Peringatan Keamanan

Treatment with brigatinib generated not mutagenic chromosomal damage. Testicular toxicity, reported as lower weight of seminal vesicles and prostate gland, testicular tubular degeneration and lower weight as well as reduced size of testes with evidence of hypoespermatogenesis.FDA label

Brigatinib

DB12267

small molecule approved investigational

Deskripsi

Brigatinib, originally named AP26113, is a reversible dual inhibitor of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR). It presents selectivity against the mutant forms of EGFR compared to the wild-type.A31311 It also exhibits selectivity against 9 different Crizotinib-resistant mutants of the EML4-ALK fusion gene, which is a pivotal player in the transformation of susceptible lung parenchyma.A31313 Brigatinib was developed by Ariad Pharmaceuticals, a subsidiary of Takeda Pharmaceutical Company Limited, and FDA-approved on April 28, 2017.L1026

Struktur Molekul 2D

Berat 584.1
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The half-life of brigatinib at steady-state was 25 hours.[L1028]
Volume Distribusi The apparent volume of distribution at steady state is 153 L.[A31320]
Klirens (Clearance) After oral administration of180 mg of brigatinib, the apparent oral clearance at steady-state is 12.7 L/h.[L1028]

Absorpsi

Administration of brigatinib at a concentration of 90 mg generates a Cmax of 552 ng/ml and AUC of 8165 ng h/ml while the administration of 180 mg presents a Cmax of 1452 ng/ml and AUC of 20276 ng h/ml. It has a dose proportional exposure with an accumulation ratio on the range of 1.9 to 2.4. Following oral administration of brigatinib, the Tmax is presented in a range from 1 to 4 hours. Consumption of a high-fat meal compared to overnight fasting reduces Cmax by 13% without presenting an effect on AUC.A31320

Metabolisme

Brigatinib is metabolized by CYP2C8 (72.4%) and CYP3A4 (27.6%) in human liver microsomes and hepatocytes. The two major metabolites generated are the N-demethylated form and the cysteine conjugated form. Oral administration of radiolabelled brigatinib showed the systemic presence of 91.5% in the unchanged form and 3.5% of the primary metabolite AP26123. The AUC of AP26123 is less than 10% of the AUC of brigatinib and presented an inhibitory effect 3 fold lower.L1028

Rute Eliminasi

The elimination of brigatinib is divided in 65% in feces and 25% in urine. From the elimination in both compartments, the unchanged for of brigatinib represented 41% of the total in feces and 86% in urine.L1028

Interaksi Makanan

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

Interaksi Obat

736 Data
Modafinil The metabolism of Brigatinib can be increased when combined with Modafinil.
Armodafinil The metabolism of Brigatinib can be increased when combined with Armodafinil.
Aripiprazole The metabolism of Aripiprazole can be increased when combined with Brigatinib.
Aripiprazole lauroxil The metabolism of Aripiprazole lauroxil can be increased when combined with Brigatinib.
Metreleptin The metabolism of Brigatinib can be increased when combined with Metreleptin.
Mifepristone The serum concentration of Brigatinib can be increased when it is combined with Mifepristone.
Ifosfamide The metabolism of Ifosfamide can be increased when combined with Brigatinib.
Perampanel The metabolism of Perampanel can be increased when combined with Brigatinib.
Warfarin The metabolism of Warfarin can be increased when combined with Brigatinib.
Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Brigatinib.
(R)-warfarin The metabolism of (R)-warfarin can be increased when combined with Brigatinib.
R,S-Warfarin alcohol The metabolism of R,S-Warfarin alcohol can be increased when combined with Brigatinib.
S,R-Warfarin alcohol The metabolism of S,R-Warfarin alcohol can be increased when combined with Brigatinib.
(S)-Warfarin The metabolism of (S)-Warfarin can be increased when combined with Brigatinib.
Crizotinib The metabolism of Brigatinib can be decreased when combined with Crizotinib.
Erlotinib The serum concentration of Erlotinib can be decreased when it is combined with Brigatinib.
Pitolisant The serum concentration of Brigatinib can be decreased when it is combined with Pitolisant.
Pravastatin Pravastatin may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Pantoprazole Pantoprazole may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Sulfasalazine Sulfasalazine may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Telmisartan Telmisartan may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Ezetimibe Brigatinib may decrease the excretion rate of Ezetimibe which could result in a higher serum level.
Novobiocin Novobiocin may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Hesperetin Hesperetin may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Daidzin Daidzin may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Naringenin Naringenin may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Taurocholic acid Taurocholic acid may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Elacridar Elacridar may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Safinamide Safinamide may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Afatinib Afatinib may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Cannabidiol The serum concentration of Brigatinib can be increased when it is combined with Cannabidiol.
Daclatasvir Daclatasvir may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Rolapitant Rolapitant may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Paritaprevir Paritaprevir may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Folic acid Brigatinib may decrease the excretion rate of Folic acid which could result in a higher serum level.
Conjugated estrogens Brigatinib may decrease the excretion rate of Conjugated estrogens which could result in a higher serum level.
Allopurinol Brigatinib may decrease the excretion rate of Allopurinol which could result in a higher serum level.
Prazosin Brigatinib may decrease the excretion rate of Prazosin which could result in a higher serum level.
Oxaliplatin Brigatinib may decrease the excretion rate of Oxaliplatin which could result in a higher serum level.
Clofarabine Brigatinib may decrease the excretion rate of Clofarabine which could result in a higher serum level.
Sumatriptan Brigatinib may decrease the excretion rate of Sumatriptan which could result in a higher serum level.
Nitrofurantoin Brigatinib may decrease the excretion rate of Nitrofurantoin which could result in a higher serum level.
Lamivudine Brigatinib may decrease the excretion rate of Lamivudine which could result in a higher serum level.
Riluzole Brigatinib may decrease the excretion rate of Riluzole which could result in a higher serum level.
Dactinomycin Brigatinib may decrease the excretion rate of Dactinomycin which could result in a higher serum level.
Leflunomide Brigatinib may decrease the excretion rate of Leflunomide which could result in a higher serum level.
Alvocidib Brigatinib may decrease the excretion rate of Alvocidib which could result in a higher serum level.
Camptothecin Brigatinib may decrease the excretion rate of Camptothecin which could result in a higher serum level.
Dolutegravir Brigatinib may decrease the excretion rate of Dolutegravir which could result in a higher serum level.
Sofosbuvir Brigatinib may decrease the excretion rate of Sofosbuvir which could result in a higher serum level.
Fimasartan Brigatinib may decrease the excretion rate of Fimasartan which could result in a higher serum level.
Talazoparib The serum concentration of Talazoparib can be increased when it is combined with Brigatinib.
Revefenacin Brigatinib may decrease the excretion rate of Revefenacin which could result in a higher serum level.
Delafloxacin Brigatinib may decrease the excretion rate of Delafloxacin which could result in a higher serum level.
Lusutrombopag Brigatinib may decrease the excretion rate of Lusutrombopag which could result in a higher serum level.
Pibrentasvir Brigatinib may decrease the excretion rate of Pibrentasvir which could result in a higher serum level.
Nabiximols Nabiximols may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Fedratinib The serum concentration of Brigatinib can be increased when it is combined with Fedratinib.
Caffeine Caffeine may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Donepezil Brigatinib may decrease the excretion rate of Donepezil which could result in a higher serum level.
Rivaroxaban Brigatinib may decrease the excretion rate of Rivaroxaban which could result in a higher serum level.
Pralatrexate Brigatinib may decrease the excretion rate of Pralatrexate which could result in a higher serum level.
Ripretinib Brigatinib may decrease the excretion rate of Ripretinib which could result in a higher serum level.
Fostemsavir Fostemsavir may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Vandetanib Vandetanib may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Vismodegib Vismodegib may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Alectinib Alectinib may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Vincristine Brigatinib may decrease the excretion rate of Vincristine which could result in a higher serum level.
Methotrexate Brigatinib may decrease the excretion rate of Methotrexate which could result in a higher serum level.
Irinotecan Brigatinib may decrease the excretion rate of Irinotecan which could result in a higher serum level.
Copanlisib Brigatinib may decrease the excretion rate of Copanlisib which could result in a higher serum level.
Progesterone Progesterone may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Sunitinib Sunitinib may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Ivermectin Brigatinib may decrease the excretion rate of Ivermectin which could result in a higher serum level.
Mitoxantrone Brigatinib may decrease the excretion rate of Mitoxantrone which could result in a higher serum level.
Lenvatinib Brigatinib may decrease the excretion rate of Lenvatinib which could result in a higher serum level.
Gefitinib Gefitinib may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Etoposide Brigatinib may decrease the excretion rate of Etoposide which could result in a higher serum level.
Trilaciclib Brigatinib may decrease the excretion rate of Trilaciclib which could result in a higher serum level.
Avanafil The serum concentration of Avanafil can be increased when it is combined with Brigatinib.
Tepotinib Tepotinib may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Rabeprazole Rabeprazole may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Regorafenib Regorafenib may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Belumosudil Belumosudil may decrease the excretion rate of Brigatinib which could result in a higher serum level.
Segesterone acetate The metabolism of Segesterone acetate can be increased when combined with Brigatinib.
Cholesterol Cholesterol may increase the excretion rate of Brigatinib which could result in a lower serum level and potentially a reduction in efficacy.
Venlafaxine Venlafaxine may increase the excretion rate of Brigatinib which could result in a lower serum level and potentially a reduction in efficacy.
Bexarotene The metabolism of Brigatinib can be increased when combined with Bexarotene.
Bosentan The metabolism of Brigatinib can be increased when combined with Bosentan.
Nafcillin The metabolism of Brigatinib can be increased when combined with Nafcillin.
Etravirine The metabolism of Brigatinib can be increased when combined with Etravirine.
Avasimibe The metabolism of Brigatinib can be increased when combined with Avasimibe.
Echinacea The metabolism of Brigatinib can be increased when combined with Echinacea.
Dexamethasone acetate The metabolism of Brigatinib can be increased when combined with Dexamethasone acetate.
Genistein The metabolism of Brigatinib can be increased when combined with Genistein.
Rufinamide The metabolism of Brigatinib can be increased when combined with Rufinamide.
Rifabutin The metabolism of Brigatinib can be increased when combined with Rifabutin.
Topiramate The metabolism of Brigatinib can be increased when combined with Topiramate.
Felbamate The metabolism of Brigatinib can be increased when combined with Felbamate.
Oritavancin The metabolism of Brigatinib can be increased when combined with Oritavancin.

Target Protein

ALK tyrosine kinase receptor ALK
Epidermal growth factor receptor EGFR
Tyrosine-protein kinase ABL1 ABL1
Insulin-like growth factor 1 receptor IGF1R
Receptor-type tyrosine-protein kinase FLT3 FLT3
Insulin receptor INSR
Hepatocyte growth factor receptor MET
Receptor tyrosine-protein kinase erbB-4 ERBB4
Receptor tyrosine-protein kinase erbB-2 ERBB2

Referensi & Sumber

Artikel (PubMed)
  • PMID: 23239810
    Ceccon M, Mologni L, Bisson W, Scapozza L, Gambacorti-Passerini C: Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors. Mol Cancer Res. 2013 Feb;11(2):122-32. doi: 10.1158/1541-7786.MCR-12-0569. Epub 2012 Dec 13.
  • PMID: 25888090
    Iragavarapu C, Mustafa M, Akinleye A, Furqan M, Mittal V, Cang S, Liu D: Novel ALK inhibitors in clinical use and development. J Hematol Oncol. 2015 Feb 27;8:17. doi: 10.1186/s13045-015-0122-8.
  • PMID: 28680831
    Rashdan S, Gerber DE: A crowded, but still varied, space: brigatinib in anaplastic lymphoma kinase-rearranged non-small cell lung cancer. Transl Cancer Res. 2017 Feb;6(Suppl 1):S78-S82. doi: 10.21037/tcr.2017.02.12.
  • PMID: 28872581
    Sabir SR, Yeoh S, Jackson G, Bayliss R: EML4-ALK Variants: Biological and Molecular Properties, and the Implications for Patients. Cancers (Basel). 2017 Sep 5;9(9). pii: E118. doi: 10.3390/cancers9090118.
  • PMID: 28435288
    Sabari JK, Santini FC, Schram AM, Bergagnini I, Chen R, Mrad C, Lai WV, Arbour KC, Drilon A: The activity, safety, and evolving role of brigatinib in patients with ALK-rearranged non-small cell lung cancers. Onco Targets Ther. 2017 Apr 6;10:1983-1992. doi: 10.2147/OTT.S109295. eCollection 2017.
  • PMID: 27049722
    Siaw JT, Wan H, Pfeifer K, Rivera VM, Guan J, Palmer RH, Hallberg B: Brigatinib, an anaplastic lymphoma kinase inhibitor, abrogates activity and growth in ALK-positive neuroblastoma cells, Drosophila and mice. Oncotarget. 2016 May 17;7(20):29011-22. doi: 10.18632/oncotarget.8508.
  • PMID: 27144831
    Huang WS, Liu S, Zou D, Thomas M, Wang Y, Zhou T, Romero J, Kohlmann A, Li F, Qi J, Cai L, Dwight TA, Xu Y, Xu R, Dodd R, Toms A, Parillon L, Lu X, Anjum R, Zhang S, Wang F, Keats J, Wardwell SD, Ning Y, Xu Q, Moran LE, Mohemmad QK, Jang HG, Clackson T, Narasimhan NI, Rivera VM, Zhu X, Dalgarno D, Shakespeare WC: Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase. J Med Chem. 2016 May 26;59(10):4948-64. doi: 10.1021/acs.jmedchem.6b00306. Epub 2016 May 12.
  • PMID: 28597393
    Markham A: Brigatinib: First Global Approval. Drugs. 2017 Jul;77(10):1131-1135. doi: 10.1007/s40265-017-0776-3.

Contoh Produk & Brand

Produk: 22 • International brands: 0
Produk
  • Alunbrig
    Tablet, coated • 30 mg/1 • Oral • US • Approved
  • Alunbrig
    Tablet • 30 mg • Oral • Canada • Approved
  • Alunbrig
    Tablet • 90 mg • Oral • Canada • Approved
  • Alunbrig
    Tablet • 180 mg • Oral • Canada • Approved
  • Alunbrig
    Kit; Tablet • - • Oral • Canada • Approved
  • Alunbrig
    Kit; Tablet • - • Oral • Canada • Approved
  • Alunbrig
    Tablet, film coated • 30 mg • Oral • EU • Approved
  • Alunbrig
    Tablet, film coated • 30 mg • Oral • EU • Approved
Menampilkan 8 dari 22 produk.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
© 2025 Digital Pharmacy Research - Universitas Esa Unggul