Peringatan Keamanan

An overdose of vadadustat may lead to extensions of the pharmacologic effects, such as increased hemoglobin levels and secondary polycythemia. In case of overdose, patients should be managed with clinically appropriate measures, such as dose reduction or treatment discontinuation. Patients should be carefully monitored and treated as clinically indicated. Approximately 16% of the vadadustat dose is removed by dialysis.^L46936

Vadadustat

DB12255

small molecule approved investigational

Deskripsi

One of the most common symptoms of advanced renal disease is anemia, caused primarily by the inability of the kidney to respond to anemic conditions with a corresponding increase in erythropoietin (EPO) production.^A244165 The treatment of anemia associated with chronic kidney disease (CKD) has traditionally involved the administration of exogenous erythropoiesis-stimulating agents (ESAs), such as darbepoetin alfa, to counter the decrease in endogenous EPO production. While efficacious, the overuse of ESAs has been associated with cardiovascular complications, progression of CKD, and increases in overall mortality.^A244165

A relatively new and alternative treatment option for patients with anemia associated with CKD is the use of small molecule inhibitors of hypoxia-inducible factor prolyl-hydroxylase (HIF-PH). These agents inhibit prolyl-hydroxylase domain oxygen sensors, mimicking hypoxic conditions and activating hypoxia-inducible factors. These transcription factors serve a multitude of roles, including the stimulation of erythropoiesis.^A244165

Vadadustat is an orally administered inhibitor of HIF-PH with a safety and efficacy profile non-inferior to darbepoetin alfa for the treatment of anemia in patients with CKD undergoing dialysis.A244145,A244155 It was first approved in Japan in 2020,^L50371 and in April 2023, it was approved by the EMA for the treatment of symptomatic anemia associated with CKD in adults on chronic maintenance dialysis.L39610,L46936,L46951 Vadadustat was approved by the FDA in March 2024.^L50371

Struktur Molekul 2D

Berat 306.7

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) In patients with dialysis-dependent chronic kidney disease, the half-life of vadadustat was 9.2 hours.[L46936]

Volume Distribusi The apparent volume of distribution of vadadustat in patients with chronic kidney disease is 11.6 L.[L46936]

Klirens (Clearance) In healthy subjects given a single dose of 300 mg of vadadustat, the apparent total body clearance ranged from 1.7 L/h to 1.9 L/h.[A260056] In patients with chronic kidney disease, the clearance of vadadustat is 0.8 L/h.[L46946]

Absorpsi

Following single and repeated doses, vadadustat is rapidly absorbed. The T_max of vadadustat ranges between 2 and 3 hr. No significant accumulation was detected in healthy subjects given repeated doses of vadadustat. Compared to fasted conditions, the administration of a 450 mg vadadustat tablet with a standard high-fat meal decreased the C_max and AUC by 27% and 6%, respectively. Vadadustat may be taken with or without food. The mean blood-to-plasma ratio of vadadustat went from 0.50 to 0.55, suggesting that the sequestration of vadadustat into red blood cells is minimal.^L46936

Metabolisme

Vadadustat is mainly metabolized by UDP-glucuronosyltransferase (UGT) enzymes, forming O-glucuronide conjugates via direct glucuronidation. The metabolism of vadadustat via cytochrome P450s (CYPs) is minimal. The major metabolite of vadadustat is vadadustat-O-glucuronide, which has 15% of the AUC of plasma radioactivity, and it is catalyzed by multiple UGT enzymes, including UGT1A1, UGT1A7, UGT1A8 and UGT1A9. Vadadustat acyl glucuronide is a minor metabolite with 0.047% of the total radioactivity in plasma. None of the vadadustat metabolites are active.^L46936

Rute Eliminasi

In healthy subjects given a single dose of 650 mg of radiolabelled vadadustat, 85.9% of the dose was recovered, with 58.9% appearing in urine and 26.9% in feces. Small amounts of the unchanged form of vadadustat are excreted in urine and feces (<1% and 9%, respectively).^L46936

Interaksi Makanan

1 Data

1. Take with or without food. The administration of a standard high-fat meal decreases the AUC of vadadustat by 6%, relative to fasted conditions; however, it may be administered with or without food.

Interaksi Obat

1107 Data

Iron Dextran	The serum concentration of Vadadustat can be decreased when it is combined with Iron Dextran.
Iron	The serum concentration of Vadadustat can be decreased when it is combined with Iron.
Prussian blue	The serum concentration of Vadadustat can be decreased when it is combined with Prussian blue.
Iron sucrose	The serum concentration of Vadadustat can be decreased when it is combined with Iron sucrose.
Ferric pyrophosphate	The serum concentration of Vadadustat can be decreased when it is combined with Ferric pyrophosphate.
Ferric ammonium citrate	The serum concentration of Vadadustat can be decreased when it is combined with Ferric ammonium citrate.
Ferumoxsil	The serum concentration of Vadadustat can be decreased when it is combined with Ferumoxsil.
Ferumoxides	The serum concentration of Vadadustat can be decreased when it is combined with Ferumoxides.
Ferric sulfate	The serum concentration of Vadadustat can be decreased when it is combined with Ferric sulfate.
Ferrous bisglycinate	The serum concentration of Vadadustat can be decreased when it is combined with Ferrous bisglycinate.
Gleptoferron	The serum concentration of Vadadustat can be decreased when it is combined with Gleptoferron.
Perflubutane	The serum concentration of Vadadustat can be decreased when it is combined with Perflubutane.
Ferrous sulfate anhydrous	The serum concentration of Vadadustat can be decreased when it is combined with Ferrous sulfate anhydrous.
Sodium feredetate	The serum concentration of Vadadustat can be decreased when it is combined with Sodium feredetate.
Ferric hydroxide	The serum concentration of Vadadustat can be decreased when it is combined with Ferric hydroxide.
Ferric cation	The serum concentration of Vadadustat can be decreased when it is combined with Ferric cation.
Ferrous gluconate	The serum concentration of Vadadustat can be decreased when it is combined with Ferrous gluconate.
Ferrous succinate	The serum concentration of Vadadustat can be decreased when it is combined with Ferrous succinate.
Ferrous fumarate	The serum concentration of Vadadustat can be decreased when it is combined with Ferrous fumarate.
Tetraferric tricitrate decahydrate	The serum concentration of Vadadustat can be decreased when it is combined with Tetraferric tricitrate decahydrate.
Ferric oxyhydroxide	The serum concentration of Vadadustat can be decreased when it is combined with Ferric oxyhydroxide.
Ferric maltol	The serum concentration of Vadadustat can be decreased when it is combined with Ferric maltol.
Iron polymaltose	The serum concentration of Vadadustat can be decreased when it is combined with Iron polymaltose.
Calcium chloride	The serum concentration of Vadadustat can be decreased when it is combined with Calcium chloride.
Calcium carbonate	The serum concentration of Vadadustat can be decreased when it is combined with Calcium carbonate.
Calcium citrate	The serum concentration of Vadadustat can be decreased when it is combined with Calcium citrate.
Calcium Phosphate	The serum concentration of Vadadustat can be decreased when it is combined with Calcium Phosphate.
Calcium silicate	The serum concentration of Vadadustat can be decreased when it is combined with Calcium silicate.
Calcium phosphate dihydrate	The serum concentration of Vadadustat can be decreased when it is combined with Calcium phosphate dihydrate.
Magnesium sulfate	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium sulfate.
Magnesium oxide	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium oxide.
Magnesium salicylate	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium salicylate.
Magaldrate	The serum concentration of Vadadustat can be decreased when it is combined with Magaldrate.
Magnesium hydroxide	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium hydroxide.
Magnesium trisilicate	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium trisilicate.
Magnesium chloride	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium chloride.
Magnesium carbonate	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium carbonate.
Talc	The serum concentration of Vadadustat can be decreased when it is combined with Talc.
Magnesium citrate	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium citrate.
Magnesium silicate	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium silicate.
Hydrotalcite	The serum concentration of Vadadustat can be decreased when it is combined with Hydrotalcite.
Magnesium aspartate	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium aspartate.
Magnesium peroxide	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium peroxide.
Magnesium gluconate	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium gluconate.
Magnesium orotate	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium orotate.
Magnesium	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium.
Magnesium levulinate	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium levulinate.
Magnesium lactate	The serum concentration of Vadadustat can be decreased when it is combined with Magnesium lactate.
Sucralfate	The serum concentration of Vadadustat can be decreased when it is combined with Sucralfate.
Bentoquatam	The serum concentration of Vadadustat can be decreased when it is combined with Bentoquatam.
Aluminium	The serum concentration of Vadadustat can be decreased when it is combined with Aluminium.
Kaolin	The serum concentration of Vadadustat can be decreased when it is combined with Kaolin.
Aluminum hydroxide	The serum concentration of Vadadustat can be decreased when it is combined with Aluminum hydroxide.
Potassium alum	The serum concentration of Vadadustat can be decreased when it is combined with Potassium alum.
Aluminum chloride	The serum concentration of Vadadustat can be decreased when it is combined with Aluminum chloride.
Aluminum sesquichlorohydrate	The serum concentration of Vadadustat can be decreased when it is combined with Aluminum sesquichlorohydrate.
Aluminum sulfate	The serum concentration of Vadadustat can be decreased when it is combined with Aluminum sulfate.
Bentonite	The serum concentration of Vadadustat can be decreased when it is combined with Bentonite.
Aluminum oxide	The serum concentration of Vadadustat can be decreased when it is combined with Aluminum oxide.
Aluminum chlorohydrate	The serum concentration of Vadadustat can be decreased when it is combined with Aluminum chlorohydrate.
Aluminium acetoacetate	The serum concentration of Vadadustat can be decreased when it is combined with Aluminium acetoacetate.
Aluminium glycinate	The serum concentration of Vadadustat can be decreased when it is combined with Aluminium glycinate.
Aloglutamol	The serum concentration of Vadadustat can be decreased when it is combined with Aloglutamol.
Montmorillonite	The serum concentration of Vadadustat can be decreased when it is combined with Montmorillonite.
Aluminium phosphate	The serum concentration of Vadadustat can be decreased when it is combined with Aluminium phosphate.
Dihydroxyaluminum sodium carbonate	The serum concentration of Vadadustat can be decreased when it is combined with Dihydroxyaluminum sodium carbonate.
Aspartame	The serum concentration of Vadadustat can be increased when it is combined with Aspartame.
Pravastatin	The serum concentration of Vadadustat can be increased when it is combined with Pravastatin.
Pantoprazole	The serum concentration of Vadadustat can be increased when it is combined with Pantoprazole.
Cefotiam	The serum concentration of Vadadustat can be increased when it is combined with Cefotiam.
Liothyronine	The serum concentration of Vadadustat can be increased when it is combined with Liothyronine.
Conjugated estrogens	The serum concentration of Vadadustat can be increased when it is combined with Conjugated estrogens.
Valproic acid	The serum concentration of Vadadustat can be increased when it is combined with Valproic acid.
Indomethacin	The serum concentration of Vadadustat can be increased when it is combined with Indomethacin.
Aminohippuric acid	The serum concentration of Vadadustat can be increased when it is combined with Aminohippuric acid.
Lansoprazole	The serum concentration of Vadadustat can be increased when it is combined with Lansoprazole.
Cefalotin	The serum concentration of Vadadustat can be increased when it is combined with Cefalotin.
Tenoxicam	The serum concentration of Vadadustat can be increased when it is combined with Tenoxicam.
Cefotaxime	The serum concentration of Vadadustat can be increased when it is combined with Cefotaxime.
Zidovudine	The serum concentration of Vadadustat can be increased when it is combined with Zidovudine.
Cimetidine	The serum concentration of Vadadustat can be increased when it is combined with Cimetidine.
Guanidine	The serum concentration of Vadadustat can be increased when it is combined with Guanidine.
Piroxicam	The serum concentration of Vadadustat can be increased when it is combined with Piroxicam.
Methotrexate	The serum concentration of Vadadustat can be increased when it is combined with Methotrexate.
Cephalexin	The serum concentration of Vadadustat can be increased when it is combined with Cephalexin.
Enalapril	The serum concentration of Vadadustat can be increased when it is combined with Enalapril.
Diclofenac	The serum concentration of Vadadustat can be increased when it is combined with Diclofenac.
Oxytetracycline	The serum concentration of Vadadustat can be increased when it is combined with Oxytetracycline.
Linezolid	The serum concentration of Vadadustat can be increased when it is combined with Linezolid.
Leucovorin	The serum concentration of Vadadustat can be increased when it is combined with Leucovorin.
Latanoprost	The serum concentration of Vadadustat can be increased when it is combined with Latanoprost.
Furosemide	The serum concentration of Vadadustat can be increased when it is combined with Furosemide.
Esomeprazole	The serum concentration of Vadadustat can be increased when it is combined with Esomeprazole.
Tetracycline	The serum concentration of Vadadustat can be increased when it is combined with Tetracycline.
Acyclovir	The serum concentration of Vadadustat can be increased when it is combined with Acyclovir.
Phenylbutazone	The serum concentration of Vadadustat can be increased when it is combined with Phenylbutazone.
Cefaclor	The serum concentration of Vadadustat can be increased when it is combined with Cefaclor.
Bumetanide	The serum concentration of Vadadustat can be increased when it is combined with Bumetanide.
Quinidine	The serum concentration of Vadadustat can be increased when it is combined with Quinidine.
Dinoprostone	The serum concentration of Vadadustat can be increased when it is combined with Dinoprostone.

Target Protein

Egl nine homolog 1 EGLN1

Prolyl hydroxylase EGLN2 EGLN2

Prolyl hydroxylase EGLN3 EGLN3

Hypoxia-inducible factor 1-alpha HIF1A

Endothelial PAS domain-containing protein 1 EPAS1

Referensi & Sumber

Synthesis reference: Shengde, W., et al. (2012). Prolyl hydroxylase inhibitors and methods of use (U.S. Patent No. US 8,323,671 B2). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/3d/62/ce/4a3024a944d334/US8323671.pdf

Artikel (PubMed)

PMID: 33913638
Eckardt KU, Agarwal R, Aswad A, Awad A, Block GA, Bacci MR, Farag YMK, Fishbane S, Hubert H, Jardine A, Khawaja Z, Koury MJ, Maroni BJ, Matsushita K, McCullough PA, Lewis EF, Luo W, Parfrey PS, Pergola P, Sarnak MJ, Spinowitz B, Tumlin J, Vargo DL, Walters KA, Winkelmayer WC, Wittes J, Zwiech R, Chertow GM: Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis. N Engl J Med. 2021 Apr 29;384(17):1601-1612. doi: 10.1056/NEJMoa2025956.
PMID: 33650630
Nangaku M, Kondo K, Ueta K, Kokado Y, Kaneko G, Matsuda H, Kawaguchi Y, Komatsu Y: Efficacy and safety of vadadustat compared with darbepoetin alfa in Japanese anemic patients on hemodialysis: a Phase 3, multicenter, randomized, double-blind study. Nephrol Dial Transplant. 2021 Aug 27;36(9):1731-1741. doi: 10.1093/ndt/gfab055.
PMID: 31477256
Sanghani NS, Haase VH: Hypoxia-Inducible Factor Activators in Renal Anemia: Current Clinical Experience. Adv Chronic Kidney Dis. 2019 Jul;26(4):253-266. doi: 10.1053/j.ackd.2019.04.004.
PMID: 35172045
Paulson SK, Martinez J, Sawant R, Burke SK, Chavan A: Effect of Phosphate Binders and a Dietary Iron Supplement on the Pharmacokinetics of a Single Dose of Vadadustat in Healthy Adults. Clin Pharmacol Drug Dev. 2022 Apr;11(4):475-485. doi: 10.1002/cpdd.1033. Epub 2022 Feb 16.

Link

Contoh Produk & Brand

Produk: 9 • International brands: 1

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International Brands

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Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.