Peringatan Keamanan

Data regarding overdoses of avapritinib are not readily available.^L40363

Avapritinib

DB15233

small molecule approved investigational

Deskripsi

Avapritinib, or BLU-285,^A189327 is a selective tyrosine kinase inhibitor of KIT and platelet derived growth factor receptor alpha indicated for the treatment of unresectable, metastatic gastrointestinal stromal tumors and advanced systemic mastocytosis.A189339,L40363 It is one of the first medications available for the treatment of multidrug resistant cancers.^A189327 Avapritinib shares a similar mechanism with ripretinib.

Avapritinib was granted FDA approval on 9 January 2020 ^L40363 and EMA approval on 24 September 2020.^L41464

Struktur Molekul 2D

Berat 498.57

Wujud solid

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

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

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) The half life of avapritinib is 32-57h.[L40363]

Volume Distribusi The mean apparent volume of distribution is 1200L.[L40363]

Klirens (Clearance) The mean apparent oral clearance of avapritinib is 19.5L/h.[L40363]

Absorpsi

A 300mg oral dose of avapritinib reaches a C_max of 813ng/mL with a T_max of 2.0-4.1h and an AUC of 15400h\*ng/mL.^L40363

Metabolisme

Avapritinib is metabolized mainly by CYP3A4 and CYP2C9 in vitro.^L40363 A 310mg oral dose is recovered as 49% unchanged drug, 35% hydroxy glucuronide metabolite, and 14% oxidatively deaminated metabolite.^L40363

Rute Eliminasi

Avapritinib is 70% eliminated in the feces with 11% as the unchanged drug and 18% eliminated in the urine with 0.23% as the unchanged drug.^L40363

Interaksi Makanan

3 Data

1. Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of avapritinib.
2. Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of avapritinib.
3. Take on an empty stomach. Take more than 1 hour before or 2 hours after a meal.

Interaksi Obat

416 Data

Fluvoxamine	The metabolism of Avapritinib can be decreased when combined with Fluvoxamine.
Troglitazone	The metabolism of Avapritinib can be decreased when combined with Troglitazone.
Fluoxetine	The metabolism of Avapritinib can be decreased when combined with Fluoxetine.
Nabilone	The metabolism of Nabilone can be decreased when combined with Avapritinib.
Imatinib	The metabolism of Avapritinib can be decreased when combined with Imatinib.
Mifepristone	The metabolism of Avapritinib can be decreased when combined with Mifepristone.
Felbamate	The metabolism of Avapritinib can be decreased when combined with Felbamate.
Sulfinpyrazone	The metabolism of Avapritinib can be decreased when combined with Sulfinpyrazone.
Iproniazid	The metabolism of Avapritinib can be decreased when combined with Iproniazid.
Medical Cannabis	The metabolism of Avapritinib can be decreased when combined with Medical Cannabis.
Valproic acid	The metabolism of Avapritinib can be decreased when combined with Valproic acid.
Quinidine	The metabolism of Avapritinib can be decreased when combined with Quinidine.
Dabrafenib	The serum concentration of Avapritinib can be decreased when it is combined with Dabrafenib.
Miconazole	The metabolism of Avapritinib can be decreased when combined with Miconazole.
Fluconazole	The metabolism of Avapritinib can be decreased when combined with Fluconazole.
Floxuridine	The metabolism of Avapritinib can be decreased when combined with Floxuridine.
Nicardipine	The metabolism of Avapritinib can be decreased when combined with Nicardipine.
Gemfibrozil	The metabolism of Avapritinib can be decreased when combined with Gemfibrozil.
Sulfaphenazole	The metabolism of Avapritinib can be decreased when combined with Sulfaphenazole.
Pitolisant	The serum concentration of Avapritinib can be decreased when it is combined with Pitolisant.
Metreleptin	The metabolism of Avapritinib can be increased when combined with Metreleptin.
Bosentan	The metabolism of Avapritinib can be increased when combined with Bosentan.
Peginterferon alfa-2b	The metabolism of Avapritinib can be increased when combined with Peginterferon alfa-2b.
Delafloxacin	The metabolism of Avapritinib can be increased when combined with Delafloxacin.
Valsartan	The metabolism of Avapritinib can be decreased when combined with Valsartan.
Torasemide	The metabolism of Avapritinib can be decreased when combined with Torasemide.
Diethylstilbestrol	The metabolism of Avapritinib can be decreased when combined with Diethylstilbestrol.
Sulfisoxazole	The metabolism of Avapritinib can be decreased when combined with Sulfisoxazole.
Sulfadiazine	The metabolism of Avapritinib can be decreased when combined with Sulfadiazine.
Progesterone	The metabolism of Avapritinib can be decreased when combined with Progesterone.
Cerivastatin	The metabolism of Avapritinib can be decreased when combined with Cerivastatin.
Teniposide	The metabolism of Avapritinib can be decreased when combined with Teniposide.
Cimetidine	The metabolism of Avapritinib can be decreased when combined with Cimetidine.
Fluorouracil	The metabolism of Avapritinib can be decreased when combined with Fluorouracil.
Zafirlukast	The metabolism of Avapritinib can be decreased when combined with Zafirlukast.
Sulfamethizole	The metabolism of Avapritinib can be decreased when combined with Sulfamethizole.
Medroxyprogesterone acetate	The metabolism of Avapritinib can be decreased when combined with Medroxyprogesterone acetate.
Amodiaquine	The metabolism of Avapritinib can be decreased when combined with Amodiaquine.
Oxandrolone	The metabolism of Avapritinib can be decreased when combined with Oxandrolone.
Simvastatin	The metabolism of Avapritinib can be decreased when combined with Simvastatin.
Nilutamide	The metabolism of Avapritinib can be decreased when combined with Nilutamide.
Epinephrine	The metabolism of Avapritinib can be decreased when combined with Epinephrine.
Paroxetine	The metabolism of Avapritinib can be decreased when combined with Paroxetine.
Modafinil	The metabolism of Avapritinib can be decreased when combined with Modafinil.
Tranylcypromine	The metabolism of Avapritinib can be decreased when combined with Tranylcypromine.
Clopidogrel	The metabolism of Avapritinib can be decreased when combined with Clopidogrel.
Phenylbutazone	The metabolism of Avapritinib can be decreased when combined with Phenylbutazone.
Sulfapyridine	The metabolism of Avapritinib can be decreased when combined with Sulfapyridine.
Ethanol	The metabolism of Avapritinib can be decreased when combined with Ethanol.
Metronidazole	The metabolism of Avapritinib can be decreased when combined with Metronidazole.
Isoniazid	The metabolism of Avapritinib can be decreased when combined with Isoniazid.
Sulfamethoxazole	The metabolism of Avapritinib can be decreased when combined with Sulfamethoxazole.
Glyburide	The metabolism of Avapritinib can be decreased when combined with Glyburide.
Felodipine	The metabolism of Avapritinib can be decreased when combined with Felodipine.
Probenecid	The metabolism of Avapritinib can be decreased when combined with Probenecid.
Fenofibrate	The metabolism of Avapritinib can be decreased when combined with Fenofibrate.
Promethazine	The metabolism of Avapritinib can be decreased when combined with Promethazine.
Fluvastatin	The metabolism of Avapritinib can be decreased when combined with Fluvastatin.
Leflunomide	The metabolism of Avapritinib can be decreased when combined with Leflunomide.
Sertraline	The metabolism of Avapritinib can be decreased when combined with Sertraline.
Atovaquone	The metabolism of Avapritinib can be decreased when combined with Atovaquone.
Cyclizine	The metabolism of Avapritinib can be decreased when combined with Cyclizine.
Flecainide	The metabolism of Avapritinib can be decreased when combined with Flecainide.
Ginkgo biloba	The metabolism of Avapritinib can be decreased when combined with Ginkgo biloba.
Pranlukast	The metabolism of Avapritinib can be decreased when combined with Pranlukast.
Etoricoxib	The metabolism of Avapritinib can be decreased when combined with Etoricoxib.
Genistein	The metabolism of Avapritinib can be decreased when combined with Genistein.
Topiroxostat	The metabolism of Avapritinib can be decreased when combined with Topiroxostat.
Doconexent	The metabolism of Avapritinib can be decreased when combined with Doconexent.
Estrone sulfate	The metabolism of Avapritinib can be decreased when combined with Estrone sulfate.
Tienilic acid	The metabolism of Avapritinib can be decreased when combined with Tienilic acid.
Dexloxiglumide	The metabolism of Avapritinib can be decreased when combined with Dexloxiglumide.
Clevidipine	The metabolism of Avapritinib can be decreased when combined with Clevidipine.
Noscapine	The metabolism of Avapritinib can be decreased when combined with Noscapine.
Sitaxentan	The metabolism of Avapritinib can be decreased when combined with Sitaxentan.
Armodafinil	The metabolism of Avapritinib can be decreased when combined with Armodafinil.
Etravirine	The metabolism of Avapritinib can be decreased when combined with Etravirine.
Avasimibe	The metabolism of Avapritinib can be decreased when combined with Avasimibe.
Agomelatine	The metabolism of Avapritinib can be decreased when combined with Agomelatine.
Seproxetine	The metabolism of Avapritinib can be decreased when combined with Seproxetine.
Sulfamoxole	The metabolism of Avapritinib can be decreased when combined with Sulfamoxole.
Vemurafenib	The metabolism of Avapritinib can be decreased when combined with Vemurafenib.
Regorafenib	The metabolism of Avapritinib can be decreased when combined with Regorafenib.
Ceritinib	The metabolism of Avapritinib can be decreased when combined with Ceritinib.
Lobeglitazone	The metabolism of Avapritinib can be decreased when combined with Lobeglitazone.
Manidipine	The metabolism of Avapritinib can be decreased when combined with Manidipine.
Isavuconazole	The metabolism of Avapritinib can be decreased when combined with Isavuconazole.
Diacerein	The metabolism of Avapritinib can be decreased when combined with Diacerein.
Triclabendazole	The metabolism of Avapritinib can be decreased when combined with Triclabendazole.
Benzbromarone	The metabolism of Avapritinib can be decreased when combined with Benzbromarone.
Rucaparib	The metabolism of Avapritinib can be decreased when combined with Rucaparib.
Methylene blue	The metabolism of Avapritinib can be decreased when combined with Methylene blue.
Pralsetinib	The metabolism of Avapritinib can be decreased when combined with Pralsetinib.
Rilpivirine	The metabolism of Avapritinib can be decreased when combined with Rilpivirine.
Diosmin	The metabolism of Avapritinib can be decreased when combined with Diosmin.
Sildenafil	The metabolism of Sildenafil can be decreased when combined with Avapritinib.
Ticlopidine	The metabolism of Avapritinib can be decreased when combined with Ticlopidine.
Olanzapine	The metabolism of Avapritinib can be decreased when combined with Olanzapine.
Valdecoxib	The metabolism of Valdecoxib can be decreased when combined with Avapritinib.
Oritavancin	The metabolism of Avapritinib can be decreased when combined with Oritavancin.

Target Protein

Platelet-derived growth factor receptor alpha PDGFRA

Mast/stem cell growth factor receptor Kit KIT

Referensi & Sumber

Artikel (PubMed)

PMID: 31117741
Wu CP, Lusvarghi S, Wang JC, Hsiao SH, Huang YH, Hung TH, Ambudkar SV: Avapritinib: A Selective Inhibitor of KIT and PDGFRalpha that Reverses ABCB1 and ABCG2-Mediated Multidrug Resistance in Cancer Cell Lines. Mol Pharm. 2019 Jul 1;16(7):3040-3052. doi: 10.1021/acs.molpharmaceut.9b00274. Epub 2019 Jun 4.
PMID: 31205499
Mazzocca A, Napolitano A, Silletta M, Spalato Ceruso M, Santini D, Tonini G, Vincenzi B: New frontiers in the medical management of gastrointestinal stromal tumours. Ther Adv Med Oncol. 2019 May 17;11:1758835919841946. doi: 10.1177/1758835919841946. eCollection 2019.

Link

Contoh Produk & Brand

Produk: 14 • International brands: 0

Produk

Ayvakit

Tablet, film coated • 25 mg/1 • Oral • US • Approved
Ayvakit

Tablet, film coated • 50 mg/1 • Oral • US • Approved
Ayvakit

Tablet, film coated • 100 mg/1 • Oral • US • Approved
Ayvakit

Tablet, film coated • 200 mg/1 • Oral • US • Approved
Ayvakit

Tablet, film coated • 300 mg/1 • Oral • US • Approved
Ayvakyt

Tablet • 25 mg • Oral • Canada • Approved
Ayvakyt

Tablet • 50 mg • Oral • Canada • Approved
Ayvakyt

Tablet • 100 mg • Oral • Canada • Approved

Menampilkan 8 dari 14 produk.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.