Peringatan Keamanan

The Lowest published toxic dose (TDLo) in mouse was 5 mg/kg/14D following intraperitoneal administration of an intermittent dose and 1.6 mg/kg/12D following subcutaneous administration of a continuous dose.L14198

The therapeutic dose of bortezomib is individualized in each patient to prevent overdose. Fatal outcomes occurred in humans following the administration of more than twice the recommended therapeutic dose of bortezomib. The symptoms from overdose included the acute onset of symptomatic hypotension and thrombocytopenia. As there is no known antidote for bortezomib overdosage, monitoring of vital signs and appropriate supportive care should be initiated when drug overdosage is suspected. In monkeys and dogs, increased heart rate, decreased contractility, hypotension, and death were observed with the intravenous dose as low as two times the recommended clinical dose on a mg/m2 basis. A case of a slight increase in the corrected QT interval leading to death occurred in dog studies.L14177

Bortezomib

DB00188

small molecule approved investigational

Deskripsi

Bortezomib is a dipeptide boronic acid derivative and proteasome inhibitor used to treat multiple myeloma and mantle cell lymphoma.A204083 The 26S proteasome is a protein complex that degrades ubiquitinated proteins in the ubiquitin-proteasome pathway: reversible inhibition of the 26S proteasome, leading to cell cycle arrest and apoptosis of cancer cells, is thought to be the main mechanism of action of bortezomib.L14180 However, multiple mechanisms may be involved in the anticancer activity of bortezomib.A204083

Bortezomib was first synthesized in 1995.A204083 In May 2003, bortezomib became the first anticancer proteasome inhibitor that was approved by the FDA under the trade name VELCADE.A204146 Phase I, II, III, and IV clinical trials are undergoing to investigate the therapeutic efficacy of bortezomib in leukemia, myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis, and solid tumours.A214307

Struktur Molekul 2D

Berat 384.237
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The mean elimination half-life of bortezomib ranged from 40 to 193 hours following a multiple dosing regimen at a 1 mg/m<sup>2</sup> dose. The half-life ranged from 76 to 108 hours after multiple dosing of 1.3 mg/m<sup>2</sup> bortezomib.[L14177]
Volume Distribusi The mean distribution volume of bortezomib ranged from approximately 498 to 1884 L/m<sup>2</sup> in patients with multiple myeloma receiving a single- or repeat-dose of 1 mg/m<sup>2</sup> or 1.3 mg/m<sup>2</sup>.[L14177] Bortezomib distributes into nearly all tissues, except for the adipose and brain tissue.[A204083]
Klirens (Clearance) Following the administration of a first dose of 1 mg/m<sup>2</sup> and 1.3 mg/m<sup>2</sup>, the mean mean total body clearances were 102 and 112 L/h, respectively. The clearances were 15 and 32 L/h after the subsequent dose of 1 and 1.3 mg/m<sup>2</sup>, respectively.[L14177]

Absorpsi

Following intravenous administration of 1 mg/m2 and 1.3 mg/m2 doses, the mean Cmax of bortezomib were 57 and 112 ng/mL, respectively. In a twice-weekly dosing regimen, the Cmax ranged from 67 to 106 ng/mL at the dose of 1 mg/m2 and 89 to 120 ng/mL for the 1.3 mg/m2 dose. In patients with multiple myeloma, the Cmax of bortezomib followig subcutaneous administration was lower than that of intravenously-administered dose; however, the total systemic exposure of the drug was equivalent for both routes of administration.L14177 There is a wide interpatient variability in drug plasma concentrations.L14180

Metabolisme

Bortezomib is primarily metabolized by CYP3A4, CYP2C19, and CYP1A2. CYP2D6 and CYP2C9 are also involved in drug metabolism, but to a smaller extent.L14177 Oxidative deboronation, which involves the removal of boronic acid from the parent compound, is the main metabolic pathway. Metabolites of bortezomib are pharmacologically inactive and more than 30 metabolites have been identified in human and animal studies.A204146

Rute Eliminasi

Bortezomib is eliminated by both renal and hepatic routes.A204146

Interaksi Makanan

4 Data
  • 1. Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of bortezomib.
  • 2. Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of bortezomib.
  • 3. Limit foods and supplements high in flavonoids. Flavonoids may interfere with the therapeutic action of this drug. Foods high in flavonoids include green vegetables, fruits, and green tea.
  • 4. Limit foods and supplements high in vitamin C. Vitamin C may interfere with the therapeutic action of this drug. Foods high in vitamin C include citrus fruits and beverages.

Interaksi Obat

1573 Data
Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Bortezomib.
Peginterferon alfa-2a The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Bortezomib.
Interferon alfa-n1 The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Bortezomib.
Interferon alfa-n3 The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Bortezomib.
Interferon gamma-1b The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Bortezomib.
Interferon alfa-2a The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Bortezomib.
Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Bortezomib.
Pegaspargase The risk or severity of adverse effects can be increased when Pegaspargase is combined with Bortezomib.
Interferon beta-1b The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Bortezomib.
Interferon alfacon-1 The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Bortezomib.
Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Bortezomib.
Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Bortezomib.
Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Bortezomib.
Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Bortezomib.
Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Bortezomib.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Bortezomib.
Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Bortezomib.
Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Bortezomib.
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Bortezomib.
Interferon alfa-2b The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Bortezomib.
Daclizumab The risk or severity of adverse effects can be increased when Daclizumab is combined with Bortezomib.
Phenylalanine The risk or severity of adverse effects can be increased when Phenylalanine is combined with Bortezomib.
Cladribine Bortezomib may increase the immunosuppressive activities of Cladribine.
Carmustine The risk or severity of adverse effects can be increased when Bortezomib is combined with Carmustine.
Amsacrine The risk or severity of adverse effects can be increased when Bortezomib is combined with Amsacrine.
Bleomycin The risk or severity of adverse effects can be increased when Bortezomib is combined with Bleomycin.
Chlorambucil The risk or severity of adverse effects can be increased when Bortezomib is combined with Chlorambucil.
Raltitrexed The risk or severity of adverse effects can be increased when Bortezomib is combined with Raltitrexed.
Mitomycin The risk or severity of adverse effects can be increased when Bortezomib is combined with Mitomycin.
Vindesine The risk or severity of adverse effects can be increased when Bortezomib is combined with Vindesine.
Floxuridine The risk or severity of adverse effects can be increased when Bortezomib is combined with Floxuridine.
Indomethacin The risk or severity of adverse effects can be increased when Bortezomib is combined with Indomethacin.
Tioguanine The risk or severity of adverse effects can be increased when Bortezomib is combined with Tioguanine.
Vinorelbine The risk or severity of adverse effects can be increased when Bortezomib is combined with Vinorelbine.
Dexrazoxane The risk or severity of adverse effects can be increased when Bortezomib is combined with Dexrazoxane.
Streptozocin The risk or severity of adverse effects can be increased when Bortezomib is combined with Streptozocin.
Trifluridine The risk or severity of adverse effects can be increased when Bortezomib is combined with Trifluridine.
Gemcitabine The risk or severity of adverse effects can be increased when Bortezomib is combined with Gemcitabine.
Lenalidomide The risk or severity of adverse effects can be increased when Bortezomib is combined with Lenalidomide.
Altretamine The risk or severity of adverse effects can be increased when Bortezomib is combined with Altretamine.
Zidovudine The risk or severity of adverse effects can be increased when Bortezomib is combined with Zidovudine.
Cisplatin The risk or severity of adverse effects can be increased when Bortezomib is combined with Cisplatin.
Oxaliplatin The risk or severity of QTc prolongation can be increased when Oxaliplatin is combined with Bortezomib.
Vincristine The risk or severity of adverse effects can be increased when Bortezomib is combined with Vincristine.
Fluorouracil The risk or severity of adverse effects can be increased when Bortezomib is combined with Fluorouracil.
Propylthiouracil The risk or severity of adverse effects can be increased when Bortezomib is combined with Propylthiouracil.
Pentostatin The risk or severity of adverse effects can be increased when Bortezomib is combined with Pentostatin.
Methotrexate The risk or severity of adverse effects can be increased when Bortezomib is combined with Methotrexate.
Linezolid The risk or severity of adverse effects can be increased when Bortezomib is combined with Linezolid.
Clofarabine The risk or severity of adverse effects can be increased when Bortezomib is combined with Clofarabine.
Prednisone The risk or severity of adverse effects can be increased when Bortezomib is combined with Prednisone.
Pemetrexed The risk or severity of adverse effects can be increased when Bortezomib is combined with Pemetrexed.
Fludrocortisone The risk or severity of adverse effects can be increased when Bortezomib is combined with Fludrocortisone.
Mycophenolate mofetil The risk or severity of adverse effects can be increased when Bortezomib is combined with Mycophenolate mofetil.
Tretinoin The risk or severity of cardiotoxicity can be increased when Bortezomib is combined with Tretinoin.
Irinotecan The risk or severity of adverse effects can be increased when Bortezomib is combined with Irinotecan.
Sulfasalazine The risk or severity of adverse effects can be increased when Bortezomib is combined with Sulfasalazine.
Dacarbazine The risk or severity of adverse effects can be increased when Bortezomib is combined with Dacarbazine.
Temozolomide The risk or severity of adverse effects can be increased when Bortezomib is combined with Temozolomide.
Penicillamine The risk or severity of adverse effects can be increased when Bortezomib is combined with Penicillamine.
Mechlorethamine The risk or severity of adverse effects can be increased when Bortezomib is combined with Mechlorethamine.
Azacitidine The risk or severity of adverse effects can be increased when Bortezomib is combined with Azacitidine.
Carboplatin The risk or severity of adverse effects can be increased when Bortezomib is combined with Carboplatin.
Dactinomycin The risk or severity of adverse effects can be increased when Bortezomib is combined with Dactinomycin.
Cytarabine The risk or severity of adverse effects can be increased when Bortezomib is combined with Cytarabine.
Azathioprine The risk or severity of adverse effects can be increased when Bortezomib is combined with Azathioprine.
Hydroxyurea The risk or severity of adverse effects can be increased when Bortezomib is combined with Hydroxyurea.
Mycophenolic acid The risk or severity of adverse effects can be increased when Bortezomib is combined with Mycophenolic acid.
Mercaptopurine The risk or severity of adverse effects can be increased when Bortezomib is combined with Mercaptopurine.
Thalidomide The risk or severity of peripheral neuropathy can be increased when Thalidomide is combined with Bortezomib.
Melphalan The risk or severity of adverse effects can be increased when Bortezomib is combined with Melphalan.
Fludarabine The risk or severity of adverse effects can be increased when Bortezomib is combined with Fludarabine.
Flucytosine The risk or severity of adverse effects can be increased when Bortezomib is combined with Flucytosine.
Trilostane The risk or severity of adverse effects can be increased when Bortezomib is combined with Trilostane.
Procarbazine The risk or severity of adverse effects can be increased when Bortezomib is combined with Procarbazine.
Idarubicin The risk or severity of adverse effects can be increased when Bortezomib is combined with Idarubicin.
Estramustine The risk or severity of adverse effects can be increased when Bortezomib is combined with Estramustine.
Lomustine The risk or severity of adverse effects can be increased when Bortezomib is combined with Lomustine.
Eculizumab The risk or severity of adverse effects can be increased when Bortezomib is combined with Eculizumab.
Decitabine The risk or severity of adverse effects can be increased when Bortezomib is combined with Decitabine.
Nelarabine The risk or severity of adverse effects can be increased when Bortezomib is combined with Nelarabine.
Ciclesonide The risk or severity of adverse effects can be increased when Bortezomib is combined with Ciclesonide.
Stepronin The risk or severity of adverse effects can be increased when Bortezomib is combined with Stepronin.
Hydroxychloroquine The risk or severity of adverse effects can be increased when Bortezomib is combined with Hydroxychloroquine.
Castanospermine The risk or severity of adverse effects can be increased when Bortezomib is combined with Castanospermine.
Vorinostat The therapeutic efficacy of Bortezomib can be increased when used in combination with Vorinostat.
2-Methoxyethanol The risk or severity of adverse effects can be increased when Bortezomib is combined with 2-Methoxyethanol.
Brequinar The risk or severity of adverse effects can be increased when Bortezomib is combined with Brequinar.
Thiotepa The risk or severity of adverse effects can be increased when Bortezomib is combined with Thiotepa.
Aldosterone The risk or severity of adverse effects can be increased when Bortezomib is combined with Aldosterone.
Interferon alfa The risk or severity of adverse effects can be increased when Bortezomib is combined with Interferon alfa.
Glatiramer The risk or severity of adverse effects can be increased when Bortezomib is combined with Glatiramer.
Briakinumab The risk or severity of adverse effects can be increased when Bortezomib is combined with Briakinumab.
Human interferon omega-1 The risk or severity of adverse effects can be increased when Bortezomib is combined with Human interferon omega-1.
Mepolizumab The risk or severity of adverse effects can be increased when Bortezomib is combined with Mepolizumab.
Abetimus The risk or severity of adverse effects can be increased when Bortezomib is combined with Abetimus.
Belatacept The risk or severity of adverse effects can be increased when Bortezomib is combined with Belatacept.
Bendamustine The risk or severity of adverse effects can be increased when Bortezomib is combined with Bendamustine.
Cabazitaxel The risk or severity of adverse effects can be increased when Bortezomib is combined with Cabazitaxel.
Pralatrexate The risk or severity of adverse effects can be increased when Bortezomib is combined with Pralatrexate.

Target Protein

Proteasome subunit beta type-5 PSMB5
Serine protease 1 PRSS1
Proteasome subunit beta type-1 PSMB1

Referensi & Sumber

Synthesis reference: Raghavendracharyulu Venkata Palle, Rajasekhar Kadaboina, Veerendeer Murki, Amarendhar Manda, Nageshwar Gunda, Ramaseshagiri Rao Pulla, Mallesha Hanmanthu, Narasimha Naidu Mopidevi, Suresh Kumar Ramdoss, "BORTEZOMIB AND PROCESS FOR PRODUCING SAME." U.S. Patent US20100226597, issued September 09, 2010.
Artikel (PubMed)
  • PMID: 14695130
    Voorhees PM, Dees EC, O'Neil B, Orlowski RZ: The proteasome as a target for cancer therapy. Clin Cancer Res. 2003 Dec 15;9(17):6316-25.
  • PMID: 10363983
    Adams J, Palombella VJ, Sausville EA, Johnson J, Destree A, Lazarus DD, Maas J, Pien CS, Prakash S, Elliott PJ: Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res. 1999 Jun 1;59(11):2615-22.
  • PMID: 15846363
    Berkers CR, Verdoes M, Lichtman E, Fiebiger E, Kessler BM, Anderson KC, Ploegh HL, Ovaa H, Galardy PJ: Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib. Nat Methods. 2005 May;2(5):357-62. Epub 2005 Apr 21.
  • PMID: 21247388
    Chen D, Frezza M, Schmitt S, Kanwar J, Dou QP: Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr Cancer Drug Targets. 2011 Mar;11(3):239-53. doi: 10.2174/156800911794519752.
  • PMID: 15688598
    Schwartz R, Davidson T: Pharmacology, pharmacokinetics, and practical applications of bortezomib. Oncology (Williston Park). 2004 Dec;18(14 Suppl 11):14-21.
  • PMID: 31731563
    Guedes RA, Aniceto N, Andrade MAP, Salvador JAR, Guedes RC: Chemical Patterns of Proteasome Inhibitors: Lessons Learned from Two Decades of Drug Design. Int J Mol Sci. 2019 Oct 25;20(21). pii: ijms20215326. doi: 10.3390/ijms20215326.

Contoh Produk & Brand

Produk: 55 • International brands: 0
Produk
  • Bortezomib
    Injection, powder, lyophilized, for solution • 3.5 mg/1 • Intravenous • US • Approved
  • Bortezomib
    Injection, powder, lyophilized, for solution • 1 mg/1mL • Intravenous • US • Approved
  • Bortezomib
    Injection, powder, lyophilized, for solution • 3.5 mg/1 • Intravenous; Subcutaneous • US • Generic • Approved
  • Bortezomib
    Injection, powder, lyophilized, for solution • 3.5 mg/1 • Intravenous; Subcutaneous • US • Generic • Approved
  • Bortezomib
    Injection, powder, lyophilized, for solution • 3.5 mg/1 • Intravenous; Subcutaneous • US • Generic • Approved
  • Bortezomib
    Injection, powder, lyophilized, for solution • 1 mg/1mL • Intravenous; Subcutaneous • US • Generic • Approved
  • Bortezomib
    Injection, powder, lyophilized, for solution • 3.5 mg/1 • Intravenous; Subcutaneous • US • Generic • Approved
  • Bortezomib
    Injection, powder, lyophilized, for solution • 1 mg/1mL • Intravenous; Subcutaneous • US • Generic • Approved
Menampilkan 8 dari 55 produk.

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