Peringatan Keamanan

There is limited human data on the overdose of pexidartinib. In 4-week toxicology studies, the no-observed-adverse-effect levels (NOAELs) of pexidatrtinib were determined to be 10 mg/kg/day in rats and 6 mg/kg/day in dogs.L7895 Pexidartinib was shown to cause hepatotoxicity in clinical trials, including mixed or cholestatic hepatotoxicity,A182243 and embryo-fetal toxicity in animal studies.L7883

Pexidartinib

DB12978

small molecule approved investigational

Deskripsi

Pexidartinib is a selective tyrosine kinase inhibitor that works by inhibiting the colony-stimulating factor (CSF1)/CSF1 receptor pathway. Pexidartinib was originally developed by Daiichi Sankyo, Inc. and it was approved by the FDA in August 2019 as the first systemic therapy for adult patients with symptomatic tenosynovial giant cell tumor.L7901 Tenosynovial giant cell tumor is a rare form of non-malignant tumor that causes the synovium and tendon sheaths to thicken and overgrow, leading to damage in surrounding joint tissue.A182240,L7901 Debilitating symptoms often follow with tenosynovial giant cell tumors, along with a risk of significant functional limitations and a reduced quality of life in patients.L7901

While surgical resection is a current standard of care for tenosynovial giant cell tumor, there are tumor types where surgeries are deemed clinically ineffective with a high risk of lifetime recurrence.L7895 Pexidartinib works by blocking the immune responses that are activated in tenosynovial giant cell tumors. In clinical trials, pexidartinib was shown to promote improvements in patient symptoms and functional outcomes in TGCT.A182243 Pexidartinib is available in oral formulations and it is commonly marketed as Turalio.L7901

Struktur Molekul 2D

Berat 417.82
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The elimination half-life is about 26.6 hours.[L7883]
Volume Distribusi The apparent volume of distribution of pexidartinib is about 187 L.[L7883] In rats, pexidartinib was shown to penetrate into the central nervous system.[L7895]
Klirens (Clearance) The apparent clearance is about 5.1 L/h.[L7883]

Absorpsi

Following administration of single doses in healthy subjects and multiple doses in patients, the mean Cmax was 8625 ng/mL and the mean AUC was 77465 ngxh/mL. The median Tmax was 2.5 hours and the time to reach the steady state was approximately 7 days. Administration of pexidartinib with a high fat meal resulted in an increased drug Cmax and AUC by 100%, with a delay in Tmax by 2.5 hours.L7883

Metabolisme

Pexidartinib primarily undergoes oxidation mediated by hepatic CYP3A4 and glucuronidation by UGT1A4. Following UGT1A4-mediated glucuronidation, a major inactive N-glucuronide metabolite is formed with approximately 10% higher exposure than the parent drug after a single dose administration of pexidartinib.L7883 Based on the findings of in vitro studies, CYP1A2 and CYP2C9 may also play a minor role in drug metabolism.L7895

Rute Eliminasi

Pexidartinib is predominantly excreted via feces, where fecal excretion accounts for 65% of total pexidartinib elimination. Via this route of elimination, about 44% of the compound found in feces is recovered as unchanged parent drug. The renal elimination accounts for 27% of pexidartinib elimination, where more than 10% of the compound is found as the N-glucuronide metabolite.L7883

Interaksi Makanan

5 Data
  • 1. Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of pexidartinib.
  • 2. Avoid St. John's Wort. This herb induces the CYP3A metabolism of pexidartinib and may reduce its serum concentration.
  • 3. Do not take with or immediately after a high-fat meal. Taking pexidartinib with a high-fat meal may increase incidence and severity of adverse reactions, including hepatotoxicity.
  • 4. Take on an empty stomach. Take at least 1 hour before or 2 hours after eating a meal or snack.
  • 5. Take separate from antacids. Take antacids at least 2 hours before or after pexidartinib.

Interaksi Obat

646 Data
Modafinil The metabolism of Pexidartinib can be increased when combined with Modafinil.
Armodafinil The metabolism of Pexidartinib can be increased when combined with Armodafinil.
Irinotecan The risk or severity of neutropenia can be increased when Pexidartinib is combined with Irinotecan.
Metreleptin The metabolism of Pexidartinib can be increased when combined with Metreleptin.
Propacetamol The serum concentration of Propacetamol can be increased when it is combined with Pexidartinib.
Crizotinib The metabolism of Pexidartinib can be decreased when combined with Crizotinib.
Eluxadoline The serum concentration of Eluxadoline can be increased when it is combined with Pexidartinib.
Pravastatin The excretion of Pravastatin can be decreased when combined with Pexidartinib.
Valsartan The excretion of Valsartan can be decreased when combined with Pexidartinib.
Torasemide The excretion of Torasemide can be decreased when combined with Pexidartinib.
Conjugated estrogens The excretion of Conjugated estrogens can be decreased when combined with Pexidartinib.
Digoxin The excretion of Digoxin can be decreased when combined with Pexidartinib.
Caspofungin The excretion of Caspofungin can be decreased when combined with Pexidartinib.
Enalapril The excretion of Enalapril can be decreased when combined with Pexidartinib.
Sumatriptan The excretion of Sumatriptan can be decreased when combined with Pexidartinib.
Penicillamine The excretion of Penicillamine can be decreased when combined with Pexidartinib.
Repaglinide The excretion of Repaglinide can be decreased when combined with Pexidartinib.
Dinoprostone The excretion of Dinoprostone can be decreased when combined with Pexidartinib.
Fexofenadine The excretion of Fexofenadine can be decreased when combined with Pexidartinib.
Benzylpenicillin The excretion of Benzylpenicillin can be decreased when combined with Pexidartinib.
Ouabain The excretion of Ouabain can be decreased when combined with Pexidartinib.
Cholic Acid The excretion of Cholic Acid can be decreased when combined with Pexidartinib.
Taurocholic acid The excretion of Taurocholic acid can be decreased when combined with Pexidartinib.
Atrasentan The excretion of Atrasentan can be decreased when combined with Pexidartinib.
Ambrisentan The excretion of Ambrisentan can be decreased when combined with Pexidartinib.
Gimatecan The excretion of Gimatecan can be decreased when combined with Pexidartinib.
Temocapril The excretion of Temocapril can be decreased when combined with Pexidartinib.
Cholecystokinin The excretion of Cholecystokinin can be decreased when combined with Pexidartinib.
Gadoxetic acid The excretion of Gadoxetic acid can be decreased when combined with Pexidartinib.
Technetium Tc-99m mebrofenin The excretion of Technetium Tc-99m mebrofenin can be decreased when combined with Pexidartinib.
Fimasartan The excretion of Fimasartan can be decreased when combined with Pexidartinib.
Paritaprevir The excretion of Paritaprevir can be decreased when combined with Pexidartinib.
Selexipag The excretion of Selexipag can be decreased when combined with Pexidartinib.
Grazoprevir The excretion of Grazoprevir can be decreased when combined with Pexidartinib.
Voxilaprevir The excretion of Voxilaprevir can be decreased when combined with Pexidartinib.
Levosalbutamol The excretion of Levosalbutamol can be decreased when combined with Pexidartinib.
Belantamab mafodotin The excretion of Belantamab mafodotin can be decreased when combined with Pexidartinib.
Tramadol The metabolism of Tramadol can be decreased when combined with Pexidartinib.
Morphine The metabolism of Morphine can be decreased when combined with Pexidartinib.
Indomethacin The metabolism of Indomethacin can be decreased when combined with Pexidartinib.
Minoxidil The metabolism of Minoxidil can be decreased when combined with Pexidartinib.
Zidovudine The metabolism of Zidovudine can be decreased when combined with Pexidartinib.
Lamotrigine The metabolism of Lamotrigine can be decreased when combined with Pexidartinib.
Diclofenac The metabolism of Diclofenac can be decreased when combined with Pexidartinib.
Labetalol The metabolism of Labetalol can be decreased when combined with Pexidartinib.
Simvastatin The metabolism of Simvastatin can be decreased when combined with Pexidartinib.
Mycophenolate mofetil The metabolism of Mycophenolate mofetil can be decreased when combined with Pexidartinib.
Furosemide The metabolism of Furosemide can be decreased when combined with Pexidartinib.
Naltrexone Naltrexone may increase the hepatotoxic activities of Pexidartinib.
Flurbiprofen The metabolism of Flurbiprofen can be decreased when combined with Pexidartinib.
Estradiol The metabolism of Estradiol can be decreased when combined with Pexidartinib.
Naproxen The metabolism of Naproxen can be decreased when combined with Pexidartinib.
Tiagabine The metabolism of Tiagabine can be decreased when combined with Pexidartinib.
Zonisamide The metabolism of Zonisamide can be decreased when combined with Pexidartinib.
Fulvestrant The metabolism of Fulvestrant can be decreased when combined with Pexidartinib.
Ezetimibe The metabolism of Ezetimibe can be decreased when combined with Pexidartinib.
Ethinylestradiol The metabolism of Ethinylestradiol can be decreased when combined with Pexidartinib.
Ketoprofen The metabolism of Ketoprofen can be decreased when combined with Pexidartinib.
Abacavir The metabolism of Abacavir can be decreased when combined with Pexidartinib.
Ibuprofen The metabolism of Ibuprofen can be decreased when combined with Pexidartinib.
Glipizide The metabolism of Glipizide can be decreased when combined with Pexidartinib.
Atorvastatin The metabolism of Atorvastatin can be decreased when combined with Pexidartinib.
Carvedilol The metabolism of Carvedilol can be decreased when combined with Pexidartinib.
Gemfibrozil The metabolism of Gemfibrozil can be decreased when combined with Pexidartinib.
Alvocidib The metabolism of Alvocidib can be decreased when combined with Pexidartinib.
Ezogabine The metabolism of Ezogabine can be decreased when combined with Pexidartinib.
Indacaterol The metabolism of Indacaterol can be decreased when combined with Pexidartinib.
Bazedoxifene The metabolism of Bazedoxifene can be decreased when combined with Pexidartinib.
Muraglitazar The metabolism of Muraglitazar can be decreased when combined with Pexidartinib.
Gavestinel The metabolism of Gavestinel can be decreased when combined with Pexidartinib.
Raltegravir The metabolism of Raltegravir can be decreased when combined with Pexidartinib.
Dolutegravir The metabolism of Dolutegravir can be decreased when combined with Pexidartinib.
Bictegravir The metabolism of Bictegravir can be decreased when combined with Pexidartinib.
Delafloxacin The metabolism of Delafloxacin can be decreased when combined with Pexidartinib.
Elagolix The excretion of Elagolix can be decreased when combined with Pexidartinib.
Dexibuprofen The metabolism of Dexibuprofen can be decreased when combined with Pexidartinib.
Darolutamide The metabolism of Darolutamide can be decreased when combined with Pexidartinib.
Selumetinib The metabolism of Selumetinib can be decreased when combined with Pexidartinib.
Fluvastatin The metabolism of Fluvastatin can be decreased when combined with Pexidartinib.
Cabotegravir The metabolism of Cabotegravir can be decreased when combined with Pexidartinib.
Febuxostat The metabolism of Febuxostat can be decreased when combined with Pexidartinib.
Ponesimod The metabolism of Ponesimod can be decreased when combined with Pexidartinib.
Bexarotene The metabolism of Pexidartinib can be increased when combined with Bexarotene.
Nafcillin The metabolism of Pexidartinib can be increased when combined with Nafcillin.
Etravirine The metabolism of Pexidartinib can be increased when combined with Etravirine.
Avasimibe The metabolism of Pexidartinib can be increased when combined with Avasimibe.
Echinacea The metabolism of Pexidartinib can be increased when combined with Echinacea.
Dexamethasone acetate The metabolism of Pexidartinib can be increased when combined with Dexamethasone acetate.
Eslicarbazepine acetate The metabolism of Pexidartinib can be increased when combined with Eslicarbazepine acetate.
Asunaprevir The metabolism of Pexidartinib can be increased when combined with Asunaprevir.
Topiramate The metabolism of Pexidartinib can be increased when combined with Topiramate.
Rifabutin The metabolism of Pexidartinib can be increased when combined with Rifabutin.
Warfarin The metabolism of Pexidartinib can be increased when combined with Warfarin.
Felbamate The metabolism of Pexidartinib can be increased when combined with Felbamate.
Genistein The metabolism of Pexidartinib can be increased when combined with Genistein.
Oritavancin The metabolism of Pexidartinib can be increased when combined with Oritavancin.
Rufinamide The metabolism of Pexidartinib can be increased when combined with Rufinamide.
Glycerol phenylbutyrate The metabolism of Pexidartinib can be increased when combined with Glycerol phenylbutyrate.
Lesinurad The metabolism of Pexidartinib can be increased when combined with Lesinurad.
Pitolisant The metabolism of Pexidartinib can be increased when combined with Pitolisant.

Target Protein

Macrophage colony-stimulating factor 1 receptor CSF1R
Mast/stem cell growth factor receptor Kit KIT
Receptor-type tyrosine-protein kinase FLT3 FLT3
Platelet-derived growth factor receptor beta PDGFRB

Referensi & Sumber

Synthesis reference: Chen D, Zhang Y, Li J, Liu Y: Exploratory Process Development of Pexidartinib through the Tandem Tsuji–Trost Reaction and Heck Coupling. Synthesis. 2019 January 4;51(12):2564-2571. doi:10.1055/s-0037-1612421.
Artikel (PubMed)
  • PMID: 30002809
    Giustini N, Bernthal NM, Bukata SV, Singh AS: Tenosynovial giant cell tumor: case report of a patient effectively treated with pexidartinib (PLX3397) and review of the literature. Clin Sarcoma Res. 2018 Jul 10;8:14. doi: 10.1186/s13569-018-0101-2. eCollection 2018.
  • PMID: 31229240
    Tap WD, Gelderblom H, Palmerini E, Desai J, Bauer S, Blay JY, Alcindor T, Ganjoo K, Martin-Broto J, Ryan CW, Thomas DM, Peterfy C, Healey JH, van de Sande M, Gelhorn HL, Shuster DE, Wang Q, Yver A, Hsu HH, Lin PS, Tong-Starksen S, Stacchiotti S, Wagner AJ: Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial. Lancet. 2019 Jun 19. pii: S0140-6736(19)30764-0. doi: 10.1016/S0140-6736(19)30764-0.
  • PMID: 28716061
    Cannarile MA, Weisser M, Jacob W, Jegg AM, Ries CH, Ruttinger D: Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017 Jul 18;5(1):53. doi: 10.1186/s40425-017-0257-y.
  • PMID: 19443701
    Espinosa I, Beck AH, Lee CH, Zhu S, Montgomery KD, Marinelli RJ, Ganjoo KN, Nielsen TO, Gilks CB, West RB, van de Rijn M: Coordinate expression of colony-stimulating factor-1 and colony-stimulating factor-1-related proteins is associated with poor prognosis in gynecological and nongynecological leiomyosarcoma. Am J Pathol. 2009 Jun;174(6):2347-56. doi: 10.2353/ajpath.2009.081037. Epub 2009 May 14.
  • PMID: 22186992
    Hume DA, MacDonald KP: Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling. Blood. 2012 Feb 23;119(8):1810-20. doi: 10.1182/blood-2011-09-379214. Epub 2011 Dec 20.
  • PMID: 28210073
    Nielsen SR, Schmid MC: Macrophages as Key Drivers of Cancer Progression and Metastasis. Mediators Inflamm. 2017;2017:9624760. doi: 10.1155/2017/9624760. Epub 2017 Jan 22.
  • PMID: 28117416
    Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P: Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol. 2017 Jul;14(7):399-416. doi: 10.1038/nrclinonc.2016.217. Epub 2017 Jan 24.
  • PMID: 17527089
    Cupp JS, Miller MA, Montgomery KD, Nielsen TO, O'Connell JX, Huntsman D, van de Rijn M, Gilks CB, West RB: Translocation and expression of CSF1 in pigmented villonodular synovitis, tenosynovial giant cell tumor, rheumatoid arthritis and other reactive synovitides. Am J Surg Pathol. 2007 Jun;31(6):970-6. doi: 10.1097/PAS.0b013e31802b86f8.

Contoh Produk & Brand

Produk: 2 • International brands: 0
Produk
  • Turalio
    Capsule • 125 mg/1 • Oral • US • Approved
  • Turalio
    Capsule • 200 mg/1 • Oral • US • Approved

Sekuens Gen/Protein (FASTA)

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