Peringatan Keamanan

There is limited data on zanubrutinib overdose.

Zanubrutinib

DB15035

small molecule approved investigational

Deskripsi

Zanubrutinib is a novel Bruton's tyrosine kinase (BTK) inhibitor used for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.L10163 Mantle cell lymphoma is an aggressive mature B-cell non-Hodgkin lymphoma associated with early relapse, poor clinical outcomes, and long-term survival.A187967 BTK is an enzyme that plays a role in oncogenic signalling pathways, promoting the survival and proliferation of malignant B cells.A187985 Compared to the first-generation BTK inhibitor ibrutinib, zanubrutinib displays higher potency and selectivity for BTK with fewer off-target effects.A187958 Due to this enhanced selectivity towards BTK, zanubrutinib belongs to the second-generation BTK inhibitor drug group that also includes acalabrutinib, which was approved by the FDA in 2017.

Zanubrutinib was granted accelerated approval by the FDA in November 2019 based on clinical trial results that demonstrated an 84% overall response rate from zanubrutinib therapy in patients with MCL,L10166 which measures the proportion of patients in a trial whose tumour is entirely or partially destroyed by a drug.L10169 It is currently marketed under the trade name BRUKINSA™ and is available as oral capsules. In August 2021, the FDA granted accelerated approval to zanubrutinib for the treatment of adults with Waldenström’s macroglobulinemia.L39030 This indication is valid in the US, Europe, and Canada.L39367 In September 2021, zanubrutinib was granted another accelerated approval for the treatment of relapsed or refractory marginal zone lymphoma who have received at least one anti-CD20-based regimen.L39025 In October 2022, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended zanubrutinib be granted marketing authorization for the treatment of chronic lymphocytic leukemia.L43737

Struktur Molekul 2D

Berat 471.561
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) Following administration of a single oral dose of 160 mg or 320 mg of zanubrutinib, the mean half-life is approximately 2 to 4 hours.[L10163]
Volume Distribusi The geometric mean (%CV) apparent steady-state Vd is 881 (95%) L. The blood-to­ plasma ratio is about 0.7 to 0.8.[L10163]
Klirens (Clearance) The mean (%CV) apparent oral clearance (CL/F) of zanubrutinib is 182 (37%) L/h.[L10163]

Absorpsi

Following oral administration of zanubrutinib 160 mg twice daily and 320 mg once daily, the mean (%CV) zanubrutinib steady-state concentrations were 2,295 (37%) ng·h/mL and 2,180 (41%) ng·h/mL, respectively. The mean Cmax (%CV) was 314 (46%) ng/mL following 160 mg twice daily and 543 (51%) ng/mL following 320 mg once daily.L10163 The Cmax and AUC of zanubrutinib increase in a dose-proportional manner and there is minimal systemic accumulation after repeated dosing. The median Tmax is 2 hours.L10163

Metabolisme

Zanubrutinib is predominantly metabolized by CYP3A4.L10163 Its metabolites have not been characterized.

Rute Eliminasi

Following oral administration of 320 mg radiolabelled zanubrutinib, approximately 87% of the dose was excreted in the feces and about 8% of the dose was recovered in the urine, where less than 1% of the recovered drug comprised of unchanged parent drug.L10163

Interaksi Makanan

4 Data
  • 1. Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of zanubrutinib. Dose adjustment may be necessary if coadministered.
  • 2. Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of zanubrutinib.
  • 3. Take with a full glass of water.
  • 4. Take with or without food. Food does not significantly affect drug concentrations.

Interaksi Obat

567 Data
Armodafinil The metabolism of Zanubrutinib can be increased when combined with Armodafinil.
Metreleptin The metabolism of Zanubrutinib can be increased when combined with Metreleptin.
Crizotinib The metabolism of Zanubrutinib can be decreased when combined with Crizotinib.
Pitolisant The serum concentration of Zanubrutinib can be decreased when it is combined with Pitolisant.
Topiramate The metabolism of Zanubrutinib can be increased when combined with Topiramate.
Rifabutin The metabolism of Zanubrutinib can be increased when combined with Rifabutin.
Warfarin The metabolism of Zanubrutinib can be increased when combined with Warfarin.
Felbamate The metabolism of Zanubrutinib can be increased when combined with Felbamate.
Genistein The metabolism of Zanubrutinib can be increased when combined with Genistein.
Oritavancin The metabolism of Zanubrutinib can be increased when combined with Oritavancin.
Rufinamide The metabolism of Zanubrutinib can be increased when combined with Rufinamide.
Glycerol phenylbutyrate The metabolism of Zanubrutinib can be increased when combined with Glycerol phenylbutyrate.
Eslicarbazepine acetate The metabolism of Zanubrutinib can be increased when combined with Eslicarbazepine acetate.
Lesinurad The metabolism of Zanubrutinib can be increased when combined with Lesinurad.
Asunaprevir The metabolism of Zanubrutinib can be increased when combined with Asunaprevir.
Sarilumab The metabolism of Zanubrutinib can be increased when combined with Sarilumab.
Esketamine The metabolism of Zanubrutinib can be increased when combined with Esketamine.
Alpelisib The metabolism of Zanubrutinib can be increased when combined with Alpelisib.
Calcitriol The metabolism of Zanubrutinib can be increased when combined with Calcitriol.
Vitamin E The metabolism of Zanubrutinib can be increased when combined with Vitamin E.
Flunisolide The metabolism of Zanubrutinib can be increased when combined with Flunisolide.
Troglitazone The metabolism of Zanubrutinib can be increased when combined with Troglitazone.
Butalbital The metabolism of Zanubrutinib can be increased when combined with Butalbital.
Flucloxacillin The metabolism of Zanubrutinib can be increased when combined with Flucloxacillin.
Acetaminophen The metabolism of Zanubrutinib can be increased when combined with Acetaminophen.
Clobazam The metabolism of Zanubrutinib can be increased when combined with Clobazam.
Aminoglutethimide The metabolism of Zanubrutinib can be increased when combined with Aminoglutethimide.
Beclomethasone dipropionate The metabolism of Zanubrutinib can be increased when combined with Beclomethasone dipropionate.
Griseofulvin The metabolism of Zanubrutinib can be increased when combined with Griseofulvin.
Secobarbital The metabolism of Zanubrutinib can be increased when combined with Secobarbital.
Cerivastatin The metabolism of Zanubrutinib can be increased when combined with Cerivastatin.
Betamethasone The metabolism of Zanubrutinib can be increased when combined with Betamethasone.
Quinine The metabolism of Zanubrutinib can be increased when combined with Quinine.
Chlorpromazine The metabolism of Zanubrutinib can be increased when combined with Chlorpromazine.
Dicloxacillin The metabolism of Zanubrutinib can be increased when combined with Dicloxacillin.
Cyclophosphamide The metabolism of Zanubrutinib can be increased when combined with Cyclophosphamide.
Rofecoxib The metabolism of Zanubrutinib can be increased when combined with Rofecoxib.
Vinblastine The metabolism of Zanubrutinib can be increased when combined with Vinblastine.
Fluocinolone acetonide The metabolism of Zanubrutinib can be increased when combined with Fluocinolone acetonide.
Medroxyprogesterone acetate The metabolism of Zanubrutinib can be increased when combined with Medroxyprogesterone acetate.
Triamcinolone The metabolism of Zanubrutinib can be increased when combined with Triamcinolone.
Testosterone The metabolism of Zanubrutinib can be increased when combined with Testosterone.
Clofibrate The metabolism of Zanubrutinib can be increased when combined with Clofibrate.
Tamoxifen The metabolism of Zanubrutinib can be increased when combined with Tamoxifen.
Hydrocortisone The metabolism of Zanubrutinib can be increased when combined with Hydrocortisone.
Hydrocortamate The metabolism of Zanubrutinib can be increased when combined with Hydrocortamate.
Oxcarbazepine The metabolism of Zanubrutinib can be increased when combined with Oxcarbazepine.
Phenylbutazone The metabolism of Zanubrutinib can be increased when combined with Phenylbutazone.
Mifepristone The metabolism of Zanubrutinib can be increased when combined with Mifepristone.
Methylphenobarbital The metabolism of Zanubrutinib can be increased when combined with Methylphenobarbital.
Terbinafine The metabolism of Zanubrutinib can be increased when combined with Terbinafine.
Prednisolone The metabolism of Zanubrutinib can be increased when combined with Prednisolone.
Ethanol The metabolism of Zanubrutinib can be increased when combined with Ethanol.
Norgestimate The metabolism of Zanubrutinib can be increased when combined with Norgestimate.
Methylprednisolone The metabolism of Zanubrutinib can be increased when combined with Methylprednisolone.
Metyrapone The metabolism of Zanubrutinib can be increased when combined with Metyrapone.
Probenecid The metabolism of Zanubrutinib can be increased when combined with Probenecid.
Sulfinpyrazone The metabolism of Zanubrutinib can be increased when combined with Sulfinpyrazone.
Thiamylal The metabolism of Zanubrutinib can be increased when combined with Thiamylal.
Ifosfamide The metabolism of Zanubrutinib can be increased when combined with Ifosfamide.
Rifapentine The metabolism of Zanubrutinib can be increased when combined with Rifapentine.
Budesonide The metabolism of Zanubrutinib can be increased when combined with Budesonide.
Paclitaxel The metabolism of Zanubrutinib can be increased when combined with Paclitaxel.
Corticotropin The metabolism of Zanubrutinib can be increased when combined with Corticotropin.
Cefradine The metabolism of Zanubrutinib can be increased when combined with Cefradine.
Amobarbital The metabolism of Zanubrutinib can be increased when combined with Amobarbital.
Aprobarbital The metabolism of Zanubrutinib can be increased when combined with Aprobarbital.
Cortisone acetate The metabolism of Zanubrutinib can be increased when combined with Cortisone acetate.
Paramethasone The metabolism of Zanubrutinib can be increased when combined with Paramethasone.
Barbital The metabolism of Zanubrutinib can be increased when combined with Barbital.
Deferasirox The metabolism of Zanubrutinib can be increased when combined with Deferasirox.
Tesmilifene The metabolism of Zanubrutinib can be increased when combined with Tesmilifene.
Clevidipine The metabolism of Zanubrutinib can be increased when combined with Clevidipine.
Fosaprepitant The metabolism of Zanubrutinib can be increased when combined with Fosaprepitant.
Seratrodast The metabolism of Zanubrutinib can be increased when combined with Seratrodast.
Vemurafenib The metabolism of Zanubrutinib can be increased when combined with Vemurafenib.
Perampanel The metabolism of Zanubrutinib can be increased when combined with Perampanel.
Formestane The metabolism of Zanubrutinib can be increased when combined with Formestane.
Fluprednidene The metabolism of Zanubrutinib can be increased when combined with Fluprednidene.
Barbexaclone The metabolism of Zanubrutinib can be increased when combined with Barbexaclone.
Meprednisone The metabolism of Zanubrutinib can be increased when combined with Meprednisone.
Dexamethasone isonicotinate The metabolism of Zanubrutinib can be increased when combined with Dexamethasone isonicotinate.
Deflazacort The metabolism of Zanubrutinib can be increased when combined with Deflazacort.
Cortivazol The metabolism of Zanubrutinib can be increased when combined with Cortivazol.
Prednylidene The metabolism of Zanubrutinib can be increased when combined with Prednylidene.
Cloprednol The metabolism of Zanubrutinib can be increased when combined with Cloprednol.
Fluticasone The metabolism of Zanubrutinib can be increased when combined with Fluticasone.
Enasidenib The metabolism of Zanubrutinib can be increased when combined with Enasidenib.
Estradiol acetate The metabolism of Zanubrutinib can be increased when combined with Estradiol acetate.
Estradiol benzoate The metabolism of Zanubrutinib can be increased when combined with Estradiol benzoate.
Estradiol cypionate The metabolism of Zanubrutinib can be increased when combined with Estradiol cypionate.
Estradiol dienanthate The metabolism of Zanubrutinib can be increased when combined with Estradiol dienanthate.
Estradiol valerate The metabolism of Zanubrutinib can be increased when combined with Estradiol valerate.
Mometasone furoate The metabolism of Zanubrutinib can be increased when combined with Mometasone furoate.
Hydrocortisone acetate The metabolism of Zanubrutinib can be increased when combined with Hydrocortisone acetate.
Hydrocortisone succinate The metabolism of Zanubrutinib can be increased when combined with Hydrocortisone succinate.
Ivosidenib The metabolism of Zanubrutinib can be increased when combined with Ivosidenib.
Eslicarbazepine The metabolism of Zanubrutinib can be increased when combined with Eslicarbazepine.
Prednisolone phosphate The metabolism of Zanubrutinib can be increased when combined with Prednisolone phosphate.
Prednisolone hemisuccinate The metabolism of Zanubrutinib can be increased when combined with Prednisolone hemisuccinate.

Target Protein

Tyrosine-protein kinase BTK BTK
Epidermal growth factor receptor EGFR
Receptor tyrosine-protein kinase erbB-2 ERBB2
Receptor tyrosine-protein kinase erbB-4 ERBB4
Tyrosine-protein kinase ITK/TSK ITK
Cytoplasmic tyrosine-protein kinase BMX BMX
Tyrosine-protein kinase JAK2 JAK2
Tyrosine-protein kinase Tec TEC
Tyrosine-protein kinase Blk BLK
Tyrosine-protein kinase JAK3 JAK3
Protein-tyrosine kinase 6 PTK6
Tyrosine-protein kinase Fgr FGR
Tyrosine-protein kinase FRK FRK
Tyrosine-protein kinase Lck LCK
Tyrosine-protein kinase TXK TXK

Referensi & Sumber

Synthesis reference: Guo Y, Liu Y, Hu N, et al. Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase. JOURNAL OF MEDICINAL CHEMISTRY. 62(17):7923-7940. doi:10.1021/acs.jmedchem.9b00687.
Artikel (PubMed)
  • PMID: 31420873
    Zou YX, Zhu HY, Li XT, Xia Y, Miao KR, Zhao SS, Wu YJ, Wang L, Xu W, Li JY: The impacts of zanubrutinib on immune cells in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. Hematol Oncol. 2019 Oct;37(4):392-400. doi: 10.1002/hon.2667. Epub 2019 Sep 13.
  • PMID: 31381333
    Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, Zhang B, Wei M, Liu J, Luo L, Tang Z, Song H, Guo Y, Liu X, Su D, Zhang S, Song X, Zhou X, Hong Y, Chen S, Cheng Z, Young S, Wei Q, Wang H, Wang Q, Lv L, Wang F, Xu H, Sun H, Xing H, Li N, Zhang W, Wang Z, Liu G, Sun Z, Zhou D, Li W, Liu L, Wang L, Wang Z: Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase. J Med Chem. 2019 Sep 12;62(17):7923-7940. doi: 10.1021/acs.jmedchem.9b00687. Epub 2019 Aug 19.
  • PMID: 30679329
    Tarantelli C, Zhang L, Curti E, Gaudio E, Spriano F, Priebe V, Cascione L, Arribas AJ, Zucca E, Rossi D, Stathis A, Bertoni F: The Bruton tyrosine kinase inhibitor zanubrutinib (BGB-3111) demonstrated synergies with other anti-lymphoma targeted agents. Haematologica. 2019 Jul;104(7):e307-e309. doi: 10.3324/haematol.2018.214759. Epub 2019 Jan 24.
  • PMID: 31340982
    Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW: Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. doi: 10.1182/blood.2019001160. Epub 2019 Jul 24.
  • PMID: 30109020
    Schieber M, Gordon LI, Karmali R: Current overview and treatment of mantle cell lymphoma. F1000Res. 2018 Jul 25;7. doi: 10.12688/f1000research.14122.1. eCollection 2018.
  • PMID: 29455639
    Pal Singh S, Dammeijer F, Hendriks RW: Role of Bruton's tyrosine kinase in B cells and malignancies. Mol Cancer. 2018 Feb 19;17(1):57. doi: 10.1186/s12943-018-0779-z.
Link

Contoh Produk & Brand

Produk: 3 • International brands: 0
Produk
  • Brukinsa
    Capsule • 80 mg • Oral • Canada • Approved
  • Brukinsa
    Capsule • 80 mg • Oral • EU • Approved
  • Brukinsa
    Capsule • 80 mg/1 • Oral • US • Approved

Sekuens Gen/Protein (FASTA)

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