Peringatan Keamanan

The LD50 information and overdose information is unavailable at this time. Current clinical study results suggest that dose-limiting toxicities of voxelotor are unlikely.A188126

Voxelotor

DB14975

small molecule approved investigational

Deskripsi

Voxelotor is a novel hemoglobin S polymerization inhibitor for the treatment of sickle cell disease. This is a genetically inherited condition most prevalent in the Middle East, Africa, and certain parts of India. Sickle cell disease can lead to excruciating pain, stroke, infection, and various other complications arising from the blockage of blood vessels.T734

Voxelotor was granted accelerated FDA approval on November 25 2019, as it is likely to be a promising treatment for the 100,000 individuals in the U.S. suffering from the disease, in addition to 20 million others worldwide.L10403 It was developed by Global Blood Therapeutics, Inc.L10403 and is unique from other drugs used to treat sickle cell anemia, such as hydroxyurea, L-glutamine, and crizanlizumabA188135,A188138 due to its novel mechanism of action. The EMA approved the use of voxelotor for the treatment of hemolytic anemia associated with sickle cell disease in February 2022.L41419,L41424

Struktur Molekul 2D

Berat 337.379
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The plasma elimination half-life of voxelotor in sickle cell disease patients is about 35.5 hours.[L10397] The mean half-life in the red blood cell is 60 days. In one study, the average plasma half-life of voxelotor was 50 hours in patients with sickle cell disease, compared with 61–85 hours in healthy subjects.[A188126]
Volume Distribusi The apparent volume of distribution of voxelotor in the central compartment is 338L and 72.2L in the plasma.[L10397]
Klirens (Clearance) The apparent oral clearance of voxelotor is approximately 6.7 L/h.[L10397]

Absorpsi

Voxelotor is rapidly absorbed after oral administration, with a plasma Tmax of 2 hours.A188126,L10406 Tmax in the red blood cells ranges from 17-24 hours.A188126 The Cmax in whole blood and red blood cells occur 6 and 18 hours after an oral dose, respectively. Consumption of a high-fat meal with voxelotor significantly increased exposure to the drug during clinical trials.L10397 After a daily dose of either 300, 600, or 900 mg for a period of 15 days, when steady-state concentrations were reached, the average RBC Cmax for the respective doses were measured to be 4950, 9610 and 14 000 ?g*h mL?1, respectively.A188126

Metabolisme

Voxeletor is heavily metabolized via two phases. Phase I metabolism consists of oxidation and reduction, while phase II metabolism consists of glucuronidation. Voseletor is oxidized mainly by CYP3A4 and by CYP2C19, CYP2B6, and CYP2C9, to a lesser extent.L10397,L10406

Rute Eliminasi

About 62.6% of the oral dose is found in the feces, of which 33.3% is an unchanged drug. About 35.5% of the dose is recovered in urine, with only 0.08% as the unchanged drug.A188126,L10397,L10406

Interaksi Makanan

3 Data
  • 1. Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of voxelotor.
  • 2. Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of voxelotor.
  • 3. Take with or without food.

Interaksi Obat

645 Data
Lumacaftor The serum concentration of Voxelotor can be decreased when it is combined with Lumacaftor.
Ticlopidine The metabolism of Voxelotor can be decreased when combined with Ticlopidine.
Gemfibrozil The metabolism of Voxelotor can be decreased when combined with Gemfibrozil.
Imipramine The metabolism of Voxelotor can be decreased when combined with Imipramine.
Fluoxetine The metabolism of Voxelotor can be decreased when combined with Fluoxetine.
Eslicarbazepine acetate The metabolism of Voxelotor can be decreased when combined with Eslicarbazepine acetate.
Troglitazone The metabolism of Voxelotor can be decreased when combined with Troglitazone.
Nabilone The metabolism of Voxelotor can be decreased when combined with Nabilone.
Felbamate The metabolism of Voxelotor can be decreased when combined with Felbamate.
Sulfinpyrazone The metabolism of Voxelotor can be decreased when combined with Sulfinpyrazone.
Iproniazid The metabolism of Voxelotor can be decreased when combined with Iproniazid.
Medical Cannabis The metabolism of Voxelotor can be decreased when combined with Medical Cannabis.
Floxuridine The metabolism of Voxelotor can be decreased when combined with Floxuridine.
Sulfaphenazole The metabolism of Voxelotor can be decreased when combined with Sulfaphenazole.
Apalutamide The serum concentration of Voxelotor can be increased when it is combined with Apalutamide.
Pitolisant The serum concentration of Voxelotor can be decreased when it is combined with Pitolisant.
Metreleptin The metabolism of Voxelotor can be increased when combined with Metreleptin.
Pantoprazole The metabolism of Voxelotor can be decreased when combined with Pantoprazole.
Olanzapine The metabolism of Voxelotor can be decreased when combined with Olanzapine.
Nilutamide The metabolism of Voxelotor can be decreased when combined with Nilutamide.
Esomeprazole The metabolism of Voxelotor can be decreased when combined with Esomeprazole.
Zonisamide The metabolism of Voxelotor can be decreased when combined with Zonisamide.
Oritavancin The metabolism of Voxelotor can be decreased when combined with Oritavancin.
Dexlansoprazole The metabolism of Voxelotor can be decreased when combined with Dexlansoprazole.
Artenimol The metabolism of Voxelotor can be decreased when combined with Artenimol.
Sildenafil The metabolism of Voxelotor can be decreased when combined with Sildenafil.
Ethambutol The metabolism of Voxelotor can be decreased when combined with Ethambutol.
Mephenytoin The metabolism of Voxelotor can be decreased when combined with Mephenytoin.
Telmisartan The metabolism of Voxelotor can be decreased when combined with Telmisartan.
Ethinylestradiol The metabolism of Voxelotor can be decreased when combined with Ethinylestradiol.
Moclobemide The metabolism of Voxelotor can be decreased when combined with Moclobemide.
Methsuximide The metabolism of Voxelotor can be decreased when combined with Methsuximide.
Gestodene The metabolism of Voxelotor can be decreased when combined with Gestodene.
Lobeglitazone The metabolism of Voxelotor can be decreased when combined with Lobeglitazone.
Benzbromarone The metabolism of Voxelotor can be decreased when combined with Benzbromarone.
Eslicarbazepine The metabolism of Voxelotor can be decreased when combined with Eslicarbazepine.
Curcumin sulfate The metabolism of Voxelotor can be decreased when combined with Curcumin sulfate.
Topiramate The metabolism of Voxelotor can be decreased when combined with Topiramate.
Letrozole The metabolism of Voxelotor can be decreased when combined with Letrozole.
Somapacitan The metabolism of Voxelotor can be decreased when combined with Somapacitan.
Rifapentine The serum concentration of Voxelotor can be decreased when it is combined with Rifapentine.
Rifabutin The metabolism of Voxelotor can be increased when combined with Rifabutin.
Trimethadione The metabolism of Voxelotor can be decreased when combined with Trimethadione.
Clobazam The metabolism of Voxelotor can be decreased when combined with Clobazam.
Timolol The metabolism of Voxelotor can be decreased when combined with Timolol.
Carisoprodol The metabolism of Voxelotor can be decreased when combined with Carisoprodol.
Albendazole The metabolism of Voxelotor can be decreased when combined with Albendazole.
Doxazosin The metabolism of Voxelotor can be decreased when combined with Doxazosin.
Thioridazine The metabolism of Voxelotor can be decreased when combined with Thioridazine.
Clopidogrel The metabolism of Voxelotor can be decreased when combined with Clopidogrel.
Estradiol The metabolism of Voxelotor can be decreased when combined with Estradiol.
Methylphenobarbital The metabolism of Voxelotor can be decreased when combined with Methylphenobarbital.
Ramelteon The metabolism of Voxelotor can be decreased when combined with Ramelteon.
Praziquantel The metabolism of Voxelotor can be decreased when combined with Praziquantel.
Proguanil The metabolism of Voxelotor can be decreased when combined with Proguanil.
Escitalopram The metabolism of Voxelotor can be decreased when combined with Escitalopram.
Hexobarbital The metabolism of Voxelotor can be decreased when combined with Hexobarbital.
Barbital The metabolism of Voxelotor can be decreased when combined with Barbital.
Lacosamide The metabolism of Voxelotor can be decreased when combined with Lacosamide.
Apixaban The metabolism of Voxelotor can be decreased when combined with Apixaban.
Artemether The metabolism of Voxelotor can be decreased when combined with Artemether.
Seratrodast The metabolism of Voxelotor can be decreased when combined with Seratrodast.
(R)-warfarin The metabolism of Voxelotor can be decreased when combined with (R)-warfarin.
Vortioxetine The metabolism of Voxelotor can be decreased when combined with Vortioxetine.
Etizolam The metabolism of Voxelotor can be decreased when combined with Etizolam.
Fedratinib The serum concentration of Voxelotor can be increased when it is combined with Fedratinib.
Dexrabeprazole The metabolism of Voxelotor can be decreased when combined with Dexrabeprazole.
(S)-Warfarin The metabolism of Voxelotor can be decreased when combined with (S)-Warfarin.
Testosterone The metabolism of Voxelotor can be decreased when combined with Testosterone.
Formoterol The metabolism of Voxelotor can be decreased when combined with Formoterol.
Gliclazide The metabolism of Voxelotor can be decreased when combined with Gliclazide.
Propranolol The metabolism of Voxelotor can be decreased when combined with Propranolol.
Labetalol The metabolism of Voxelotor can be decreased when combined with Labetalol.
Nebivolol The metabolism of Voxelotor can be decreased when combined with Nebivolol.
Vilazodone The metabolism of Voxelotor can be decreased when combined with Vilazodone.
Zolpidem The metabolism of Voxelotor can be decreased when combined with Zolpidem.
Doxepin The metabolism of Voxelotor can be decreased when combined with Doxepin.
Selumetinib The metabolism of Voxelotor can be decreased when combined with Selumetinib.
Esketamine The metabolism of Voxelotor can be decreased when combined with Esketamine.
Pentamidine The metabolism of Voxelotor can be decreased when combined with Pentamidine.
Lynestrenol The metabolism of Voxelotor can be decreased when combined with Lynestrenol.
Progesterone The metabolism of Voxelotor can be decreased when combined with Progesterone.
Benzocaine The metabolism of Voxelotor can be decreased when combined with Benzocaine.
Memantine The metabolism of Voxelotor can be decreased when combined with Memantine.
Nevirapine The metabolism of Voxelotor can be increased when combined with Nevirapine.
Nicotine The metabolism of Voxelotor can be decreased when combined with Nicotine.
Tramadol The metabolism of Voxelotor can be decreased when combined with Tramadol.
Mexiletine The metabolism of Voxelotor can be decreased when combined with Mexiletine.
Cinnarizine The metabolism of Voxelotor can be decreased when combined with Cinnarizine.
Diclofenac The metabolism of Voxelotor can be decreased when combined with Diclofenac.
Isoflurane The metabolism of Voxelotor can be decreased when combined with Isoflurane.
Brompheniramine The metabolism of Voxelotor can be decreased when combined with Brompheniramine.
Benzphetamine The metabolism of Voxelotor can be decreased when combined with Benzphetamine.
Hydrocodone The metabolism of Voxelotor can be decreased when combined with Hydrocodone.
Methoxyflurane The metabolism of Voxelotor can be decreased when combined with Methoxyflurane.
Selegiline The metabolism of Voxelotor can be decreased when combined with Selegiline.
Promethazine The metabolism of Voxelotor can be decreased when combined with Promethazine.
Perhexiline The metabolism of Voxelotor can be decreased when combined with Perhexiline.
Bupropion The metabolism of Voxelotor can be decreased when combined with Bupropion.
Halothane The metabolism of Voxelotor can be decreased when combined with Halothane.

Target Protein

Hemoglobin subunit alpha HBA1

Referensi & Sumber

Synthesis reference: Zhe Li, Nathan Guz, Yiyang Shao, Julieana Cocuz, Markus Frieser, George Petros Yiannikouros, Liang Liao.(2017).US10077249B2.Retrieved from: https://patents.google.com/patent/US10077249B2/en
Artikel (PubMed)
  • PMID: 31199090
    Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, Hassab H, Achebe MM, Alkindi S, Brown RC, Diuguid DL, Telfer P, Tsitsikas DA, Elghandour A, Gordeuk VR, Kanter J, Abboud MR, Lehrer-Graiwer J, Tonda M, Intondi A, Tong B, Howard J: A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease. N Engl J Med. 2019 Aug 8;381(6):509-519. doi: 10.1056/NEJMoa1903212. Epub 2019 Jun 14.
  • PMID: 30743314
    Hutchaleelaha A, Patel M, Washington C, Siu V, Allen E, Oksenberg D, Gretler DD, Mant T, Lehrer-Graiwer J: Pharmacokinetics and pharmacodynamics of voxelotor (GBT440) in healthy adults and patients with sickle cell disease. Br J Clin Pharmacol. 2019 Jun;85(6):1290-1302. doi: 10.1111/bcp.13896. Epub 2019 Mar 31.
  • PMID: 30655275
    Howard J, Hemmaway CJ, Telfer P, Layton DM, Porter J, Awogbade M, Mant T, Gretler DD, Dufu K, Hutchaleelaha A, Patel M, Siu V, Dixon S, Landsman N, Tonda M, Lehrer-Graiwer J: A phase 1/2 ascending dose study and open-label extension study of voxelotor in patients with sickle cell disease. Blood. 2019 Apr 25;133(17):1865-1875. doi: 10.1182/blood-2018-08-868893. Epub 2019 Jan 17.
  • PMID: 30499731
    Torres L, Conran N: Emerging pharmacotherapeutic approaches for the management of sickle cell disease. Expert Opin Pharmacother. 2019 Feb;20(2):173-186. doi: 10.1080/14656566.2018.1548610. Epub 2018 Nov 30.
  • PMID: 30873300
    Ataga KI, Desai PC: Advances in new drug therapies for the management of sickle cell disease. Expert Opin Orphan Drugs. 2018;6(5):329-343. doi: 10.1080/21678707.2018.1471983. Epub 2018 May 14.
  • PMID: 1641648
    Yarbro JW: Mechanism of action of hydroxyurea. Semin Oncol. 1992 Jun;19(3 Suppl 9):1-10.
  • PMID: 33489427
    Yenamandra A, Marjoncu D: Voxelotor: A Hemoglobin S Polymerization Inhibitor for the Treatment of Sickle Cell Disease. J Adv Pract Oncol. 2020 Nov-Dec;11(8):873-877. doi: 10.6004/jadpro.2020.11.8.7. Epub 2020 Nov 1.
Textbook
  • Ankit Mangla; Moavia Ehsan; Smita Maruvada (2019). Sickle Cell Anemia. Stat Pearls.

Contoh Produk & Brand

Produk: 4 • International brands: 0
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Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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