Peringatan Keamanan

Toxicity information regarding omidenepag isopropyl is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as ocular inflammation.^L43503 Symptomatic and supportive measures are recommended. Lifetime studies evaluating the carcinogenic effects of omidenepag isopropyl or omidenepag have not been performed. In rats given omidenepag isopropyl subcutaneously for 26 weeks, nephroblastoma and a spermatic cord tumor were developed at 0.003 mg/kg/day (33 times the recommended human ophthalmic dose). At 0.03 mg/kg/day (319 times the recommended human ophthalmic dose), rats given omidenepag isopropyl developed mammary adenocarcinoma and pituitary pars distalis adenomas. Based on the results of the in vitro mouse lymphoma forward mutation assay, omidenepag isopropyl (no metabolic activation) was mutagenic and clastogenic. Its active metabolite, omidenepag, was not mutagenic in the in vivo mouse micronucleus and bacterial reverse mutation tests.^L43503

Omidenepag isopropyl

DB15071

small molecule approved investigational

Deskripsi

Omidenepag isopropyl is a topical ocular hypotensive agent used to reduce intraocular pressure (IOP) in patients with glaucoma and ocular hypertension.^L43503 Omidenepag isopropyl is quickly metabolized to its active metabolite, omidenepag, a molecule with high selectivity and agonistic activity towards the prostaglandin E2 (EP2) receptor.A253263,A253268 Prostanoid FP receptor agonists (FP agonists), such as latanoprost, are part of the first-line therapy for ocular hypertension and primary open-angle glaucoma; however, not all patients achieve adequate IOP reduction with FP agonists and require changes in treatment. The use of an EP2 receptor agonist such as omidenepag represents an alternative in these scenarios. Omidenepag IOP-lowering effect is comparable to the one observed with latanoprost.^A253253 In 2018, omidenepag isopropyl was approved in Japan for the treatment of glaucoma and ocular hypertension.^A253268 In September 2022, the FDA approved the use of omidenepag isopropyl.^L43503

Struktur Molekul 2D

Berat 520.61

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 omidenepag isopropyl is not available. The mean terminal half-life of its active metabolite, omidenepag, is approximately 30 minutes.[L43508]

Volume Distribusi Not available.

Klirens (Clearance) Not available.

Absorpsi

The ophthalmic solution of omidenepag isopropyl is absorbed through the cornea, where it is hydrolyzed into its active metabolite, omidenepag. After the administration of one drop of omidenepag isopropyl 0.0025% eye drops to both eyes for 7 days, plasma concentration in humans reached C_max at 10-15 minutes. There was no evidence of omidenepag isopropyl systemic accumulation, given that systemic exposure was similar between days 1 and 7.^L43503 A study comparing the pharmacokinetic parameters of omidenepag in Japanese and Caucasian healthy subjects did not find significant differences. Japanese and Caucasian healthy subjects had a corresponding C_max of 41.5 ± 20.1 and 27.2 ± 10.2 pg/mL, and a corresponding AUC_{0-8 h} of 26.1 ± 5.7 and 15.3 ± 4.7 h·pg/mL (mean ± standard deviation).^A253243

Metabolisme

Omidenepag isopropyl is rapidly metabolized after topical ocular administration by carboxylesterase-1 to its pharmacologically active form, omidenepag. In the liver, omidenepag is further metabolized through oxidation, N-dealkylation, glucuronidation, sulfate conjugation or taurine conjugation.^L43503 CYP3A4 plas an important role in the liver metabolism of omidenepag.A253243,L43508

Rute Eliminasi

In rats given 0.03% omidenepag isopropyl in both eyes as a single dose (5 mcL/eye, 3 mcg/animal), 89% of the administered dose was excreted 168 hours after ocular instillation. Omidenepag was eliminated in feces (83%) and urine (4%).^L43503

Interaksi Obat

0 Data

Tidak ada data.

Target Protein

Prostaglandin E2 receptor EP2 subtype PTGER2

Prostaglandin E2 receptor EP1 subtype PTGER1

Referensi & Sumber

Synthesis reference: Pharmaceutical composition for treating or preventing glaucoma (WO 2010/113957 A1). World Intellectual Property Organization. https://patents.google.com/patent/WO2010113957A1/en

Artikel (PubMed)

PMID: 31674861
Aihara M, Lu F, Kawata H, Tanaka Y, Yamamura K, Odani-Kawabata N, Shams NK: Pharmacokinetics, Safety, and Intraocular Pressure-Lowering Profile of Omidenepag Isopropyl, a Selective, Nonprostaglandin, Prostanoid EP2 Receptor Agonist, in Healthy Japanese and Caucasian Volunteers (Phase I Study). J Ocul Pharmacol Ther. 2019 Dec;35(10):542-550. doi: 10.1089/jop.2019.0044. Epub 2019 Nov 1.
PMID: 32533949
Aihara M, Lu F, Kawata H, Iwata A, Odani-Kawabata N, Shams NK: Omidenepag Isopropyl Versus Latanoprost in Primary Open-Angle Glaucoma and Ocular Hypertension: The Phase 3 AYAME Study. Am J Ophthalmol. 2020 Dec;220:53-63. doi: 10.1016/j.ajo.2020.06.003. Epub 2020 Jun 10.
PMID: 29989843
Fuwa M, Toris CB, Fan S, Taniguchi T, Ichikawa M, Odani-Kawabata N, Iwamura R, Yoneda K, Matsugi T, Shams NK, Zhang JZ: Effects of a Novel Selective EP2 Receptor Agonist, Omidenepag Isopropyl, on Aqueous Humor Dynamics in Laser-Induced Ocular Hypertensive Monkeys. J Ocul Pharmacol Ther. 2018 Sep;34(7):531-537. doi: 10.1089/jop.2017.0146. Epub 2018 Jul 10.
PMID: 29332128
Kirihara T, Taniguchi T, Yamamura K, Iwamura R, Yoneda K, Odani-Kawabata N, Shimazaki A, Matsugi T, Shams N, Zhang JZ: Pharmacologic Characterization of Omidenepag Isopropyl, a Novel Selective EP2 Receptor Agonist, as an Ocular Hypotensive Agent. Invest Ophthalmol Vis Sci. 2018 Jan 1;59(1):145-153. doi: 10.1167/iovs.17-22745.
PMID: 30465134
Duggan S: Omidenepag Isopropyl Ophthalmic Solution 0.002%: First Global Approval. Drugs. 2018 Dec;78(18):1925-1929. doi: 10.1007/s40265-018-1016-1.

Link

Contoh Produk & Brand

Produk: 1 • International brands: 2

Produk

Omlonti

Solution / drops • 0.02 mg/1mL • Ophthalmic • US • Approved

International Brands

Eybelis — Santen Pharmaceutical
Omlonti — Santen Pharmaceutical

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.