Idelalisib

DB09054

small molecule approved

Deskripsi

Idelalisib is a phosphoinositide 3-kinase inhibitor indicated in the treatment of chronic lymphocytic leukemia (CLL), relapsed follicular B-cell non-Hodgkin lymphoma (FL), and relapsed small lymphocytic lymphoma (SLL). For the treatment of relapsed CLL, it is currently indicated as a second-line agent in combination with rituximab in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities, while in the treatment of FL and SLL it is intended to be used in patients who have received at least two prior systemic therapies. More specifically, idelalisib targets P110?, the delta isoform of the enzyme phosphatidylinositol-4,5-bisphosphate 3-kinase, also known as PI-3K. The PI-3Ks are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. In contrast to the other class IA PI3Ks p110? and p110?, p110? is principally expressed in leukocytes (white blood cells) and is important for the function of T cells, B cell, mast cells and neutrophils. By inhibiting this enzyme, idelalisib induces apoptosis of malignant cells and inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and C-X-C chemokine receptors type 5 and type 4 signalling, which are involved in trafficking and homing of B-cells to the lymph nodes and bone marrow. Treatment of lymphoma cells with idelalisib has been shown to result in inhibition of chemotaxis and adhesion, and reduced cell viability.

Struktur Molekul 2D

Berat 415.432
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The terminal elimination half-life is 8.2 hours.
Volume Distribusi 23 L
Klirens (Clearance) 14.9 L/hr

Absorpsi

Following oral administration, the median Tmax was observed at 1.5 hours.

Metabolisme

Idelalisib is metabolized by aldehyde oxidase and CYP3A to its major metabolite GS-563117, which is inactive against P110?. Idelalisib is also metabolized to a minor extent by UGT1A4.

Rute Eliminasi

Following a single dose of 150 mg of 14C idelalisib, 78% and 14% of the radioactivity was excreted in feces and urine, respectively. GS-563117, idelalisib's major metabolite, accounted for 49% of the radioactivity in the urine and 44% in the feces.

Interaksi Makanan

3 Data
  • 1. Avoid grapefruit products. Grapefruit inhibits the CYP3A metabolism of idelalisib, which may increase its serum concentration.
  • 2. Avoid St. John's Wort. This herb induces the CYP3A metabolism of idelalisib and may reduce its serum concentration.
  • 3. Take with or without food. Taking idelalisib with a high-fat meal may increase the AUC by 1.4 fold.

Interaksi Obat

978 Data
Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Idelalisib.
Peginterferon alfa-2a The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Idelalisib.
Interferon alfa-n1 The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Idelalisib.
Interferon alfa-n3 The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Idelalisib.
Peginterferon alfa-2b The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Idelalisib.
Interferon gamma-1b The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Idelalisib.
Interferon alfa-2a The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Idelalisib.
Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Idelalisib.
Pegaspargase The risk or severity of adverse effects can be increased when Pegaspargase is combined with Idelalisib.
Interferon beta-1b The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Idelalisib.
Interferon alfacon-1 The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Idelalisib.
Rituximab The risk or severity of adverse effects can be increased when Rituximab is combined with Idelalisib.
Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Idelalisib.
Muromonab The risk or severity of adverse effects can be increased when Muromonab is combined with Idelalisib.
Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Idelalisib.
Tositumomab The risk or severity of adverse effects can be increased when Tositumomab is combined with Idelalisib.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Idelalisib.
Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Idelalisib.
Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Idelalisib.
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Idelalisib.
Interferon alfa-2b The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Idelalisib.
Daclizumab The risk or severity of adverse effects can be increased when Daclizumab is combined with Idelalisib.
Phenylalanine The risk or severity of adverse effects can be increased when Phenylalanine is combined with Idelalisib.
Bortezomib The risk or severity of adverse effects can be increased when Bortezomib is combined with Idelalisib.
Cladribine Idelalisib may increase the immunosuppressive activities of Cladribine.
Carmustine The risk or severity of adverse effects can be increased when Carmustine is combined with Idelalisib.
Amsacrine The risk or severity of adverse effects can be increased when Amsacrine is combined with Idelalisib.
Bleomycin The risk or severity of adverse effects can be increased when Bleomycin is combined with Idelalisib.
Chlorambucil The risk or severity of adverse effects can be increased when Chlorambucil is combined with Idelalisib.
Raltitrexed The risk or severity of adverse effects can be increased when Raltitrexed is combined with Idelalisib.
Mitomycin The risk or severity of adverse effects can be increased when Mitomycin is combined with Idelalisib.
Vindesine The risk or severity of adverse effects can be increased when Vindesine is combined with Idelalisib.
Floxuridine The risk or severity of adverse effects can be increased when Floxuridine is combined with Idelalisib.
Indomethacin The risk or severity of adverse effects can be increased when Indomethacin is combined with Idelalisib.
Tioguanine The risk or severity of adverse effects can be increased when Tioguanine is combined with Idelalisib.
Dexrazoxane The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Idelalisib.
Streptozocin The risk or severity of adverse effects can be increased when Streptozocin is combined with Idelalisib.
Trifluridine The risk or severity of adverse effects can be increased when Trifluridine is combined with Idelalisib.
Gemcitabine The risk or severity of adverse effects can be increased when Gemcitabine is combined with Idelalisib.
Epirubicin The risk or severity of adverse effects can be increased when Epirubicin is combined with Idelalisib.
Lenalidomide The risk or severity of adverse effects can be increased when Lenalidomide is combined with Idelalisib.
Altretamine The risk or severity of adverse effects can be increased when Altretamine is combined with Idelalisib.
Zidovudine The risk or severity of adverse effects can be increased when Zidovudine is combined with Idelalisib.
Cisplatin The risk or severity of adverse effects can be increased when Cisplatin is combined with Idelalisib.
Oxaliplatin The risk or severity of adverse effects can be increased when Oxaliplatin is combined with Idelalisib.
Fluorouracil The risk or severity of adverse effects can be increased when Fluorouracil is combined with Idelalisib.
Propylthiouracil The risk or severity of adverse effects can be increased when Propylthiouracil is combined with Idelalisib.
Pentostatin The risk or severity of adverse effects can be increased when Pentostatin is combined with Idelalisib.
Linezolid The risk or severity of adverse effects can be increased when Linezolid is combined with Idelalisib.
Clofarabine The risk or severity of adverse effects can be increased when Clofarabine is combined with Idelalisib.
Pemetrexed The risk or severity of adverse effects can be increased when Pemetrexed is combined with Idelalisib.
Mycophenolate mofetil The risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Idelalisib.
Sulfasalazine The risk or severity of adverse effects can be increased when Sulfasalazine is combined with Idelalisib.
Dacarbazine The risk or severity of adverse effects can be increased when Dacarbazine is combined with Idelalisib.
Temozolomide The risk or severity of adverse effects can be increased when Temozolomide is combined with Idelalisib.
Penicillamine The risk or severity of adverse effects can be increased when Penicillamine is combined with Idelalisib.
Mechlorethamine The risk or severity of adverse effects can be increased when Mechlorethamine is combined with Idelalisib.
Azacitidine The risk or severity of adverse effects can be increased when Azacitidine is combined with Idelalisib.
Carboplatin The risk or severity of adverse effects can be increased when Carboplatin is combined with Idelalisib.
Dactinomycin The risk or severity of adverse effects can be increased when Dactinomycin is combined with Idelalisib.
Azathioprine The risk or severity of adverse effects can be increased when Azathioprine is combined with Idelalisib.
Hydroxyurea The risk or severity of adverse effects can be increased when Hydroxyurea is combined with Idelalisib.
Mycophenolic acid The risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Idelalisib.
Mercaptopurine The risk or severity of adverse effects can be increased when Mercaptopurine is combined with Idelalisib.
Thalidomide The metabolism of Idelalisib can be increased when combined with Thalidomide.
Melphalan The risk or severity of adverse effects can be increased when Melphalan is combined with Idelalisib.
Fludarabine The risk or severity of adverse effects can be increased when Fludarabine is combined with Idelalisib.
Flucytosine The risk or severity of adverse effects can be increased when Flucytosine is combined with Idelalisib.
Capecitabine The risk or severity of adverse effects can be increased when Capecitabine is combined with Idelalisib.
Procarbazine The risk or severity of adverse effects can be increased when Procarbazine is combined with Idelalisib.
Arsenic trioxide The risk or severity of adverse effects can be increased when Arsenic trioxide is combined with Idelalisib.
Idarubicin The risk or severity of adverse effects can be increased when Idarubicin is combined with Idelalisib.
Estramustine The risk or severity of adverse effects can be increased when Estramustine is combined with Idelalisib.
Lomustine The risk or severity of adverse effects can be increased when Lomustine is combined with Idelalisib.
Eculizumab The risk or severity of adverse effects can be increased when Eculizumab is combined with Idelalisib.
Decitabine The risk or severity of adverse effects can be increased when Decitabine is combined with Idelalisib.
Nelarabine The risk or severity of adverse effects can be increased when Nelarabine is combined with Idelalisib.
Ciclesonide The risk or severity of adverse effects can be increased when Ciclesonide is combined with Idelalisib.
Stepronin The risk or severity of adverse effects can be increased when Stepronin is combined with Idelalisib.
Hydroxychloroquine The risk or severity of adverse effects can be increased when Hydroxychloroquine is combined with Idelalisib.
Castanospermine The risk or severity of adverse effects can be increased when Castanospermine is combined with Idelalisib.
Vorinostat The risk or severity of adverse effects can be increased when Vorinostat is combined with Idelalisib.
2-Methoxyethanol The risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Idelalisib.
Brequinar The risk or severity of adverse effects can be increased when Brequinar is combined with Idelalisib.
Ixabepilone The risk or severity of adverse effects can be increased when Ixabepilone is combined with Idelalisib.
Pirfenidone The risk or severity of adverse effects can be increased when Pirfenidone is combined with Idelalisib.
Belinostat The risk or severity of adverse effects can be increased when Belinostat is combined with Idelalisib.
Interferon alfa The risk or severity of adverse effects can be increased when Interferon alfa is combined with Idelalisib.
Glatiramer The risk or severity of adverse effects can be increased when Glatiramer is combined with Idelalisib.
Briakinumab The risk or severity of adverse effects can be increased when Briakinumab is combined with Idelalisib.
Human interferon omega-1 The risk or severity of adverse effects can be increased when Human interferon omega-1 is combined with Idelalisib.
Mepolizumab The risk or severity of adverse effects can be increased when Mepolizumab is combined with Idelalisib.
Abetimus The risk or severity of adverse effects can be increased when Abetimus is combined with Idelalisib.
Belatacept The risk or severity of adverse effects can be increased when Belatacept is combined with Idelalisib.
Bendamustine The risk or severity of adverse effects can be increased when Bendamustine is combined with Idelalisib.
Pralatrexate The risk or severity of adverse effects can be increased when Pralatrexate is combined with Idelalisib.
Wortmannin The risk or severity of adverse effects can be increased when Wortmannin is combined with Idelalisib.
Eribulin The risk or severity of adverse effects can be increased when Eribulin is combined with Idelalisib.
Belimumab The risk or severity of adverse effects can be increased when Belimumab is combined with Idelalisib.
Teriflunomide The risk or severity of liver damage can be increased when Idelalisib is combined with Teriflunomide.

Target Protein

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform PIK3CD

Referensi & Sumber

Artikel (PubMed)
  • PMID: 25760671
    Jin F, Robeson M, Zhou H, Moyer C, Wilbert S, Murray B, Ramanathan S: Clinical drug interaction profile of idelalisib in healthy subjects. J Clin Pharmacol. 2015 Aug;55(8):909-19. doi: 10.1002/jcph.495. Epub 2015 May 6.
  • PMID: 24376763
    Fiorcari S, Brown WS, McIntyre BW, Estrov Z, Maffei R, O'Brien S, Sivina M, Hoellenriegel J, Wierda WG, Keating MJ, Ding W, Kay NE, Lannutti BJ, Marasca R, Burger JA: The PI3-kinase delta inhibitor idelalisib (GS-1101) targets integrin-mediated adhesion of chronic lymphocytic leukemia (CLL) cell to endothelial and marrow stromal cells. PLoS One. 2013 Dec 23;8(12):e83830. doi: 10.1371/journal.pone.0083830. eCollection 2013.
  • PMID: 24615776
    Flinn IW, Kahl BS, Leonard JP, Furman RR, Brown JR, Byrd JC, Wagner-Johnston ND, Coutre SE, Benson DM, Peterman S, Cho Y, Webb HK, Johnson DM, Yu AS, Ulrich RG, Godfrey WR, Miller LL, Spurgeon SE: Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-delta, as therapy for previously treated indolent non-Hodgkin lymphoma. Blood. 2014 May 29;123(22):3406-13. doi: 10.1182/blood-2013-11-538546. Epub 2014 Mar 10.
  • PMID: 24615777
    Brown JR, Byrd JC, Coutre SE, Benson DM, Flinn IW, Wagner-Johnston ND, Spurgeon SE, Kahl BS, Bello C, Webb HK, Johnson DM, Peterman S, Li D, Jahn TM, Lannutti BJ, Ulrich RG, Yu AS, Miller LL, Furman RR: Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110delta, for relapsed/refractory chronic lymphocytic leukemia. Blood. 2014 May 29;123(22):3390-7. doi: 10.1182/blood-2013-11-535047. Epub 2014 Mar 10.

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