, producing various metabolites with similar half-lives to the unchanged parent drug. A study of the pharmacokinetics of radiolabeled donepezil demonstrated that about 53% of plasma radioactivity appeared as donepezil in the unchanged form, and 11% was identified as the metabolite 6-O-desmethyl donepezil, which exerts similar potency inhibition of the acetylcholinesterase enzyme.A182333,L7916 This drug is heavily metabolized to four primary metabolites, two of which are considered pharmacologically active, as well as to multiple inactive and unidentified metabolites.L7916

Rute Eliminasi

In a study of radiolabeled administration donepezil in healthy adults, 57% of measured radioactivity was identified in the urine, and 5% was identified in the feces.A182333

Farmakogenomik

1 Varian
CYP2D6 (rs1080985)

Patients with this genotype are have a decreased likelihood of responding to donepezil when treating Alzheimer's disease.

Interaksi Makanan

2 Data
  • 1. Avoid alcohol.
  • 2. Take with or without food. The absorption is unaffected by food.

Interaksi Obat

1383 Data
Ceritinib Donepezil may increase the bradycardic activities of Ceritinib.
Ivabradine Donepezil may increase the bradycardic activities of Ivabradine.
Ruxolitinib Ruxolitinib may increase the bradycardic activities of Donepezil.
Buprenorphine Donepezil may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
Doxylamine Doxylamine may increase the central nervous system depressant (CNS depressant) activities of Donepezil.
Dronabinol Dronabinol may increase the central nervous system depressant (CNS depressant) activities of Donepezil.
Droperidol Droperidol may increase the central nervous system depressant (CNS depressant) activities of Donepezil.
Hydrocodone Donepezil may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
Hydroxyzine Hydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Donepezil.
Magnesium sulfate The therapeutic efficacy of Donepezil can be increased when used in combination with Magnesium sulfate.
Metyrosine Donepezil may increase the sedative activities of Metyrosine.
Minocycline Minocycline may increase the central nervous system depressant (CNS depressant) activities of Donepezil.
Mirtazapine Donepezil may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
Nabilone Nabilone may increase the central nervous system depressant (CNS depressant) activities of Donepezil.
Paraldehyde Donepezil may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
Perampanel Perampanel may increase the central nervous system depressant (CNS depressant) activities of Donepezil.
Pramipexole Donepezil may increase the sedative activities of Pramipexole.
Ropinirole Donepezil may increase the sedative activities of Ropinirole.
Rotigotine Donepezil may increase the sedative activities of Rotigotine.
Rufinamide The risk or severity of adverse effects can be increased when Rufinamide is combined with Donepezil.
Sodium oxybate Donepezil may increase the central nervous system depressant (CNS depressant) activities of Sodium oxybate.
Suvorexant Donepezil may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
Tapentadol Tapentadol may increase the central nervous system depressant (CNS depressant) activities of Donepezil.
Thalidomide Donepezil may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
Zolpidem Donepezil may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Methadone The risk or severity of adverse effects can be increased when Methadone is combined with Donepezil.
Dipyridamole The therapeutic efficacy of Donepezil can be decreased when used in combination with Dipyridamole.
Ephedrine Donepezil may increase the neuromuscular blocking activities of Ephedrine.
Bambuterol Donepezil may increase the neuromuscular blocking activities of Bambuterol.
Sar9, Met (O2)11-Substance P Donepezil may increase the neuromuscular blocking activities of Sar9, Met (O2)11-Substance P.
Moxisylyte Donepezil may increase the neuromuscular blocking activities of Moxisylyte.
Propacetamol Donepezil may increase the neuromuscular blocking activities of Propacetamol.
Butyrylthiocholine Donepezil may increase the neuromuscular blocking activities of Butyrylthiocholine.
Oxybuprocaine Donepezil may increase the neuromuscular blocking activities of Oxybuprocaine.
Benzonatate Donepezil may increase the neuromuscular blocking activities of Benzonatate.
Succinylcholine The metabolism of Succinylcholine can be decreased when combined with Donepezil.
Mirabegron The serum concentration of Donepezil can be increased when it is combined with Mirabegron.
Ethanol Donepezil may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
Azelastine Donepezil may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
Brimonidine Brimonidine may increase the central nervous system depressant (CNS depressant) activities of Donepezil.
Sertraline The risk or severity of adverse effects can be increased when Donepezil is combined with Sertraline.
Sibutramine The risk or severity of adverse effects can be increased when Donepezil is combined with Sibutramine.
Zimelidine The risk or severity of adverse effects can be increased when Donepezil is combined with Zimelidine.
Dapoxetine The risk or severity of adverse effects can be increased when Donepezil is combined with Dapoxetine.
Milnacipran The risk or severity of adverse effects can be increased when Donepezil is combined with Milnacipran.
Desvenlafaxine The serum concentration of Donepezil can be increased when it is combined with Desvenlafaxine.
Seproxetine The risk or severity of adverse effects can be increased when Donepezil is combined with Seproxetine.
Indalpine The risk or severity of adverse effects can be increased when Donepezil is combined with Indalpine.
Alaproclate The risk or severity of adverse effects can be increased when Donepezil is combined with Alaproclate.
Citalopram The risk or severity of adverse effects can be increased when Donepezil is combined with Citalopram.
Trazodone The risk or severity of adverse effects can be increased when Donepezil is combined with Trazodone.
Esmolol Donepezil may increase the bradycardic activities of Esmolol.
Atenolol Donepezil may increase the bradycardic activities of Atenolol.
Timolol Donepezil may increase the bradycardic activities of Timolol.
Bisoprolol Donepezil may increase the bradycardic activities of Bisoprolol.
Carvedilol Donepezil may increase the bradycardic activities of Carvedilol.
Nadolol Donepezil may increase the bradycardic activities of Nadolol.
Bevantolol Donepezil may increase the bradycardic activities of Bevantolol.
Practolol Donepezil may increase the bradycardic activities of Practolol.
Dexpropranolol Donepezil may increase the bradycardic activities of Dexpropranolol.
Celiprolol Donepezil may increase the bradycardic activities of Celiprolol.
Nebivolol Donepezil may increase the bradycardic activities of Nebivolol.
Bufuralol Donepezil may increase the bradycardic activities of Bufuralol.
Bopindolol Donepezil may increase the bradycardic activities of Bopindolol.
Bupranolol Donepezil may increase the bradycardic activities of Bupranolol.
Arotinolol Donepezil may increase the bradycardic activities of Arotinolol.
Levobetaxolol Donepezil may increase the bradycardic activities of Levobetaxolol.
Talinolol Donepezil may increase the bradycardic activities of Talinolol.
Anisodamine Donepezil may increase the bradycardic activities of Anisodamine.
Bucindolol Donepezil may increase the bradycardic activities of Bucindolol.
Esatenolol Donepezil may increase the bradycardic activities of Esatenolol.
Cloranolol Donepezil may increase the bradycardic activities of Cloranolol.
Mepindolol Donepezil may increase the bradycardic activities of Mepindolol.
Epanolol Donepezil may increase the bradycardic activities of Epanolol.
Tertatolol Donepezil may increase the bradycardic activities of Tertatolol.
Betaxolol Donepezil may increase the bradycardic activities of Betaxolol.
Indenolol Donepezil may increase the bradycardic activities of Indenolol.
Propranolol Donepezil may increase the bradycardic activities of Propranolol.
Landiolol Donepezil may increase the bradycardic activities of Landiolol.
Flupentixol The risk or severity of CNS depression can be increased when Donepezil is combined with Flupentixol.
Zopiclone The risk or severity of adverse effects can be increased when Donepezil is combined with Zopiclone.
Bendroflumethiazide Bendroflumethiazide may increase the bradycardic activities of Donepezil.
Methyldopa Donepezil may increase the bradycardic activities of Methyldopa.
Rivastigmine Donepezil may increase the bradycardic activities of Rivastigmine.
Lucinactant Donepezil may increase the bradycardic activities of Lucinactant.
Calfactant Donepezil may increase the bradycardic activities of Calfactant.
Beractant Donepezil may increase the bradycardic activities of Beractant.
Lanreotide Donepezil may increase the bradycardic activities of Lanreotide.
Poractant alfa Donepezil may increase the bradycardic activities of Poractant alfa.
Midodrine Midodrine may increase the bradycardic activities of Donepezil.
Bretylium Donepezil may increase the bradycardic activities of Bretylium.
Fingolimod Donepezil may increase the bradycardic activities of Fingolimod.
Cinnarizine Cinnarizine may increase the bradycardic activities of Donepezil.
Galantamine Galantamine may increase the bradycardic activities of Donepezil.
Levomenthol Levomenthol may increase the bradycardic activities of Donepezil.
Nimesulide Donepezil may increase the bradycardic activities of Nimesulide.
Prenylamine Donepezil may increase the bradycardic activities of Prenylamine.
Cyclandelate Donepezil may increase the bradycardic activities of Cyclandelate.
Seletracetam Donepezil may increase the bradycardic activities of Seletracetam.
Nylidrin Donepezil may increase the bradycardic activities of Nylidrin.

Target Protein

Acetylcholinesterase ACHE
5-hydroxytryptamine receptor 2A HTR2A
Cholinesterase BCHE
Nitric oxide synthase 1 NOS1
Tumor necrosis factor-inducible gene 6 protein TNFAIP6
Interleukin-1 beta IL1B
Nuclear factor NF-kappa-B NFKB2
NMDA receptor GRIN1

Referensi & Sumber

Synthesis reference: Akio Imai, Hideaki Watanabe, Takashi Kajima, Yasushi Ishihama, Akiyo Ohtsuka, Tomohide Tanaka, Yukio Narabu, "Polymorphs of donepezil hydrochloride and process for production." U.S. Patent US5985864, issued December, 1988.
Artikel (PubMed)
  • PMID: 15948662
    Xiong G, Doraiswamy PM: Combination drug therapy for Alzheimer's disease: what is evidence-based, and what is not? Geriatrics. 2005 Jun;60(6):22-6.
  • PMID: 12105320
    Yesavage JA, Mumenthaler MS, Taylor JL, Friedman L, O'Hara R, Sheikh J, Tinklenberg J, Whitehouse PJ: Donepezil and flight simulator performance: effects on retention of complex skills. Neurology. 2002 Jul 9;59(1):123-5.
  • PMID: 11893059
    Sugimoto H: Donepezil hydrochloride: a treatment drug for Alzheimer's disease. Chem Rec. 2001;1(1):63-73.
  • PMID: 29768996
    Korabecny J, Spilovska K, Mezeiova E, Benek O, Juza R, Kaping D, Soukup O: A systematic review on donepezil-based derivatives as potential cholinesterase inhibitors for Alzheimer's disease. Curr Med Chem. 2018 May 16. pii: CMC-EPUB-90497. doi: 10.2174/0929867325666180517094023.
  • PMID: 24785550
    Prvulovic D, Schneider B: Pharmacokinetic and pharmacodynamic evaluation of donepezil for the treatment of Alzheimer's disease. Expert Opin Drug Metab Toxicol. 2014 Jul;10(7):1039-50. doi: 10.1517/17425255.2014.915028. Epub 2014 Apr 30.
  • PMID: 9839758
    Rogers SL, Friedhoff LT: Pharmacokinetic and pharmacodynamic profile of donepezil HCl following single oral doses. Br J Clin Pharmacol. 1998 Nov;46 Suppl 1:1-6. doi: 10.1046/j.1365-2125.1998.0460s1001.x.
  • PMID: 9839761
    Tiseo PJ, Perdomo CA, Friedhoff LT: Metabolism and elimination of 14C-donepezil in healthy volunteers: a single-dose study. Br J Clin Pharmacol. 1998 Nov;46 Suppl 1:19-24. doi: 10.1046/j.1365-2125.1998.0460s1019.x.
  • PMID: 16863459
    Seltzer B: Donepezil: a review. Expert Opin Drug Metab Toxicol. 2005 Oct;1(3):527-36. doi: 10.1517/17425255.1.3.527 .
Menampilkan 8 dari 17 artikel.
Textbook
  • Anil Kumar; Sandeep Sharma (2019). Donepezil. Stat Pearls.

Contoh Produk & Brand

Produk: 359 • International brands: 15
Produk
  • Accel-donepezil
    Tablet • 5 mg • Oral • Canada • Generic • Approved
  • Accel-donepezil
    Tablet • 10 mg • Oral • Canada • Generic • Approved
  • Ach-donepezil
    Tablet • 5 mg • Oral • Canada • Generic • Approved
  • Ach-donepezil
    Tablet • 10 mg • Oral • Canada • Generic • Approved
  • Act Donepezil
    Tablet • 5 mg • Oral • Canada • Approved
  • Act Donepezil
    Tablet • 10 mg • Oral • Canada • Approved
  • Act Donepezil ODT
    Tablet, orally disintegrating • 5 mg • Oral • Canada • Approved
  • Act Donepezil ODT
    Tablet, orally disintegrating • 10 mg • Oral • Canada • Approved
Menampilkan 8 dari 359 produk.
International Brands
  • Alzepil — Egis
  • Davia — Terapia
  • Depzil — Psyco Remedies
  • Donecept — Actavis
  • Donecil — ABL Pharma
  • Donep — Alkem
  • Donepex — Schafer
  • Donesyn — Synthon
  • Dopezil — Medis
  • Eranz — Wyeth

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