Peringatan Keamanan

As clinical experience with ubrogepant is limited, detailed toxicity information is not readily available. Prescribing information for ubrogepant recommends a monitoring period of at least 24 hours following overdose based on its 5 to 7 hour half-life.^L10926

Ubrogepant

DB15328

small molecule approved investigational

Deskripsi

Ubrogepant is indicated for the acute treatment of migraine headaches with or without aura in adults.^L10926 It was approved by the FDA on December 23, 2019, and is the first oral calcitonin gene-related peptide (CGRP) receptor antagonist approved for the acute treatment of migraine.^L10959 Several oral small molecule CGRP receptor antagonists, belonging to a class of medications referred to as "gepants", have been investigated for migraines, but only ubrogepant and rimegepant remain in clinical development.A189207,A189213 Previous agents within this class were efficacious but limited by liver toxicity - this led to the development of ubrogepant, which was designed to be a hepatoxicity-free alternative to its predecessors.^A189195 Several parenteral monoclonal antibodies acting against the CGRP pathway (e.g. erenumab, fremanezumab, galcanezumab) have also been approved in recent years.^A189207 Ubrogepant was approved by Health Canada on November 10, 2022.^L43987

Compared to the current standard of therapy for migraine treatment, namely triptans such as sumatriptan and almotriptan, CGRP antagonists present several advantages.^A189195 They appear to be better tolerated, do not contribute to medication overuse headaches, and carry no apparent cardiovascular risk, making them suitable for use in patients with cardiovascular disease.^A189195 The development of oral gepants, including ubrogepant, may therefore constitute a significant advance in migraine headache treatment and may become the new standard of therapy in the treatment of this debilitating condition.

Struktur Molekul 2D

Berat 549.554

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) Ubrogepant has an elimination half-life of 5-7 hours.[L10926]

Volume Distribusi The apparent central volume of distribution following oral administration is approximately 350 L.[L10926]

Klirens (Clearance) The apparent oral clearance of ubrogepant is approximately 87 L/h.[L10926]

Absorpsi

Following oral administration, T_max occurs between 0.7 and 1.5 h.A189213,L10926 When administered with a high-fat meal, T_max is delayed by approximately 2 hours and C_max was reduced by 22% with no significant changes to the AUC.^L10926 Ubrogepant exhibits dose-proportional pharmacokinetics throughout the entirety of its recommended dosing range.^L10926

Metabolisme

Ubrogepant is eliminated primarily via metabolism, the majority of which is mediated by CYP3A4.^L10926 Two circulating glucuronide conjugates, along with unchanged parent drug, were found to be the most abundant circulating components in human plasma. The glucuronide metabolites reportedly carry 6000-fold less activity at CGRP receptors and are therefore considered to be pharmacologically inert.^L10926

Rute Eliminasi

The main route of elimination is fecal/biliary, while renal excretion is comparatively minor - following administration of a single oral dose to healthy subjects, approximately 42% of the dose was recovered unchanged in the feces and 6% was recovered unchanged in the urine.^L10926

Interaksi Makanan

2 Data

1. Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of ubrogepant.
2. Take with or without food. Co-administration with food slightly alters pharmacokinetics, but not to a clinically significant extent.

Interaksi Obat

415 Data

Ranolazine	The serum concentration of Ubrogepant can be increased when it is combined with Ranolazine.
Vemurafenib	The serum concentration of Ubrogepant can be increased when it is combined with Vemurafenib.
Pitolisant	The serum concentration of Ubrogepant can be decreased when it is combined with Pitolisant.
Cholesterol	Cholesterol may increase the excretion rate of Ubrogepant which could result in a lower serum level and potentially a reduction in efficacy.
Venlafaxine	Venlafaxine may increase the excretion rate of Ubrogepant which could result in a lower serum level and potentially a reduction in efficacy.
Metreleptin	The metabolism of Ubrogepant can be increased when combined with Metreleptin.
Digitoxin	The serum concentration of Digitoxin can be increased when it is combined with Ubrogepant.
Digoxin	The serum concentration of Digoxin can be increased when it is combined with Ubrogepant.
Vincristine	The serum concentration of Vincristine can be increased when it is combined with Ubrogepant.
Sirolimus	The serum concentration of Sirolimus can be increased when it is combined with Ubrogepant.
Topotecan	The serum concentration of Topotecan can be increased when it is combined with Ubrogepant.
Bosutinib	The serum concentration of Ubrogepant can be increased when it is combined with Bosutinib.
Bendamustine	The serum concentration of Bendamustine can be increased when it is combined with Ubrogepant.
Brentuximab vedotin	The serum concentration of Brentuximab vedotin can be increased when it is combined with Ubrogepant.
Binimetinib	The serum concentration of Binimetinib can be increased when it is combined with Ubrogepant.
Bortezomib	The serum concentration of Bortezomib can be increased when it is combined with Ubrogepant.
Cabergoline	The serum concentration of Cabergoline can be increased when it is combined with Ubrogepant.
Gemcitabine	The serum concentration of Gemcitabine can be increased when it is combined with Ubrogepant.
Imipramine	The serum concentration of Imipramine can be increased when it is combined with Ubrogepant.
Trimipramine	The serum concentration of Trimipramine can be increased when it is combined with Ubrogepant.
Axitinib	The serum concentration of Axitinib can be increased when it is combined with Ubrogepant.
Nortriptyline	The serum concentration of Nortriptyline can be increased when it is combined with Ubrogepant.
Morphine	The serum concentration of Ubrogepant can be increased when it is combined with Morphine.
Clobazam	The serum concentration of Ubrogepant can be increased when it is combined with Clobazam.
Mannitol	The serum concentration of Ubrogepant can be increased when it is combined with Mannitol.
Clomifene	The serum concentration of Ubrogepant can be increased when it is combined with Clomifene.
Fexofenadine	The serum concentration of Ubrogepant can be increased when it is combined with Fexofenadine.
Tegaserod	The serum concentration of Ubrogepant can be increased when it is combined with Tegaserod.
Sitagliptin	The serum concentration of Ubrogepant can be increased when it is combined with Sitagliptin.
Colchicine	The serum concentration of Ubrogepant can be increased when it is combined with Colchicine.
Belinostat	The serum concentration of Ubrogepant can be increased when it is combined with Belinostat.
Indacaterol	The serum concentration of Ubrogepant can be increased when it is combined with Indacaterol.
Cobimetinib	The serum concentration of Cobimetinib can be increased when it is combined with Ubrogepant.
Trastuzumab emtansine	The serum concentration of Trastuzumab emtansine can be increased when it is combined with Ubrogepant.
Romidepsin	The serum concentration of Romidepsin can be increased when it is combined with Ubrogepant.
Silodosin	The serum concentration of Ubrogepant can be increased when it is combined with Silodosin.
Rivaroxaban	The serum concentration of Ubrogepant can be increased when it is combined with Rivaroxaban.
Ambrisentan	The serum concentration of Ubrogepant can be increased when it is combined with Ambrisentan.
Panobinostat	The serum concentration of Panobinostat can be increased when it is combined with Ubrogepant.
Apixaban	The serum concentration of Ubrogepant can be increased when it is combined with Apixaban.
Odanacatib	The serum concentration of Ubrogepant can be increased when it is combined with Odanacatib.
Pomalidomide	The serum concentration of Pomalidomide can be increased when it is combined with Ubrogepant.
Dolutegravir	The serum concentration of Ubrogepant can be increased when it is combined with Dolutegravir.
Sofosbuvir	The serum concentration of Ubrogepant can be increased when it is combined with Sofosbuvir.
Edoxaban	The serum concentration of Ubrogepant can be increased when it is combined with Edoxaban.
Umeclidinium	The serum concentration of Ubrogepant can be increased when it is combined with Umeclidinium.
Nintedanib	The serum concentration of Ubrogepant can be increased when it is combined with Nintedanib.
Technetium Tc-99m sestamibi	The serum concentration of Ubrogepant can be increased when it is combined with Technetium Tc-99m sestamibi.
Ombitasvir	The serum concentration of Ubrogepant can be increased when it is combined with Ombitasvir.
Selexipag	The serum concentration of Ubrogepant can be increased when it is combined with Selexipag.
Elbasvir	The serum concentration of Ubrogepant can be increased when it is combined with Elbasvir.
Grazoprevir	The serum concentration of Ubrogepant can be increased when it is combined with Grazoprevir.
Vinflunine	The serum concentration of Vinflunine can be increased when it is combined with Ubrogepant.
Talazoparib	The serum concentration of Talazoparib can be increased when it is combined with Ubrogepant.
Talinolol	The serum concentration of Ubrogepant can be increased when it is combined with Talinolol.
Revefenacin	The serum concentration of Ubrogepant can be increased when it is combined with Revefenacin.
Duvelisib	The serum concentration of Ubrogepant can be increased when it is combined with Duvelisib.
Betrixaban	The serum concentration of Ubrogepant can be increased when it is combined with Betrixaban.
Omadacycline	The serum concentration of Ubrogepant can be increased when it is combined with Omadacycline.
Grapiprant	The serum concentration of Ubrogepant can be increased when it is combined with Grapiprant.
Enfortumab vedotin	The serum concentration of Ubrogepant can be increased when it is combined with Enfortumab vedotin.
Tenofovir	The serum concentration of Ubrogepant can be increased when it is combined with Tenofovir.
Tazemetostat	The serum concentration of Ubrogepant can be increased when it is combined with Tazemetostat.
Lemborexant	The serum concentration of Ubrogepant can be increased when it is combined with Lemborexant.
Lefamulin	The serum concentration of Ubrogepant can be increased when it is combined with Lefamulin.
Vinblastine	The serum concentration of Vinblastine can be increased when it is combined with Ubrogepant.
Bisoprolol	The serum concentration of Ubrogepant can be increased when it is combined with Bisoprolol.
Etoposide	The serum concentration of Etoposide can be increased when it is combined with Ubrogepant.
Dactinomycin	The serum concentration of Dactinomycin can be increased when it is combined with Ubrogepant.
Tolvaptan	The serum concentration of Tolvaptan can be increased when it is combined with Ubrogepant.
Tezacaftor	The serum concentration of Ubrogepant can be increased when it is combined with Tezacaftor.
Tenofovir disoproxil	The serum concentration of Ubrogepant can be increased when it is combined with Tenofovir disoproxil.
Rimegepant	The serum concentration of Ubrogepant can be increased when it is combined with Rimegepant.
Lusutrombopag	The serum concentration of Ubrogepant can be increased when it is combined with Lusutrombopag.
Selumetinib	The serum concentration of Ubrogepant can be increased when it is combined with Selumetinib.
Dabigatran etexilate	The serum concentration of Ubrogepant can be increased when it is combined with Dabigatran etexilate.
Idelalisib	The serum concentration of Ubrogepant can be increased when it is combined with Idelalisib.
Prednisolone phosphate	The serum concentration of Ubrogepant can be increased when it is combined with Prednisolone phosphate.
Belantamab mafodotin	The serum concentration of Belantamab mafodotin can be increased when it is combined with Ubrogepant.
Relugolix	The serum concentration of Ubrogepant can be increased when it is combined with Relugolix.
Lenvatinib	The serum concentration of Ubrogepant can be increased when it is combined with Lenvatinib.
Trilaciclib	The serum concentration of Trilaciclib can be increased when it is combined with Ubrogepant.
Daptomycin	The serum concentration of Ubrogepant can be increased when it is combined with Daptomycin.
Loncastuximab tesirine	The serum concentration of Loncastuximab tesirine can be increased when it is combined with Ubrogepant.
Cenobamate	The serum concentration of Ubrogepant can be decreased when it is combined with Cenobamate.
Cyclosporine	The serum concentration of Ubrogepant can be increased when it is combined with Cyclosporine.
Fluvoxamine	The serum concentration of Ubrogepant can be increased when it is combined with Fluvoxamine.
Fluconazole	The serum concentration of Ubrogepant can be increased when it is combined with Fluconazole.
Erythromycin	The serum concentration of Ubrogepant can be increased when it is combined with Erythromycin.
Ziprasidone	The serum concentration of Ubrogepant can be increased when it is combined with Ziprasidone.
Isradipine	The serum concentration of Ubrogepant can be increased when it is combined with Isradipine.
Diltiazem	The serum concentration of Ubrogepant can be increased when it is combined with Diltiazem.
Clozapine	The serum concentration of Ubrogepant can be increased when it is combined with Clozapine.
Haloperidol	The serum concentration of Ubrogepant can be increased when it is combined with Haloperidol.
Ciprofloxacin	The serum concentration of Ubrogepant can be increased when it is combined with Ciprofloxacin.
Nicardipine	The serum concentration of Ubrogepant can be increased when it is combined with Nicardipine.
Verapamil	The serum concentration of Ubrogepant can be increased when it is combined with Verapamil.
Aprepitant	The serum concentration of Ubrogepant can be increased when it is combined with Aprepitant.
Isoniazid	The serum concentration of Ubrogepant can be increased when it is combined with Isoniazid.
Tioconazole	The serum concentration of Ubrogepant can be increased when it is combined with Tioconazole.

Target Protein

Calcitonin gene-related peptide type 1 receptor CALCRL

Referensi & Sumber

Synthesis reference: Leonardo R. Allain, et. al., "Formulations for CGRP receptor antagonists." Australian Patent AU2014318741B2, published December 06, 2018.

Artikel (PubMed)

PMID: 31291016
Moreno-Ajona D, Chan C, Villar-Martinez MD, Goadsby PJ: Targeting CGRP and 5-HT1F Receptors for the Acute Therapy of Migraine: A Literature Review. Headache. 2019 Jul;59 Suppl 2:3-19. doi: 10.1111/head.13582.
PMID: 31674221
Rubio-Beltran E, Chan KY, Danser AJ, MaassenVanDenBrink A, Edvinsson L: Characterisation of the calcitonin gene-related peptide receptor antagonists ubrogepant and atogepant in human isolated coronary, cerebral and middle meningeal arteries. Cephalalgia. 2019 Nov 1:333102419884943. doi: 10.1177/0333102419884943.
PMID: 31081399
Negro A, Martelletti P: Gepants for the treatment of migraine. Expert Opin Investig Drugs. 2019 Jun;28(6):555-567. doi: 10.1080/13543784.2019.1618830. Epub 2019 May 17.
PMID: 30475090
Martelletti P, Giamberardino MA: Advances in orally administered pharmacotherapy for the treatment of migraine. Expert Opin Pharmacother. 2019 Feb;20(2):209-218. doi: 10.1080/14656566.2018.1549223. Epub 2018 Nov 26.

Link

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Produk: 4 • International brands: 0

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Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.