Peringatan Keamanan

There is limited information regarding the acute toxicity and overdosage of tovorafenib.

Tovorafenib

DB15266

small molecule approved investigational

Deskripsi

Tovorafenib is a selective type II RAF kinase inhibitor with anti-tumour activity.A263597 It was granted accelerated approval by the FDA, making it the first FDA approval of a systemic therapy for the treatment of pediatric low-grade glioma, with BRAF rearrangements.L50587 BRAF oncogenic mutations in cancers drive dysregulated cell growth, proliferation, and differentiation.A263602 Tovorafenib inhibits BRAF and blocks dysregulated signalling pathways related to cancer cell growth and survival.L50587

Struktur Molekul 2D

Berat 506.29
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) Tovorafenib terminal half-life is approximately 56 hours (33%).[L50582]
Volume Distribusi Tovorafenib apparent volume of distribution is 60 L/m<sup>2</sup> (23%).[L50582] It crosses the blood-brain barrier.[A263597]
Klirens (Clearance) The apparent clearance is 0.7 L/h/m2 (31%).[L50582]

Absorpsi

Tovorafenib steady-state maximum concentration (Cmax) is 6.9 µg/mL (23%) and the area under the concentration-time curve (AUC) is 508 µg*h/mL (31%). The time to reach a steady state of tovorafenib is 12 days (33%). Tovorafenib exposure increases in a dose-proportional manner. Tovorafenib median (minimum, maximum) time to achieve peak plasma concentration (Tmax) is 3 hours (1.5, 4 hours), following a single dose with tablets or oral suspension.L50582 No clinically significant differences in tovorafenib Cmax and AUC were observed following administration of tablets with a high-fat meal (approximately 859 total calories, 54% fat) compared to fasted conditions, but the Tmax was delayed to 6.5 hours.L50582

Metabolisme

Tovorafenib is primarily metabolized by aldehyde oxidase and CYP2C8 in vitro. CYP3A, CYP2C9, and CYP2C19 metabolize tovorafenib to a minor extent.L50582

Rute Eliminasi

Following a single oral dose of radiolabeled tovorafenib, 65% of the total radiolabeled dose was recovered in the feces (8.6% unchanged) and 27% of the dose was recovered in the urine (0.2% unchanged).L50582

Interaksi Makanan

1 Data
  • 1. Take with or without food. Food may delay Tmax, but has negligible effects on drug exposure.

Interaksi Obat

401 Data
Ritonavir The metabolism of Tovorafenib can be decreased when combined with Ritonavir.
Erlotinib The metabolism of Tovorafenib can be decreased when combined with Erlotinib.
Fluticasone propionate The metabolism of Tovorafenib can be decreased when combined with Fluticasone propionate.
Clopidogrel The metabolism of Tovorafenib can be decreased when combined with Clopidogrel.
Candesartan cilexetil The metabolism of Tovorafenib can be decreased when combined with Candesartan cilexetil.
Salmeterol The metabolism of Tovorafenib can be decreased when combined with Salmeterol.
Felodipine The metabolism of Tovorafenib can be decreased when combined with Felodipine.
Gemfibrozil The metabolism of Tovorafenib can be decreased when combined with Gemfibrozil.
Dabrafenib The metabolism of Tovorafenib can be decreased when combined with Dabrafenib.
Fluticasone The metabolism of Tovorafenib can be decreased when combined with Fluticasone.
Mometasone furoate The metabolism of Tovorafenib can be decreased when combined with Mometasone furoate.
Troglitazone The metabolism of Tovorafenib can be decreased when combined with Troglitazone.
Bexarotene The metabolism of Tovorafenib can be decreased when combined with Bexarotene.
Diltiazem The metabolism of Tovorafenib can be decreased when combined with Diltiazem.
Trimethoprim The metabolism of Tovorafenib can be decreased when combined with Trimethoprim.
Levothyroxine The metabolism of Tovorafenib can be decreased when combined with Levothyroxine.
Loratadine The metabolism of Tovorafenib can be decreased when combined with Loratadine.
Quinine The metabolism of Tovorafenib can be decreased when combined with Quinine.
Medroxyprogesterone acetate The metabolism of Tovorafenib can be decreased when combined with Medroxyprogesterone acetate.
Nicardipine The metabolism of Tovorafenib can be decreased when combined with Nicardipine.
Efavirenz The metabolism of Tovorafenib can be decreased when combined with Efavirenz.
Tamoxifen The metabolism of Tovorafenib can be decreased when combined with Tamoxifen.
Ketoconazole The metabolism of Tovorafenib can be decreased when combined with Ketoconazole.
Irbesartan The metabolism of Tovorafenib can be decreased when combined with Irbesartan.
Oxybutynin The metabolism of Tovorafenib can be decreased when combined with Oxybutynin.
Fluvastatin The metabolism of Tovorafenib can be decreased when combined with Fluvastatin.
Pioglitazone The metabolism of Tovorafenib can be decreased when combined with Pioglitazone.
Saquinavir The metabolism of Tovorafenib can be decreased when combined with Saquinavir.
Genistein The metabolism of Tovorafenib can be decreased when combined with Genistein.
Topiroxostat The metabolism of Tovorafenib can be decreased when combined with Topiroxostat.
Crisaborole The metabolism of Tovorafenib can be decreased when combined with Crisaborole.
Abiraterone The metabolism of Tovorafenib can be decreased when combined with Abiraterone.
Eltrombopag The metabolism of Tovorafenib can be decreased when combined with Eltrombopag.
Teriflunomide The metabolism of Tovorafenib can be decreased when combined with Teriflunomide.
Enzalutamide The metabolism of Tovorafenib can be decreased when combined with Enzalutamide.
Pirtobrutinib The metabolism of Tovorafenib can be decreased when combined with Pirtobrutinib.
Phenytoin The metabolism of Tovorafenib can be increased when combined with Phenytoin.
Secobarbital The metabolism of Tovorafenib can be increased when combined with Secobarbital.
Rifampin The metabolism of Tovorafenib can be increased when combined with Rifampicin.
Cyclosporine The metabolism of Cyclosporine can be increased when combined with Tovorafenib.
Bortezomib The metabolism of Bortezomib can be increased when combined with Tovorafenib.
Dofetilide The metabolism of Dofetilide can be increased when combined with Tovorafenib.
Cabergoline The metabolism of Cabergoline can be increased when combined with Tovorafenib.
Theophylline The metabolism of Theophylline can be increased when combined with Tovorafenib.
Vindesine The metabolism of Vindesine can be increased when combined with Tovorafenib.
Dihydroergotamine The metabolism of Dihydroergotamine can be increased when combined with Tovorafenib.
Vinorelbine The metabolism of Vinorelbine can be increased when combined with Tovorafenib.
Sorafenib The metabolism of Sorafenib can be increased when combined with Tovorafenib.
Teniposide The metabolism of Teniposide can be increased when combined with Tovorafenib.
Cyclophosphamide The metabolism of Cyclophosphamide can be increased when combined with Tovorafenib.
Nortriptyline The metabolism of Nortriptyline can be increased when combined with Tovorafenib.
Vincristine The metabolism of Vincristine can be increased when combined with Tovorafenib.
Methotrexate The metabolism of Methotrexate can be increased when combined with Tovorafenib.
Carbamazepine The metabolism of Carbamazepine can be increased when combined with Tovorafenib.
Vinblastine The metabolism of Vinblastine can be increased when combined with Tovorafenib.
Clonidine The metabolism of Clonidine can be increased when combined with Tovorafenib.
Astemizole The metabolism of Astemizole can be increased when combined with Tovorafenib.
Warfarin The metabolism of Warfarin can be increased when combined with Tovorafenib.
Ergotamine The metabolism of Ergotamine can be increased when combined with Tovorafenib.
Irinotecan The metabolism of Irinotecan can be increased when combined with Tovorafenib.
Etoposide The metabolism of Etoposide can be increased when combined with Tovorafenib.
Tacrolimus The metabolism of Tacrolimus can be increased when combined with Tovorafenib.
Conivaptan The metabolism of Conivaptan can be increased when combined with Tovorafenib.
Sirolimus The metabolism of Sirolimus can be increased when combined with Tovorafenib.
Quinidine The metabolism of Quinidine can be increased when combined with Tovorafenib.
Phenprocoumon The metabolism of Phenprocoumon can be increased when combined with Tovorafenib.
Doxorubicin The serum concentration of Doxorubicin can be decreased when it is combined with Tovorafenib.
Busulfan The metabolism of Busulfan can be increased when combined with Tovorafenib.
Pimozide The metabolism of Pimozide can be increased when combined with Tovorafenib.
Amiodarone The metabolism of Amiodarone can be increased when combined with Tovorafenib.
Bicalutamide The metabolism of Bicalutamide can be increased when combined with Tovorafenib.
Ifosfamide The metabolism of Ifosfamide can be increased when combined with Tovorafenib.
Aminophylline The metabolism of Aminophylline can be increased when combined with Tovorafenib.
Levacetylmethadol The metabolism of Levacetylmethadol can be increased when combined with Tovorafenib.
Paclitaxel The metabolism of Paclitaxel can be increased when combined with Tovorafenib.
Clomipramine The metabolism of Clomipramine can be increased when combined with Tovorafenib.
Docetaxel The metabolism of Docetaxel can be increased when combined with Tovorafenib.
Dasatinib The metabolism of Dasatinib can be increased when combined with Tovorafenib.
Sunitinib The metabolism of Sunitinib can be increased when combined with Tovorafenib.
Fosphenytoin The metabolism of Fosphenytoin can be increased when combined with Tovorafenib.
Digitoxin The metabolism of Digitoxin can be increased when combined with Tovorafenib.
Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Tovorafenib.
Everolimus The metabolism of Everolimus can be increased when combined with Tovorafenib.
Thiotepa The metabolism of Thiotepa can be increased when combined with Tovorafenib.
Ixabepilone The metabolism of Ixabepilone can be increased when combined with Tovorafenib.
Dronedarone The metabolism of Dronedarone can be increased when combined with Tovorafenib.
Nilotinib The metabolism of Nilotinib can be increased when combined with Tovorafenib.
Trabectedin The metabolism of Trabectedin can be increased when combined with Tovorafenib.
Cobimetinib The metabolism of Cobimetinib can be increased when combined with Tovorafenib.
Vandetanib The metabolism of Vandetanib can be increased when combined with Tovorafenib.
Trastuzumab emtansine The metabolism of Trastuzumab emtansine can be increased when combined with Tovorafenib.
Romidepsin The metabolism of Romidepsin can be increased when combined with Tovorafenib.
Tolvaptan The metabolism of Tolvaptan can be increased when combined with Tovorafenib.
Temsirolimus The metabolism of Temsirolimus can be increased when combined with Tovorafenib.
Pazopanib The metabolism of Pazopanib can be increased when combined with Tovorafenib.
Midostaurin The metabolism of Midostaurin can be increased when combined with Tovorafenib.
Panobinostat The metabolism of Panobinostat can be increased when combined with Tovorafenib.
Bosutinib The metabolism of Bosutinib can be increased when combined with Tovorafenib.
Axitinib The metabolism of Axitinib can be increased when combined with Tovorafenib.
Cabazitaxel The metabolism of Cabazitaxel can be increased when combined with Tovorafenib.

Target Protein

RAF proto-oncogene serine/threonine-protein kinase RAF1
Serine/threonine-protein kinase A-Raf ARAF
Serine/threonine-protein kinase B-raf BRAF

Referensi & Sumber

Artikel (PubMed)
  • PMID: 37978284
    Kilburn LB, Khuong-Quang DA, Hansford JR, Landi D, van der Lugt J, Leary SES, Driever PH, Bailey S, Perreault S, McCowage G, Waanders AJ, Ziegler DS, Witt O, Baxter PA, Kang HJ, Hassall TE, Han JW, Hargrave D, Franson AT, Yalon Oren M, Toledano H, Larouche V, Kline C, Abdelbaki MS, Jabado N, Gottardo NG, Gerber NU, Whipple NS, Segal D, Chi SN, Oren L, Tan EEK, Mueller S, Cornelio I, McLeod L, Zhao X, Walter A, Da Costa D, Manley P, Blackman SC, Packer RJ, Nysom K: The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial. Nat Med. 2024 Jan;30(1):207-217. doi: 10.1038/s41591-023-02668-y. Epub 2023 Nov 17.
  • PMID: 36963492
    Tkacik E, Li K, Gonzalez-Del Pino G, Ha BH, Vinals J, Park E, Beyett TS, Eck MJ: Structure and RAF family kinase isoform selectivity of type II RAF inhibitors tovorafenib and naporafenib. J Biol Chem. 2023 May;299(5):104634. doi: 10.1016/j.jbc.2023.104634. Epub 2023 Mar 22.
  • PMID: 38291372
    van Tilburg CM, Kilburn LB, Perreault S, Schmidt R, Azizi AA, Cruz-Martinez O, Zapotocky M, Scheinemann K, Meeteren AYNS, Sehested A, Opocher E, Driever PH, Avula S, Ziegler DS, Capper D, Koch A, Sahm F, Qiu J, Tsao LP, Blackman SC, Manley P, Milde T, Witt R, Jones DTW, Hargrave D, Witt O: LOGGIC/FIREFLY-2: a phase 3, randomized trial of tovorafenib vs. chemotherapy in pediatric and young adult patients with newly diagnosed low-grade glioma harboring an activating RAF alteration. BMC Cancer. 2024 Jan 30;24(1):147. doi: 10.1186/s12885-024-11820-x.

Contoh Produk & Brand

Produk: 2 • International brands: 0
Produk
  • Ojemda
    Kit; Powder, for suspension • 25 mg/1mL • Oral • US • Approved
  • Ojemda
    Tablet, film coated • 100 mg/1 • Oral • US • Approved

Sekuens Gen/Protein (FASTA)

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