Peringatan Keamanan

No information on the LD50 of leniolisib is available. If overdosage occurs, monitor the patient for any signs or symptoms of adverse reactions. Treatment of overdose with leniolisib consists of general supportive measures, including monitoring of vital signs as well as observation of the clinical status of the patient.L45753

Leniolisib

DB16217

small molecule approved investigational

Deskripsi

Leniolisib is a potent and selective inhibitor of phosphoinositide 3-kinase ? (PI3K?). The FDA approved leniolisib on March 24, 2023, making it the first treatment for activated phosphoinositide 3-kinase delta syndrome (APDS).L45758 APDS is a primary immunodeficiency caused by mutations in genes encoding the PI3K?, thereby increasing the activity of PI3K?, causing immune dysfunction, and elevating susceptibility to infections.A258473,A258463 Leniolisib works to inhibit hyperactive PI3K?.L45753 Investigations for using leniolisib in primary Sjögren’s syndrome are ongoing.A258468

Struktur Molekul 2D

Berat 450.466
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The effective half-life is approximately seven hours. The apparent terminal elimination half-life is approximately 10 hours.[L45753]
Volume Distribusi The systemic decay in leniolisib plasma concentration over time is bi-exponential, indicating a distribution delay toward peripheral tissues. The volume of distribution of leniolisib is estimated to be 28.5 L in patients with APDS.[L45753]
Klirens (Clearance) In one study, healthy volunteers received leniolisib single ascending doses up to 400 mg and multiple ascending doses up to 140 mg twice daily for 14 days. Oral drug clearance from plasma (CL/F) was 4 L/h.[A258478]

Absorpsi

The systemic drug exposure (AUC and Cmax) of leniolisib increases dose proportionally. During twice daily dosing approximately 12 hours apart, leniolisib accumulates approximately 1.4-fold (range of 1.0 to 2.2) in achieving steady-state. Steady-state drug concentrations can be expected to be reached after approximately two to three days. The Tmax is about one hour. Food has negligible effects on the systemic exposure of leniolisib.L45753

Metabolisme

About 60% of leniolisib is metabolized by the liver. Leniolisib undergoes oxidative metabolism, which is primarily mediated by CYP3A4 (94.5%), as well as CYP3A5 (3.5%), CYP1A2 (0.7%) and CYP2D6 (0.7%) to a minor extent.A258478,L45753 Few metabolites of leniolisib have been characterized in one study; however, no metabolites were abundant in plasma relative to the parent drug. Other metabolic pathways include dealkylation, demethylation, and hydroxylation.A258483 Other suggested excretion routes include intestinal secretion by BCRP and CYP1A1-mediated extrahepatic metabolism.A258478,L45753

Rute Eliminasi

The mean recovery of total 14C-radioactivity following a single oral dose of 70 mg 14C-leniolisib was 92.5% following 168 hours post-dose. About 67% and 25.5% of the recovered dose were in feces and urine, respectively. Of the recovered dose in urine, 6.32% was in unchanged parent drug form and the predominant drug-related material.L45753

Interaksi Makanan

1 Data
  • 1. Take with or without food. Food has negligible effects on systemic exposure of leniolisib.

Interaksi Obat

333 Data
Zolmitriptan The metabolism of Zolmitriptan can be decreased when combined with Leniolisib.
Eluxadoline The excretion of Eluxadoline can be decreased when combined with Leniolisib.
Folic acid The excretion of Folic acid can be decreased when combined with Leniolisib.
Pravastatin The excretion of Pravastatin can be decreased when combined with Leniolisib.
Conjugated estrogens The excretion of Conjugated estrogens can be decreased when combined with Leniolisib.
Gefitinib The excretion of Gefitinib can be decreased when combined with Leniolisib.
Allopurinol The excretion of Allopurinol can be decreased when combined with Leniolisib.
Cerivastatin The excretion of Cerivastatin can be decreased when combined with Leniolisib.
Teniposide The excretion of Teniposide can be decreased when combined with Leniolisib.
Prazosin The excretion of Prazosin can be decreased when combined with Leniolisib.
Raloxifene The excretion of Raloxifene can be decreased when combined with Leniolisib.
Celecoxib The excretion of Celecoxib can be decreased when combined with Leniolisib.
Zidovudine The excretion of Zidovudine can be decreased when combined with Leniolisib.
Ritonavir The excretion of Ritonavir can be decreased when combined with Leniolisib.
Oxaliplatin The excretion of Oxaliplatin can be decreased when combined with Leniolisib.
Vincristine The excretion of Vincristine can be decreased when combined with Leniolisib.
Fluorouracil The metabolism of Fluorouracil can be decreased when combined with Leniolisib.
Methotrexate The excretion of Methotrexate can be decreased when combined with Leniolisib.
Ivermectin The excretion of Ivermectin can be decreased when combined with Leniolisib.
Imatinib The excretion of Imatinib can be decreased when combined with Leniolisib.
Testosterone The excretion of Testosterone can be decreased when combined with Leniolisib.
Clofarabine The excretion of Clofarabine can be decreased when combined with Leniolisib.
Sumatriptan The excretion of Sumatriptan can be decreased when combined with Leniolisib.
Tamoxifen The metabolism of Tamoxifen can be decreased when combined with Leniolisib.
Mycophenolate mofetil The excretion of Mycophenolate mofetil can be decreased when combined with Leniolisib.
Daunorubicin The excretion of Daunorubicin can be decreased when combined with Leniolisib.
Nitrofurantoin The excretion of Nitrofurantoin can be decreased when combined with Leniolisib.
Lamivudine The excretion of Lamivudine can be decreased when combined with Leniolisib.
Riluzole The excretion of Riluzole can be decreased when combined with Leniolisib.
Irinotecan The excretion of Irinotecan can be decreased when combined with Leniolisib.
Etoposide The metabolism of Etoposide can be decreased when combined with Leniolisib.
Sulfasalazine The excretion of Sulfasalazine can be decreased when combined with Leniolisib.
Donepezil The excretion of Donepezil can be decreased when combined with Leniolisib.
Dactinomycin The excretion of Dactinomycin can be decreased when combined with Leniolisib.
Ezetimibe The excretion of Ezetimibe can be decreased when combined with Leniolisib.
Doxorubicin The excretion of Doxorubicin can be decreased when combined with Leniolisib.
Glyburide The excretion of Glyburide can be decreased when combined with Leniolisib.
Topotecan The excretion of Topotecan can be decreased when combined with Leniolisib.
Tegaserod The excretion of Tegaserod can be decreased when combined with Leniolisib.
Leflunomide The excretion of Leflunomide can be decreased when combined with Leniolisib.
Rosuvastatin The excretion of Rosuvastatin can be decreased when combined with Leniolisib.
Mitoxantrone The excretion of Mitoxantrone can be decreased when combined with Leniolisib.
Dasatinib The metabolism of Dasatinib can be decreased when combined with Leniolisib.
Alvocidib The excretion of Alvocidib can be decreased when combined with Leniolisib.
Camptothecin The excretion of Camptothecin can be decreased when combined with Leniolisib.
Nilotinib The excretion of Nilotinib can be decreased when combined with Leniolisib.
Rivaroxaban The excretion of Rivaroxaban can be decreased when combined with Leniolisib.
Simeprevir The excretion of Simeprevir can be decreased when combined with Leniolisib.
Pazopanib The excretion of Pazopanib can be decreased when combined with Leniolisib.
Apixaban The excretion of Apixaban can be decreased when combined with Leniolisib.
Pralatrexate The excretion of Pralatrexate can be decreased when combined with Leniolisib.
Teriflunomide The excretion of Teriflunomide can be decreased when combined with Leniolisib.
Vemurafenib The excretion of Vemurafenib can be decreased when combined with Leniolisib.
Ponatinib The excretion of Ponatinib can be decreased when combined with Leniolisib.
Dabrafenib The excretion of Dabrafenib can be decreased when combined with Leniolisib.
Afatinib The excretion of Afatinib can be decreased when combined with Leniolisib.
Dolutegravir The excretion of Dolutegravir can be decreased when combined with Leniolisib.
Riociguat The excretion of Riociguat can be decreased when combined with Leniolisib.
Sofosbuvir The excretion of Sofosbuvir can be decreased when combined with Leniolisib.
Idelalisib The excretion of Idelalisib can be decreased when combined with Leniolisib.
Palbociclib The excretion of Palbociclib can be decreased when combined with Leniolisib.
Lenvatinib The excretion of Lenvatinib can be decreased when combined with Leniolisib.
Fimasartan The excretion of Fimasartan can be decreased when combined with Leniolisib.
Ombitasvir The excretion of Ombitasvir can be decreased when combined with Leniolisib.
Tenofovir alafenamide The excretion of Tenofovir alafenamide can be decreased when combined with Leniolisib.
Osimertinib The excretion of Osimertinib can be decreased when combined with Leniolisib.
Venetoclax The excretion of Venetoclax can be decreased when combined with Leniolisib.
Velpatasvir The excretion of Velpatasvir can be decreased when combined with Leniolisib.
Tucatinib The excretion of Tucatinib can be decreased when combined with Leniolisib.
Selumetinib The excretion of Selumetinib can be decreased when combined with Leniolisib.
Talazoparib The excretion of Talazoparib can be decreased when combined with Leniolisib.
Fostemsavir The excretion of Fostemsavir can be decreased when combined with Leniolisib.
Revefenacin Leniolisib may decrease the excretion rate of Revefenacin which could result in a higher serum level.
Delafloxacin The excretion of Delafloxacin can be decreased when combined with Leniolisib.
Duvelisib The excretion of Duvelisib can be decreased when combined with Leniolisib.
Dacomitinib The excretion of Dacomitinib can be decreased when combined with Leniolisib.
Glasdegib The excretion of Glasdegib can be decreased when combined with Leniolisib.
Abemaciclib The excretion of Abemaciclib can be decreased when combined with Leniolisib.
Alpelisib The excretion of Alpelisib can be decreased when combined with Leniolisib.
Voxilaprevir The excretion of Voxilaprevir can be decreased when combined with Leniolisib.
Brigatinib The excretion of Brigatinib can be decreased when combined with Leniolisib.
Rucaparib The excretion of Rucaparib can be decreased when combined with Leniolisib.
Rimegepant The serum concentration of Rimegepant can be increased when it is combined with Leniolisib.
Copanlisib The excretion of Copanlisib can be decreased when combined with Leniolisib.
Ozanimod Leniolisib may decrease the excretion rate of Ozanimod which could result in a higher serum level.
Tazemetostat The excretion of Tazemetostat can be decreased when combined with Leniolisib.
Darolutamide The excretion of Darolutamide can be decreased when combined with Leniolisib.
Lusutrombopag The excretion of Lusutrombopag can be decreased when combined with Leniolisib.
Enasidenib The metabolism of Enasidenib can be decreased when combined with Leniolisib.
Pibrentasvir The excretion of Pibrentasvir can be decreased when combined with Leniolisib.
Glecaprevir The excretion of Glecaprevir can be decreased when combined with Leniolisib.
Testosterone cypionate The excretion of Testosterone cypionate can be decreased when combined with Leniolisib.
Testosterone enanthate The excretion of Testosterone enanthate can be decreased when combined with Leniolisib.
Ripretinib The excretion of Ripretinib can be decreased when combined with Leniolisib.
Ubrogepant The excretion of Ubrogepant can be decreased when combined with Leniolisib.
Trilaciclib The excretion of Trilaciclib can be decreased when combined with Leniolisib.
Pralsetinib The excretion of Pralsetinib can be decreased when combined with Leniolisib.
Berotralstat The excretion of Berotralstat can be decreased when combined with Leniolisib.
Valsartan The excretion of Valsartan can be decreased when combined with Leniolisib.
Erythromycin The excretion of Erythromycin can be decreased when combined with Leniolisib.

Target Protein

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

Referensi & Sumber

Artikel (PubMed)
  • PMID: 29535736
    Michalovich D, Nejentsev S: Activated PI3 Kinase Delta Syndrome: From Genetics to Therapy. Front Immunol. 2018 Feb 27;9:369. doi: 10.3389/fimmu.2018.00369. eCollection 2018.
  • PMID: 28972011
    Rao VK, Webster S, Dalm VASH, Sediva A, van Hagen PM, Holland S, Rosenzweig SD, Christ AD, Sloth B, Cabanski M, Joshi AD, de Buck S, Doucet J, Guerini D, Kalis C, Pylvaenaeinen I, Soldermann N, Kashyap A, Uzel G, Lenardo MJ, Patel DD, Lucas CL, Burkhart C: Effective "activated PI3Kdelta syndrome"-targeted therapy with the PI3Kdelta inhibitor leniolisib. Blood. 2017 Nov 23;130(21):2307-2316. doi: 10.1182/blood-2017-08-801191. Epub 2017 Sep 29.
  • PMID: 28947947
    Hoegenauer K, Soldermann N, Zecri F, Strang RS, Graveleau N, Wolf RM, Cooke NG, Smith AB, Hollingworth GJ, Blanz J, Gutmann S, Rummel G, Littlewood-Evans A, Burkhart C: Discovery of CDZ173 (Leniolisib), Representing a Structurally Novel Class of PI3K Delta-Selective Inhibitors. ACS Med Chem Lett. 2017 Aug 25;8(9):975-980. doi: 10.1021/acsmedchemlett.7b00293. eCollection 2017 Sep 14.
  • PMID: 30171694
    De Buck S, Kucher K, Hara H, Gray C, Woessner R: CYP3A but not P-gp plays a relevant role in the in vivo intestinal and hepatic clearance of the delta-specific phosphoinositide-3 kinase inhibitor leniolisib. Biopharm Drug Dispos. 2018 Sep;39(8):394-402. doi: 10.1002/bdd.2157.
  • PMID: 30215545
    Pearson D, Garnier M, Luneau A, James AD, Walles M: (19)F-NMR-based determination of the absorption, metabolism and excretion of the oral phosphatidylinositol-3-kinase (PI3K) delta inhibitor leniolisib (CDZ173) in healthy volunteers. Xenobiotica. 2019 Aug;49(8):953-960. doi: 10.1080/00498254.2018.1523488. Epub 2018 Nov 29.
  • PMID: 15023437
    Fresno Vara JA, Casado E, de Castro J, Cejas P, Belda-Iniesta C, Gonzalez-Baron M: PI3K/Akt signalling pathway and cancer. Cancer Treat Rev. 2004 Apr;30(2):193-204. doi: 10.1016/j.ctrv.2003.07.007.
  • PMID: 15505410
    Osaki M, Oshimura M, Ito H: PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis. 2004 Nov;9(6):667-76. doi: 10.1023/B:APPT.0000045801.15585.dd.
  • PMID: 24897931
    Martini M, De Santis MC, Braccini L, Gulluni F, Hirsch E: PI3K/AKT signaling pathway and cancer: an updated review. Ann Med. 2014 Sep;46(6):372-83. doi: 10.3109/07853890.2014.912836. Epub 2014 Jun 5.

Contoh Produk & Brand

Produk: 1 • International brands: 0
Produk
  • Joenja
    Tablet, film coated • 70 mg/1 • Oral • US • Approved

Sekuens Gen/Protein (FASTA)

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