Peringatan Keamanan

According to prescribing information, aprocitentan has been administered in single doses up to 600 mg, and as multiple doses of up to 100 mg daily, in healthy subjects (48- and 8-fold the recommended dose, respectively).L50266 Observed symptoms of overdosage included headache, nasal congestion, nausea, and upper respiratory tract infection. In the event of an overdose, standard supportive treatment should be employed as clinically indicated. As aprocitentan is highly protein-bound, dialysis is unlikely to be effective.L50266

Aprocitentan

DB15059

small molecule approved investigational

Deskripsi

Aprocitentan is a dual antagonist of endothelin receptors A and B used for treatment-resistant hypertension. It is the active metabolite of macitentan.

Approximately 10-15% of patients with hypertension have resistant hypertension, defined as uncontrolled high blood pressure despite the combined use of a renin-angiotensin system blocker, a calcium channel blocker, and a diuretic at maximally tolerated doses.A263386 Patients with resistant hypertension are at an increased risk of cardiovascular and renal eventsA263386 and have traditionally had limited additional treatment options. Endothelin receptor antagonism provides a novel therapeutic pathway for the management of patients with resistant hypertension.A263386,L50261

Aprocitentan was approved by the FDA in March 2024 for the treatment of hypertension in patients inadequately controlled with standard therapy.L50261 It was the first antihypertensive employing a novel mechanism to be approved in almost 40 years.L50261

Struktur Molekul 2D

Berat 546.19
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 of aprocitentan is approximately 41 hours.[L50266]
Volume Distribusi The apparent volume of distribution of aprocitentan is approximately 20 L.[L50266]
Klirens (Clearance) The apparent clearance of aprocitentan is approximately 0.3 L/h.[L50266]

Absorpsi

The absolute oral bioavailability of aprocitentan is unknown.L50266 The mean Cmax and AUC0-tau following a single oral dose of 25mg are approximately 1.3 mcg/mL and 23 mcg.h/mL, respectively, with a Tmax between 4-5 hours.L50266

Metabolisme

Aprocitentan is primarily metabolized by UGT1A1- and UGT2B7-mediated N-glucosidation and non-enzymatic hydrolysis.L50266,A263441

Rute Eliminasi

Following the administration of a single radiolabeled dose of aprocitentan, approximately 52% of the dose was eliminated via urine (0.2% unchanged) and 25% via feces (6.8% unchanged).L50266

Interaksi Makanan

1 Data
  • 1. Take with or without food. Co-administration with food does not appear to alter the pharmacokinetics of aprocitentan to a clinically significant extent.

Interaksi Obat

676 Data
Nelfinavir The metabolism of Aprocitentan can be increased when combined with Nelfinavir.
Phenytoin The metabolism of Aprocitentan can be increased when combined with Phenytoin.
Desogestrel The metabolism of Aprocitentan can be increased when combined with Desogestrel.
Zidovudine The metabolism of Aprocitentan can be increased when combined with Zidovudine.
Ritonavir The metabolism of Aprocitentan can be increased when combined with Ritonavir.
Lamotrigine The metabolism of Aprocitentan can be increased when combined with Lamotrigine.
Carbamazepine The metabolism of Aprocitentan can be increased when combined with Carbamazepine.
Efavirenz The metabolism of Aprocitentan can be increased when combined with Efavirenz.
Primidone The metabolism of Aprocitentan can be increased when combined with Primidone.
Tipranavir The metabolism of Aprocitentan can be increased when combined with Tipranavir.
Ethinylestradiol The metabolism of Aprocitentan can be increased when combined with Ethinylestradiol.
Rifampin The metabolism of Aprocitentan can be increased when combined with Rifampicin.
Phenobarbital The metabolism of Aprocitentan can be increased when combined with Phenobarbital.
Testosterone propionate The metabolism of Aprocitentan can be increased when combined with Testosterone propionate.
Mitapivat The metabolism of Aprocitentan can be increased when combined with Mitapivat.
Adenine The metabolism of Aprocitentan can be decreased when combined with Adenine.
Indinavir The metabolism of Aprocitentan can be decreased when combined with Indinavir.
Valproic acid The metabolism of Aprocitentan can be decreased when combined with Valproic acid.
Amitriptyline The metabolism of Aprocitentan can be decreased when combined with Amitriptyline.
Indomethacin The therapeutic efficacy of Aprocitentan can be decreased when used in combination with Indomethacin.
Sorafenib The metabolism of Aprocitentan can be decreased when combined with Sorafenib.
Erlotinib The metabolism of Aprocitentan can be decreased when combined with Erlotinib.
Flurbiprofen The therapeutic efficacy of Aprocitentan can be decreased when used in combination with Flurbiprofen.
Propofol The metabolism of Aprocitentan can be decreased when combined with Propofol.
Ketoconazole The metabolism of Aprocitentan can be decreased when combined with Ketoconazole.
Probenecid The metabolism of Aprocitentan can be decreased when combined with Probenecid.
Atazanavir The metabolism of Aprocitentan can be decreased when combined with Atazanavir.
Gemfibrozil The metabolism of Aprocitentan can be decreased when combined with Gemfibrozil.
Flunitrazepam The metabolism of Aprocitentan can be decreased when combined with Flunitrazepam.
Deferasirox The metabolism of Aprocitentan can be decreased when combined with Deferasirox.
Nilotinib The metabolism of Aprocitentan can be decreased when combined with Nilotinib.
Eltrombopag The metabolism of Aprocitentan can be decreased when combined with Eltrombopag.
Pazopanib The metabolism of Aprocitentan can be decreased when combined with Pazopanib.
Regorafenib The metabolism of Aprocitentan can be decreased when combined with Regorafenib.
Dabrafenib The metabolism of Aprocitentan can be decreased when combined with Dabrafenib.
Dasabuvir The metabolism of Aprocitentan can be decreased when combined with Dasabuvir.
Sodium aurothiomalate The metabolism of Aprocitentan can be decreased when combined with Sodium aurothiomalate.
Ombitasvir The metabolism of Aprocitentan can be decreased when combined with Ombitasvir.
Paritaprevir The metabolism of Aprocitentan can be decreased when combined with Paritaprevir.
Silibinin The metabolism of Aprocitentan can be decreased when combined with Silibinin.
Encorafenib The metabolism of Aprocitentan can be decreased when combined with Encorafenib.
Dacomitinib The metabolism of Aprocitentan can be decreased when combined with Dacomitinib.
Fostamatinib The metabolism of Aprocitentan can be decreased when combined with Fostamatinib.
Asciminib The metabolism of Aprocitentan can be decreased when combined with Asciminib.
Quizartinib The metabolism of Aprocitentan can be decreased when combined with Quizartinib.
Pexidartinib The metabolism of Aprocitentan can be decreased when combined with Pexidartinib.
Enasidenib The metabolism of Aprocitentan can be decreased when combined with Enasidenib.
Pibrentasvir The metabolism of Aprocitentan can be decreased when combined with Pibrentasvir.
Glecaprevir The metabolism of Aprocitentan can be decreased when combined with Glecaprevir.
Repotrectinib The metabolism of Aprocitentan can be decreased when combined with Repotrectinib.
Mefenamic acid The therapeutic efficacy of Aprocitentan can be decreased when used in combination with Mefenamic acid.
Dovitinib The metabolism of Aprocitentan can be decreased when combined with Dovitinib.
Chenodeoxycholic acid The metabolism of Aprocitentan can be decreased when combined with Chenodeoxycholic acid.
Cannabidiol Cannabidiol may decrease the antihypertensive activities of Aprocitentan.
Cannabinol The metabolism of Aprocitentan can be increased when combined with Cannabinol.
Sparsentan The risk or severity of adverse effects can be increased when Aprocitentan is combined with Sparsentan.
Alfuzosin Alfuzosin may increase the hypotensive activities of Aprocitentan.
Amifostine Aprocitentan may increase the hypotensive activities of Amifostine.
Diazoxide Diazoxide may increase the hypotensive activities of Aprocitentan.
Methylphenidate Methylphenidate may decrease the antihypertensive activities of Aprocitentan.
Dexmethylphenidate Dexmethylphenidate may decrease the antihypertensive activities of Aprocitentan.
Obinutuzumab Aprocitentan may increase the hypotensive activities of Obinutuzumab.
Pentoxifylline Pentoxifylline may increase the hypotensive activities of Aprocitentan.
Rituximab Aprocitentan may increase the hypotensive activities of Rituximab.
Desmopressin Desmopressin may decrease the antihypertensive activities of Aprocitentan.
Cyclosporine Cyclosporine may decrease the antihypertensive activities of Aprocitentan.
Icosapent The therapeutic efficacy of Aprocitentan can be decreased when used in combination with Icosapent.
Amphetamine Amphetamine may decrease the antihypertensive activities of Aprocitentan.
Phentermine Phentermine may decrease the antihypertensive activities of Aprocitentan.
Midodrine Midodrine may decrease the antihypertensive activities of Aprocitentan.
Eletriptan Eletriptan may decrease the antihypertensive activities of Aprocitentan.
Bethanidine Bethanidine may decrease the antihypertensive activities of Aprocitentan.
Isoetharine Isoetharine may decrease the antihypertensive activities of Aprocitentan.
Mesalazine Mesalazine may decrease the antihypertensive activities of Aprocitentan.
Ziprasidone Ziprasidone may increase the antihypertensive activities of Aprocitentan.
Methysergide Methysergide may decrease the antihypertensive activities of Aprocitentan.
Cabergoline Cabergoline may decrease the antihypertensive activities of Aprocitentan.
Atomoxetine Atomoxetine may decrease the antihypertensive activities of Aprocitentan.
Etomidate Etomidate may decrease the antihypertensive activities of Aprocitentan.
Zolmitriptan Zolmitriptan may decrease the antihypertensive activities of Aprocitentan.
Dihydroergotamine Dihydroergotamine may decrease the antihypertensive activities of Aprocitentan.
Protriptyline Protriptyline may decrease the antihypertensive activities of Aprocitentan.
Methylergometrine Methylergometrine may decrease the antihypertensive activities of Aprocitentan.
Clozapine Clozapine may decrease the antihypertensive activities of Aprocitentan.
Norepinephrine Norepinephrine may decrease the antihypertensive activities of Aprocitentan.
Mirtazapine Mirtazapine may decrease the antihypertensive activities of Aprocitentan.
Phenylephrine Phenylephrine may decrease the antihypertensive activities of Aprocitentan.
Phenylpropanolamine Phenylpropanolamine may decrease the antihypertensive activities of Aprocitentan.
Promazine Promazine may decrease the antihypertensive activities of Aprocitentan.
Droperidol Droperidol may decrease the antihypertensive activities of Aprocitentan.
Imipramine Imipramine may decrease the antihypertensive activities of Aprocitentan.
Nabumetone The therapeutic efficacy of Aprocitentan can be decreased when used in combination with Nabumetone.
Ketorolac The therapeutic efficacy of Aprocitentan can be decreased when used in combination with Ketorolac.
Tenoxicam The therapeutic efficacy of Aprocitentan can be decreased when used in combination with Tenoxicam.
Chlorpromazine Chlorpromazine may decrease the antihypertensive activities of Aprocitentan.
Celecoxib The therapeutic efficacy of Aprocitentan can be decreased when used in combination with Celecoxib.
Buspirone Buspirone may decrease the antihypertensive activities of Aprocitentan.
Tolmetin The therapeutic efficacy of Aprocitentan can be decreased when used in combination with Tolmetin.
Rofecoxib The therapeutic efficacy of Aprocitentan can be decreased when used in combination with Rofecoxib.
Nortriptyline Nortriptyline may decrease the antihypertensive activities of Aprocitentan.

Target Protein

Endothelin-1 receptor EDNRA
Endothelin receptor type B EDNRB

Referensi & Sumber

Synthesis reference: Martin Bolli, Christoph Boss, Alexander Treiber. " 4-pyrimidinesulfamide derivative ", US Patent US8324232B2.
Artikel (PubMed)
  • PMID: 37566184
    Heidari Nejad S, Azzam O, Schlaich MP: Dual Endothelin Antagonism with Aprocitentan as a Novel Therapeutic Approach for Resistant Hypertension. Curr Hypertens Rep. 2023 Oct;25(10):343-352. doi: 10.1007/s11906-023-01259-z. Epub 2023 Aug 11.
  • PMID: 35245103
    Clozel M: Aprocitentan and the endothelin system in resistant hypertension. Can J Physiol Pharmacol. 2022 Jul 1;100(7):573-583. doi: 10.1139/cjpp-2022-0010. Epub 2022 Apr 3.
  • PMID: 36352054
    Fontes MSC, Dingemanse J, Halabi A, Tomaszewska-Kiecana M, Sidharta PN: Single-dose pharmacokinetics, safety, and tolerability of the dual endothelin receptor antagonist aprocitentan in subjects with moderate hepatic impairment. Sci Rep. 2022 Nov 9;12(1):19067. doi: 10.1038/s41598-022-22470-z.
  • PMID: 33563190
    Sidharta PN, Fischer H, Dingemanse J: Absorption, Distribution, Metabolism, and Excretion of Aprocitentan, a Dual Endothelin Receptor Antagonist, in Humans. Curr Drug Metab. 2021;22(5):399-410. doi: 10.2174/1389200222666210204202815.

Contoh Produk & Brand

Produk: 2 • International brands: 0
Produk
  • Tryvio
    Tablet, film coated • 12.5 mg/1 • Oral • US • Approved
  • Tryvio
    Tablet, film coated • 12.5 mg/1 • Oral • US • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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