Peringatan Keamanan

The oral LD50 in mice is >300mg/kg.L8216

Patients experiencing an overdose may present with hallucinations, agitation, and dyskinesia.L8237 Treat patients by discontinuing istradefylline and administering supportive treatment.L8237

Istradefylline

DB11757

small molecule approved investigational

Deskripsi

Istradefylline, or KW6002, was developed by Kyowa Hakko Kirin in Japan for the treatment of Parkinson's disease as an adjunct to standard therapy.A184067 Unlike standard dopaminergic therapies for Parkinson's, Istradefylline targets adenosine A2A receptors in the basal ganglia.A184067 This region of the brain is highly involved in motor control.A184067

Istradefylline is indicated as an adjunct treatment to levodopa and carbidopa for Parkinson's disease.L8237

This drug was first approved in Japan on 25 March 2013.A184067 Istradefylline was granted FDA approval on 27 August 2019.L8213

Struktur Molekul 2D

Berat 384.436
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The terminal elimination half life of istradefylline was 64-69 hours.[A184064,A184067]
Volume Distribusi The apparent volume of distribution of istradefylline is 448-557L.[A184064]
Klirens (Clearance) The apparent clearance of istradefylline is 4.1-6.0L/h.[A184064]

Absorpsi

Istradefylline reaches a Cmax of 181.1ng/mL with a Tmax of 2.0h and an AUC of 11,100ng\*h/mL.A184064 M1, the primary active metabolite, reaches a Cmax of 4.34ng/mL with a Tmax of 3.5h.A184064 The M8 metabolite reaches a Cmax of 12.6ng/mL with a Tmax of 3.0h and an AUC of 610ng\*h/mL.A184064

Metabolisme

The primary metabolite found in urine is the active 4'-O-monodesmethyl istradefylline (M1).A184064 Istradefylline is metabolized mainly by CYP1A1, CYP3A4, and CYP3A5.A184064 CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C18, and CYP2D6 also partly contribute the the metabolism of istradefylline.A184064 Other identified metabolites are 1-?-hydroxylated-4’-O-demethyl istradefylline (M2), 3’,4’-O-didemethyl istradefylline (M3), M1 sulfate conjugate (M4), M1 glucuronide (M5), 1-?-hydroxylated istradefylline (M8) and hydrogenated M3 (M10).L8225

Rute Eliminasi

A 3mg/kg oral dose given to male rats was 17.6% elminated in the urine and 68.3% eliminated in the feces.L8225 In urine, 5.31% of the total dose was the M3 metabolite and 1.96% of the total dose was the M1 metabolite.L8225 In feces, 30.60% of the total dose was the M3 metabolite, 9.34% of the total dose was the M1 metabolite, 8.33% of the total dose was the M10 metabolite, and 1.62% of the total dose was unchanged istradefylline.L8225

Interaksi Makanan

3 Data
  • 1. Avoid St. John's Wort. St. John's Wort decreases istradefylline concentrations.
  • 2. Take at the same time every day.
  • 3. Take with or without food.

Interaksi Obat

1083 Data
Afatinib The serum concentration of Afatinib can be increased when it is combined with Istradefylline.
Bosutinib The serum concentration of Bosutinib can be increased when it is combined with Istradefylline.
Brentuximab vedotin The serum concentration of Brentuximab vedotin can be increased when it is combined with Istradefylline.
Colchicine The serum concentration of Colchicine can be increased when it is combined with Istradefylline.
Edoxaban The serum concentration of Edoxaban can be increased when it is combined with Istradefylline.
Ledipasvir The serum concentration of Ledipasvir can be increased when it is combined with Istradefylline.
Naloxegol The serum concentration of Naloxegol can be increased when it is combined with Istradefylline.
Pazopanib The serum concentration of Pazopanib can be increased when it is combined with Istradefylline.
Prucalopride The serum concentration of Prucalopride can be increased when it is combined with Istradefylline.
Ranolazine The serum concentration of Ranolazine can be increased when it is combined with Istradefylline.
Silodosin The excretion of Silodosin can be decreased when combined with Istradefylline.
Topotecan The serum concentration of Topotecan can be increased when it is combined with Istradefylline.
Deferasirox The serum concentration of Istradefylline can be increased when it is combined with Deferasirox.
Peginterferon alfa-2b The serum concentration of Istradefylline can be increased when it is combined with Peginterferon alfa-2b.
Leflunomide The serum concentration of Istradefylline can be decreased when it is combined with Leflunomide.
Teriflunomide The serum concentration of Istradefylline can be decreased when it is combined with Teriflunomide.
Everolimus The serum concentration of Everolimus can be increased when it is combined with Istradefylline.
Rifaximin The serum concentration of Rifaximin can be increased when it is combined with Istradefylline.
Mifepristone The serum concentration of Istradefylline can be increased when it is combined with Mifepristone.
Mirabegron The serum concentration of Istradefylline can be increased when it is combined with Mirabegron.
Abiraterone The serum concentration of Istradefylline can be increased when it is combined with Abiraterone.
Eluxadoline The serum concentration of Eluxadoline can be increased when it is combined with Istradefylline.
Vincristine The excretion of Vincristine can be decreased when combined with Istradefylline.
Cyproterone acetate The metabolism of Istradefylline can be increased when combined with Cyproterone acetate.
Doxorubicin The serum concentration of Doxorubicin can be increased when it is combined with Istradefylline.
Primidone The metabolism of Istradefylline can be increased when combined with Primidone.
Albendazole The metabolism of Istradefylline can be increased when combined with Albendazole.
Caffeine The metabolism of Istradefylline can be decreased when combined with Caffeine.
Moxifloxacin The metabolism of Istradefylline can be decreased when combined with Moxifloxacin.
Lidocaine The metabolism of Istradefylline can be decreased when combined with Lidocaine.
Mexiletine The metabolism of Istradefylline can be decreased when combined with Mexiletine.
Alosetron The metabolism of Istradefylline can be decreased when combined with Alosetron.
Gatifloxacin The metabolism of Istradefylline can be decreased when combined with Gatifloxacin.
Simeprevir The metabolism of Istradefylline can be decreased when combined with Simeprevir.
Lobeglitazone The metabolism of Istradefylline can be decreased when combined with Lobeglitazone.
Pazufloxacin The metabolism of Istradefylline can be decreased when combined with Pazufloxacin.
Osilodrostat The metabolism of Istradefylline can be decreased when combined with Osilodrostat.
Imipramine The metabolism of Istradefylline can be decreased when combined with Imipramine.
Dosulepin The metabolism of Istradefylline can be decreased when combined with Dosulepin.
Cyclosporine The metabolism of Istradefylline can be decreased when combined with Cyclosporine.
Cholecalciferol The metabolism of Istradefylline can be decreased when combined with Cholecalciferol.
Fluvoxamine The metabolism of Istradefylline can be decreased when combined with Fluvoxamine.
Metoprolol The metabolism of Istradefylline can be decreased when combined with Metoprolol.
Venlafaxine The metabolism of Istradefylline can be decreased when combined with Venlafaxine.
Clobazam The serum concentration of Istradefylline can be increased when it is combined with Clobazam.
Clozapine The serum concentration of Istradefylline can be increased when it is combined with Clozapine.
Quinine The metabolism of Istradefylline can be decreased when combined with Quinine.
Duloxetine The metabolism of Istradefylline can be decreased when combined with Duloxetine.
Chlorpromazine The therapeutic efficacy of Istradefylline can be decreased when used in combination with Chlorpromazine.
Celecoxib The metabolism of Istradefylline can be decreased when combined with Celecoxib.
Darifenacin The metabolism of Istradefylline can be decreased when combined with Darifenacin.
Cimetidine The metabolism of Istradefylline can be decreased when combined with Cimetidine.
Chloroquine The metabolism of Istradefylline can be decreased when combined with Chloroquine.
Nicardipine The metabolism of Istradefylline can be decreased when combined with Nicardipine.
Tranylcypromine The metabolism of Istradefylline can be decreased when combined with Tranylcypromine.
Terbinafine The metabolism of Istradefylline can be decreased when combined with Terbinafine.
Perhexiline The metabolism of Istradefylline can be decreased when combined with Perhexiline.
Tegaserod The metabolism of Istradefylline can be decreased when combined with Tegaserod.
Primaquine The metabolism of Istradefylline can be decreased when combined with Primaquine.
Desipramine The metabolism of Istradefylline can be decreased when combined with Desipramine.
Fusidic acid The metabolism of Istradefylline can be decreased when combined with Fusidic acid.
Panobinostat The metabolism of Istradefylline can be decreased when combined with Panobinostat.
Vilazodone The metabolism of Istradefylline can be decreased when combined with Vilazodone.
Lumefantrine The metabolism of Istradefylline can be decreased when combined with Lumefantrine.
Sulfaphenazole The metabolism of Istradefylline can be decreased when combined with Sulfaphenazole.
Phenylbutyric acid The metabolism of Istradefylline can be decreased when combined with Phenylbutyric acid.
Manidipine The metabolism of Istradefylline can be decreased when combined with Manidipine.
Rolapitant The metabolism of Istradefylline can be decreased when combined with Rolapitant.
Asunaprevir The metabolism of Istradefylline can be decreased when combined with Asunaprevir.
Rucaparib The metabolism of Istradefylline can be decreased when combined with Rucaparib.
Ritanserin The metabolism of Istradefylline can be decreased when combined with Ritanserin.
Rhein The metabolism of Istradefylline can be decreased when combined with Rhein.
Lorcaserin The metabolism of Istradefylline can be decreased when combined with Lorcaserin.
Thioridazine The therapeutic efficacy of Istradefylline can be decreased when used in combination with Thioridazine.
Paroxetine The metabolism of Istradefylline can be decreased when combined with Paroxetine.
Cinacalcet The metabolism of Istradefylline can be decreased when combined with Cinacalcet.
Bupropion The risk or severity of adverse effects can be increased when Bupropion is combined with Istradefylline.
Orphenadrine The metabolism of Istradefylline can be decreased when combined with Orphenadrine.
Propafenone The metabolism of Istradefylline can be decreased when combined with Propafenone.
Halofantrine The metabolism of Istradefylline can be decreased when combined with Halofantrine.
Methotrimeprazine The therapeutic efficacy of Istradefylline can be decreased when used in combination with Methotrimeprazine.
Glycerol phenylbutyrate The metabolism of Istradefylline can be decreased when combined with Glycerol phenylbutyrate.
Cisapride The metabolism of Istradefylline can be decreased when combined with Cisapride.
Troglitazone The metabolism of Istradefylline can be decreased when combined with Troglitazone.
Nabilone The metabolism of Istradefylline can be decreased when combined with Nabilone.
Imatinib The serum concentration of Istradefylline can be increased when it is combined with Imatinib.
Felbamate The metabolism of Istradefylline can be decreased when combined with Felbamate.
Sulfinpyrazone The metabolism of Istradefylline can be decreased when combined with Sulfinpyrazone.
Iproniazid The metabolism of Istradefylline can be decreased when combined with Iproniazid.
Medical Cannabis The metabolism of Istradefylline can be decreased when combined with Medical Cannabis.
Valproic acid The metabolism of Istradefylline can be decreased when combined with Valproic acid.
Miconazole The metabolism of Istradefylline can be decreased when combined with Miconazole.
Fluconazole The metabolism of Istradefylline can be decreased when combined with Fluconazole.
Floxuridine The metabolism of Istradefylline can be decreased when combined with Floxuridine.
Gemfibrozil The metabolism of Istradefylline can be decreased when combined with Gemfibrozil.
Secobarbital The metabolism of Istradefylline can be increased when combined with Secobarbital.
Bexarotene The metabolism of Istradefylline can be decreased when combined with Bexarotene.
Diltiazem The metabolism of Istradefylline can be decreased when combined with Diltiazem.
Loratadine The metabolism of Istradefylline can be decreased when combined with Loratadine.
Medroxyprogesterone acetate The metabolism of Istradefylline can be decreased when combined with Medroxyprogesterone acetate.

Target Protein

Adenosine receptor A2a ADORA2A
Adenosine receptor A1 ADORA1

Referensi & Sumber

Synthesis reference: https://patents.google.com/patent/CN104974157A/en
Artikel (PubMed)
  • PMID: 28881378
    Mukai M, Uchimura T, Zhang X, Greene D, Vergeire M, Cantillon M: Effects of Rifampin on the Pharmacokinetics of a Single Dose of Istradefylline in Healthy Subjects. J Clin Pharmacol. 2018 Feb;58(2):193-201. doi: 10.1002/jcph.1003. Epub 2017 Sep 7.
  • PMID: 23700273
    Dungo R, Deeks ED: Istradefylline: first global approval. Drugs. 2013 Jun;73(8):875-82. doi: 10.1007/s40265-013-0066-7.
  • PMID: 30281377
    Takahashi M, Fujita M, Asai N, Saki M, Mori A: Safety and effectiveness of istradefylline in patients with Parkinson's disease: interim analysis of a post-marketing surveillance study in Japan. Expert Opin Pharmacother. 2018 Oct;19(15):1635-1642. doi: 10.1080/14656566.2018.1518433. Epub 2018 Oct 3.
  • PMID: 25768849
    Kondo T, Mizuno Y: A long-term study of istradefylline safety and efficacy in patients with Parkinson disease. Clin Neuropharmacol. 2015 Mar-Apr;38(2):41-6. doi: 10.1097/WNF.0000000000000073.

Contoh Produk & Brand

Produk: 2 • International brands: 1
Produk
  • Nourianz
    Tablet, film coated • 20 mg/1 • Oral • US • Approved
  • Nourianz
    Tablet, film coated • 40 mg/1 • Oral • US • Approved
International Brands
  • Nouriast

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