Peringatan Keamanan

No overdose experience has been reported with sparsentan. Doses up to 1600 mg/day and 400 mg/day have been given to healthy volunteers and patients, respectively. Overdose of sparsentan may result in decreased blood pressure. Provide standard supportive measures, as required, in case of an overdose. Since sparsentan is highly protein-bound, dyalisis may not be effective.^L45300 A 2-year rat carcinogenicity study where male and female mice received 0.7 and 26 times the AUC at the maximum recommended human dose (MRHD), respectively, found no evidence of increased incidence of neoplasia. A 26-week transgenic mouse study reported similar results. In vitro bacteria reverse mutation and chromosomal aberration assays and an in vivo rat micronucleus study did not find evidence of mutagenicity or clastogenicity for sparsentan. Sparsentan did not lead to an impairment of fertility in male or female rats and monkeys.^L45300

Sparsentan

DB12548

small molecule approved investigational

Deskripsi

Sparsentan is a dual antagonist of the endothelin type A receptor (ET_AR) and the angiotensin II (Ang II) type 1 receptor (AT₁R) with a similar affinity for both (9.3 nM for ET_AR and 0.8 nM for AT₁R).A257330,L45300 Sparsentan is first in its class and orally active, and was created by merging the structural elements of irbesartan, an AT₁R antagonist, and biphenylsulfonamide, an ET_AR antagonist.^A257330

In February 2023, the use of sparsentan to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression was approved by the FDA under accelerated approval based on reduction of proteinuria.L45300,L45315 In September 2024, it was granted full approval for an expanded indication.^L51419 Sparsentan was initially developed for the treatment of hypertension;^A257340 however, it has shown to be efficient in the reduction of proteinuria in patients with IgAN and focal segmental glomerulosclerosis (FSGS).A257325,A257335,L45310 Compared to irbesartan, sparsentan reduces proteinuria to a greater extent. Furthermore, it is the first non-immunosuppressive therapy for the reduction of proteinuria in IgAN.^L45315 The use of sparsentan may cause hepatotoxicity and embryo-fetal toxicity.^L45300

On April 24, 2024, sparsentan was granted conditional marketing authorization by the European Commission for the treatment of adults with primary IgAN.^L51559

Struktur Molekul 2D

Berat 592.76

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) Sparsentan has an estimated half-life of 9.6 hours at steady state.[L45300]

Volume Distribusi At the approved recommended dosage, sparsentan has an apparent volume of distribution at steady state of 61.4 L.[L45300]

Klirens (Clearance) Sparsentan has a time-dependent clearance, possibly due to it inducing its own metabolism over time. Following the initial 400 mg dose, sparsentan has an apparent clearance of 3.88 L/h. At steady state, the apparent clearance increases to 5.11 L/h.[L45300]

Absorpsi

Following administration of single doses of 200-1600 mg, the C_max and AUC of sparsentan increase in a less than dose-proportional manner. Sparsentan has time-dependent pharmacokinetics, possibly due to it inducing its own metabolism over time, and at the approved recommended dosage, it reaches steady-state plasma levels within 7 days. Following a single oral dose of 400 mg, the C_max, AUC and median time to peak plasma concentration of sparsentan are 6.97 ?g/mL, 83 ?g×h/mL, and 3 hours, respectively. Following daily doses of 400 mg sparsentan, the steady-state C_max is 6.47 ?g/mL, and the AUC is 63.6 ?g×h/mL. The administration of a single oral dose (800 mg) of sparsentan with a high-fat, high-calorie meal (1000 kcal, 50% fat) increased the AUC and C_max by 22% and 108%, respectively. With a single 200 mg dose, a high-fat, high-calorie meal did not have a clinically significant effect on sparsentan pharmacokinetics.^L45300

Metabolisme

Sparsentan is mainly metabolized by cytochrome P450 3A.^L45300

Rute Eliminasi

Sparsentan is mainly excreted through feces and urine. In healthy subjects given a single dose (400 mg) of radiolabeled sparsentan, approximately 80% of the dose was recovered in feces (9% unchanged) and 2% in urine (negligible amount unchanged). Within a 10-day collection period, 82% of the dosed radioactivity was recovered.^L45300

Interaksi Makanan

1 Data

1. Take before a meal. Sparsentan AUC and Cmax increase following the administration of a high fat, high calorie meal. Advise patients to take the full daily dose with water prior to the morning or evening meal. Maintain the same dosing pattern in relationship to meals.

Interaksi Obat

764 Data

Aliskiren	The risk or severity of adverse effects can be increased when Aliskiren is combined with Sparsentan.
Canagliflozin	The risk or severity of hypotension, hyperkalemia, and reduced intravascular volume can be increased when Canagliflozin is combined with Sparsentan.
Drospirenone	The risk or severity of hyperkalemia can be increased when Sparsentan is combined with Drospirenone.
Eplerenone	The risk or severity of hyperkalemia can be increased when Eplerenone is combined with Sparsentan.
Ardeparin	The risk or severity of hyperkalemia can be increased when Ardeparin is combined with Sparsentan.
Heparin	The risk or severity of hyperkalemia can be increased when Heparin is combined with Sparsentan.
Enoxaparin	The risk or severity of hyperkalemia can be increased when Enoxaparin is combined with Sparsentan.
Sulodexide	The risk or severity of hyperkalemia can be increased when Sulodexide is combined with Sparsentan.
Semuloparin	The risk or severity of hyperkalemia can be increased when Semuloparin is combined with Sparsentan.
Danaparoid	The risk or severity of hyperkalemia can be increased when Danaparoid is combined with Sparsentan.
Dalteparin	The risk or severity of hyperkalemia can be increased when Dalteparin is combined with Sparsentan.
Tinzaparin	The risk or severity of hyperkalemia can be increased when Tinzaparin is combined with Sparsentan.
Nadroparin	The risk or severity of hyperkalemia can be increased when Nadroparin is combined with Sparsentan.
Bemiparin	The risk or severity of hyperkalemia can be increased when Bemiparin is combined with Sparsentan.
Reviparin	The risk or severity of hyperkalemia can be increased when Reviparin is combined with Sparsentan.
Parnaparin	The risk or severity of hyperkalemia can be increased when Parnaparin is combined with Sparsentan.
Methyclothiazide	Methyclothiazide may increase the hypotensive and Electrolyte Disturbance activities of Sparsentan.
Bendroflumethiazide	Bendroflumethiazide may increase the hypotensive and Electrolyte Disturbance activities of Sparsentan.
Benzthiazide	Benzthiazide may increase the hypotensive and Electrolyte Disturbance activities of Sparsentan.
Cyclothiazide	Cyclothiazide may increase the hypotensive and Electrolyte Disturbance activities of Sparsentan.
Hydroflumethiazide	Hydroflumethiazide may increase the hypotensive and Electrolyte Disturbance activities of Sparsentan.
Chlorothiazide	Chlorothiazide may increase the hypotensive and Electrolyte Disturbance activities of Sparsentan.
Hydrochlorothiazide	Hydrochlorothiazide may increase the hypotensive and Electrolyte Disturbance activities of Sparsentan.
Trichlormethiazide	Trichlormethiazide may increase the hypotensive and Electrolyte Disturbance activities of Sparsentan.
Polythiazide	Polythiazide may increase the hypotensive and Electrolyte Disturbance activities of Sparsentan.
Mebutizide	Mebutizide may increase the hypotensive and Electrolyte Disturbance activities of Sparsentan.
Cyclopenthiazide	Cyclopenthiazide may increase the hypotensive and Electrolyte Disturbance activities of Sparsentan.
Buthiazide	Buthiazide may increase the hypotensive and Electrolyte Disturbance activities of Sparsentan.
Lithium hydroxide	The serum concentration of Lithium hydroxide can be increased when it is combined with Sparsentan.
Lithium citrate	The serum concentration of Lithium citrate can be increased when it is combined with Sparsentan.
Lithium carbonate	The serum concentration of Lithium carbonate can be increased when it is combined with Sparsentan.
Tolvaptan	The risk or severity of hyperkalemia can be increased when Tolvaptan is combined with Sparsentan.
Trimethoprim	The risk or severity of hyperkalemia can be increased when Trimethoprim is combined with Sparsentan.
Ciprofloxacin	The risk or severity of hyperkalemia can be increased when Sparsentan is combined with Ciprofloxacin.
Cyclosporine	The risk or severity of hyperkalemia can be increased when Sparsentan is combined with Cyclosporine.
Nicorandil	The risk or severity of hyperkalemia can be increased when Nicorandil is combined with Sparsentan.
Icosapent	The risk or severity of adverse effects can be increased when Icosapent is combined with Sparsentan.
Indomethacin	The risk or severity of adverse effects can be increased when Indomethacin is combined with Sparsentan.
Nabumetone	The risk or severity of adverse effects can be increased when Nabumetone is combined with Sparsentan.
Ketorolac	The therapeutic efficacy of Sparsentan can be decreased when used in combination with Ketorolac.
Tenoxicam	The risk or severity of adverse effects can be increased when Tenoxicam is combined with Sparsentan.
Celecoxib	The risk or severity of adverse effects can be increased when Celecoxib is combined with Sparsentan.
Tolmetin	The risk or severity of adverse effects can be increased when Tolmetin is combined with Sparsentan.
Rofecoxib	The risk or severity of adverse effects can be increased when Rofecoxib is combined with Sparsentan.
Piroxicam	The risk or severity of adverse effects can be increased when Piroxicam is combined with Sparsentan.
Fenoprofen	The risk or severity of adverse effects can be increased when Fenoprofen is combined with Sparsentan.
Valdecoxib	The risk or severity of adverse effects can be increased when Valdecoxib is combined with Sparsentan.
Diclofenac	The risk or severity of adverse effects can be increased when Diclofenac is combined with Sparsentan.
Sulindac	The risk or severity of adverse effects can be increased when Sulindac is combined with Sparsentan.
Flurbiprofen	The risk or severity of adverse effects can be increased when Flurbiprofen is combined with Sparsentan.
Etodolac	The risk or severity of adverse effects can be increased when Etodolac is combined with Sparsentan.
Mefenamic acid	The risk or severity of adverse effects can be increased when Mefenamic acid is combined with Sparsentan.
Naproxen	The risk or severity of adverse effects can be increased when Naproxen is combined with Sparsentan.
Sulfasalazine	The risk or severity of adverse effects can be increased when Sulfasalazine is combined with Sparsentan.
Phenylbutazone	The risk or severity of adverse effects can be increased when Phenylbutazone is combined with Sparsentan.
Meloxicam	The risk or severity of adverse effects can be increased when Meloxicam is combined with Sparsentan.
Carprofen	The risk or severity of adverse effects can be increased when Carprofen is combined with Sparsentan.
Diflunisal	The risk or severity of adverse effects can be increased when Diflunisal is combined with Sparsentan.
Salicylic acid	The risk or severity of adverse effects can be increased when Salicylic acid is combined with Sparsentan.
Meclofenamic acid	The risk or severity of adverse effects can be increased when Meclofenamic acid is combined with Sparsentan.
Acetylsalicylic acid	The risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Sparsentan.
Oxaprozin	The risk or severity of adverse effects can be increased when Oxaprozin is combined with Sparsentan.
Ketoprofen	The risk or severity of adverse effects can be increased when Ketoprofen is combined with Sparsentan.
Balsalazide	The risk or severity of adverse effects can be increased when Balsalazide is combined with Sparsentan.
Ibuprofen	The risk or severity of adverse effects can be increased when Ibuprofen is combined with Sparsentan.
Lumiracoxib	The risk or severity of adverse effects can be increased when Lumiracoxib is combined with Sparsentan.
Magnesium salicylate	The risk or severity of adverse effects can be increased when Magnesium salicylate is combined with Sparsentan.
Salsalate	The risk or severity of adverse effects can be increased when Salsalate is combined with Sparsentan.
Choline magnesium trisalicylate	The risk or severity of adverse effects can be increased when Choline magnesium trisalicylate is combined with Sparsentan.
Antrafenine	The risk or severity of adverse effects can be increased when Antrafenine is combined with Sparsentan.
Aminophenazone	The risk or severity of adverse effects can be increased when Aminophenazone is combined with Sparsentan.
Antipyrine	The risk or severity of adverse effects can be increased when Antipyrine is combined with Sparsentan.
Tiaprofenic acid	The risk or severity of adverse effects can be increased when Tiaprofenic acid is combined with Sparsentan.
Etoricoxib	The risk or severity of adverse effects can be increased when Etoricoxib is combined with Sparsentan.
Taxifolin	The risk or severity of adverse effects can be increased when Taxifolin is combined with Sparsentan.
Oxyphenbutazone	The risk or severity of adverse effects can be increased when Oxyphenbutazone is combined with Sparsentan.
Niflumic acid	The risk or severity of adverse effects can be increased when Niflumic acid is combined with Sparsentan.
Licofelone	The risk or severity of adverse effects can be increased when Licofelone is combined with Sparsentan.
Nimesulide	The risk or severity of adverse effects can be increased when Nimesulide is combined with Sparsentan.
Benoxaprofen	The risk or severity of adverse effects can be increased when Benoxaprofen is combined with Sparsentan.
Zomepirac	The risk or severity of adverse effects can be increased when Zomepirac is combined with Sparsentan.
Cimicoxib	The risk or severity of adverse effects can be increased when Cimicoxib is combined with Sparsentan.
Lornoxicam	The risk or severity of adverse effects can be increased when Lornoxicam is combined with Sparsentan.
Aceclofenac	The risk or severity of adverse effects can be increased when Aceclofenac is combined with Sparsentan.
Zaltoprofen	The risk or severity of adverse effects can be increased when Zaltoprofen is combined with Sparsentan.
Azapropazone	The risk or severity of adverse effects can be increased when Azapropazone is combined with Sparsentan.
Parecoxib	The risk or severity of adverse effects can be increased when Parecoxib is combined with Sparsentan.
Salicylamide	The risk or severity of adverse effects can be increased when Salicylamide is combined with Sparsentan.
Kebuzone	The risk or severity of adverse effects can be increased when Kebuzone is combined with Sparsentan.
Isoxicam	The risk or severity of adverse effects can be increased when Isoxicam is combined with Sparsentan.
Indoprofen	The risk or severity of adverse effects can be increased when Indoprofen is combined with Sparsentan.
Ibuproxam	The risk or severity of adverse effects can be increased when Ibuproxam is combined with Sparsentan.
Floctafenine	The risk or severity of adverse effects can be increased when Floctafenine is combined with Sparsentan.
Fenbufen	The risk or severity of adverse effects can be increased when Fenbufen is combined with Sparsentan.
Etofenamate	The risk or severity of adverse effects can be increased when Etofenamate is combined with Sparsentan.
Epirizole	The risk or severity of adverse effects can be increased when Epirizole is combined with Sparsentan.
Benzydamine	The risk or severity of adverse effects can be increased when Benzydamine is combined with Sparsentan.
Loxoprofen	The risk or severity of adverse effects can be increased when Loxoprofen is combined with Sparsentan.
Dexibuprofen	The risk or severity of adverse effects can be increased when Dexibuprofen is combined with Sparsentan.
Dexketoprofen	The risk or severity of adverse effects can be increased when Dexketoprofen is combined with Sparsentan.

Target Protein

Endothelin-1 receptor EDNRA

Type-1 angiotensin II receptor AGTR1

Type-2 angiotensin II receptor AGTR2

Referensi & Sumber

Artikel (PubMed)

PMID: 29142983
Komers R, Gipson DS, Nelson P, Adler S, Srivastava T, Derebail VK, Meyers KE, Pergola P, MacNally ME, Hunt JL, Shih A, Trachtman H: Efficacy and Safety of Sparsentan Compared With Irbesartan in Patients With Primary Focal Segmental Glomerulosclerosis: Randomized, Controlled Trial Design (DUET). Kidney Int Rep. 2017 Mar 4;2(4):654-664. doi: 10.1016/j.ekir.2017.02.019. eCollection 2017 Jul.
PMID: 29947527
Davenport AP, Kuc RE, Southan C, Maguire JJ: New drugs and emerging therapeutic targets in the endothelin signaling pathway and prospects for personalized precision medicine. Physiol Res. 2018 Jun 27;67(Suppl 1):S37-S54. doi: 10.33549/physiolres.933872.
PMID: 32274453
Komers R, Diva U, Inrig JK, Loewen A, Trachtman H, Rote WE: Study Design of the Phase 3 Sparsentan Versus Irbesartan (DUPLEX) Study in Patients With Focal Segmental Glomerulosclerosis. Kidney Int Rep. 2020 Jan 8;5(4):494-502. doi: 10.1016/j.ekir.2019.12.017. eCollection 2020 Apr.
PMID: 15634011
Murugesan N, Gu Z, Fadnis L, Tellew JE, Baska RA, Yang Y, Beyer SM, Monshizadegan H, Dickinson KE, Valentine MT, Humphreys WG, Lan SJ, Ewing WR, Carlson KE, Kowala MC, Zahler R, Macor JE: Dual angiotensin II and endothelin A receptor antagonists: synthesis of 2'-substituted N-3-isoxazolyl biphenylsulfonamides with improved potency and pharmacokinetics. J Med Chem. 2005 Jan 13;48(1):171-9. doi: 10.1021/jm049548x.

Link

Contoh Produk & Brand

Produk: 2 • International brands: 1

Produk

Filspari

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

Tablet, film coated • 400 mg/1 • Oral • US • Approved

International Brands

Filspari — Travere Therapeutics

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.