Peringatan Keamanan

Based on animal studies, oteseconazole may cause embryo-fetal toxicity.^L41635 Additional toxicity information regarding oteseconazole is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects. In case of overdose, symptomatic and supportive measures are recommended.

In a murine carcinogenicity study, Sprague Dawley rats were administered 0.5, 1.5, or 5 mg/kg/day of oral oteseconazole. Due to high mortality, the highest dose was reduced to 3 mg/kg/day.^L41635 After 77 weeks, rats receiving 5 times the maximum recommended human dose had a higher incidence of hemorrhage in the adrenals, brain, coagulating gland, ears, epididymides, head, heart, lung, nose, pancreas, pharynx, prostate, seminal vesicles, spinal cord, testes, thymus, and bladder.^L41635 At 26 weeks, rats receiving 5 mg/kg/day of oteseconazole did not have a higher incidence of hemorrhage. These animal studies were performed using very high doses of oteseconazole (5 to 7 times the maximum recommended human dose), and their clinical relevance remains unclear.^L41635

Oteseconazole

DB13055

small molecule approved investigational

Deskripsi

Oteseconazole is an azole metalloenzyme inhibitor that targets fungal CYP51.^L41635 CYP51, also known as 14? demethylase, participates in the formation of ergosterol, a compound that plays a vital role in the integrity of cell membranes.L41635,A247020 By binding and inhibiting CYP51, oteseconazole is active against most microorganisms associated with recurrent vulvovaginal candidiasis (RVVC).^L41635 Oteseconazole has demonstrated activity against Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis, Candida lusitaniae and Candida dubliniensis.^L41635

Unlike previous-generation azole antifungals, oteseconazole has a high selectivity for CYP51 and little interaction with human cytochrome P450s.^A247035 This is possible thanks to the tetrazole moiety in oteseconazole that increases target selectivity.^A247035 In contrast with oteseconazole, other antifungals with imidazole or triazole moieties, such as ketoconazole or fluconazole, have a high number of drug-drug interactions due to their interaction with human CYPs.^A247050

The use of oteseconazole is contraindicated in females of reproductive potential due to its embryo-fetal toxicity risks.^L41635 This drug was approved by the FDA on April 26, 2022.^L41645

Struktur Molekul 2D

Berat 527.403

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 median terminal half-life of oteseconazole is approximately 138 days.[L41635]

Volume Distribusi On average, the volume of distribution of oteseconazole is 423 L.[L41635]

Klirens (Clearance) Clinical phase I studies performed in healthy adults found that the clearance of oteseconazole is not affected by age or sex, and that the relationship between weight and clearance is approximately linear. The clearance of oteseconazole in non-white participants was 48% higher than the one detected in white participants, although the reasons for this are unknown.[A247035]

Absorpsi

Between 20 mg and 320 mg, the AUC of oteseconazole increased relatively dose proportionally, and the C_max increased less than dose proportionally. On average, the AUC was 64.2 h·µg/mL, and the C_max was 2.8 µg/mL at the end of recurrent vulvovaginal candidiasis (RVVC) treatment.^L41635 The t_max of oteseconazole ranged from 5 to 10 hours.^L41635 Sex, race/ethnicity, and mild to moderate renal impairment do not have a significant effect on the pharmacokinetics of oteseconazole.^L41635 The bioavailability of oteseconazole is affected by high-fat, high-calorie meals. With a diet that had 800-1000 Calories and 50% fat, C_max and AUC_0-72h were 45% and 36% higher, respectively. No significant differences were detected with a low-fat, low-calorie meal.^L41635 Animal models have shown that the bioavailability of oteseconazole is high. In a murine model, bioavailability was 73%. In dogs, bioavailability was 40% after fasting, and 100% in a fed state.^A247035 Pre-clinical studies have shown that oteseconazole exposure in vaginal tissue is similar to plasma exposure.^L41635

Metabolisme

Oteseconazole does not undergo significant metabolism.^L41635

Rute Eliminasi

The majority of oteseconazole is excreted via feces and bile, and low levels of it can be found in urine.^A247035

Interaksi Makanan

1 Data

1. Take with food. Oteseconazole must be taken with food, and capsules must be swallowed whole and not chewed, crushed, dissolved, or opened. The intake of high-fat, high-calorie meals (800-1000 Calories; 50% fat) increases oteseconazole C_max and AUC_0-72h by 45% and 36%, respectively. No significant differences were detected when oteseconazole was administered with a low-fat, low-calorie meal.

Interaksi Obat

207 Data

Amphotericin B	The therapeutic efficacy of Amphotericin B can be decreased when used in combination with Oteseconazole.
Didanosine	Didanosine can cause a decrease in the absorption of Oteseconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Sildenafil	The serum concentration of Sildenafil can be increased when it is combined with Oteseconazole.
Sucralfate	Sucralfate can cause a decrease in the absorption of Oteseconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Atorvastatin	The risk or severity of myopathy can be increased when Oteseconazole is combined with Atorvastatin.
Isradipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Isradipine.
Diltiazem	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Diltiazem.
Trimethadione	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Trimethadione.
Amlodipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Amlodipine.
Nimodipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Nimodipine.
Nisoldipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Nisoldipine.
Lercanidipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Lercanidipine.
Cinnarizine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Cinnarizine.
Ethosuximide	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Ethosuximide.
Nicardipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Nicardipine.
Magnesium sulfate	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Magnesium sulfate.
Verapamil	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Verapamil.
Zonisamide	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Zonisamide.
Felodipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Felodipine.
Nitrendipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Nitrendipine.
Perhexiline	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Perhexiline.
Nifedipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Nifedipine.
Amiodarone	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Amiodarone.
Carvedilol	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Carvedilol.
Bepridil	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Bepridil.
Mibefradil	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Mibefradil.
Nimesulide	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Nimesulide.
Prenylamine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Prenylamine.
Cyclandelate	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Cyclandelate.
Flunarizine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Flunarizine.
Fluspirilene	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Fluspirilene.
Clevidipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Clevidipine.
Methsuximide	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Methsuximide.
Seletracetam	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Seletracetam.
Nylidrin	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Nylidrin.
Ziconotide	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Ziconotide.
Dotarizine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Dotarizine.
Xylometazoline	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Xylometazoline.
Nilvadipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Nilvadipine.
Tranilast	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Tranilast.
Fasudil	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Fasudil.
Agmatine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Agmatine.
Fendiline	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Fendiline.
Eperisone	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Eperisone.
Trimebutine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Trimebutine.
Pinaverium	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Pinaverium.
Barnidipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Barnidipine.
Aranidipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Aranidipine.
Azelnidipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Azelnidipine.
Benidipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Benidipine.
Cilnidipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Cilnidipine.
Darodipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Darodipine.
Efonidipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Efonidipine.
Lacidipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Lacidipine.
Levamlodipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Levamlodipine.
Manidipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Manidipine.
Niguldipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Niguldipine.
Niludipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Niludipine.
Carboxyamidotriazole	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Carboxyamidotriazole.
Naftopidil	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Naftopidil.
Tetrahydropalmatine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Tetrahydropalmatine.
Vinpocetine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Vinpocetine.
Gallopamil	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Gallopamil.
Bencyclane	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Bencyclane.
Otilonium	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Otilonium.
Terodiline	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Terodiline.
Lidoflazine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Lidoflazine.
Penfluridol	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Penfluridol.
Caroverine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Caroverine.
WIN 55212-2	The therapeutic efficacy of Oteseconazole can be increased when used in combination with WIN 55212-2.
Dexverapamil	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Dexverapamil.
Emopamil	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Emopamil.
Lomerizine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Lomerizine.
Tetrandrine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Tetrandrine.
Dexniguldipine	The therapeutic efficacy of Oteseconazole can be increased when used in combination with Dexniguldipine.
Folic acid	The serum concentration of Folic acid can be increased when it is combined with Oteseconazole.
Pravastatin	The serum concentration of Pravastatin can be increased when it is combined with Oteseconazole.
Conjugated estrogens	The serum concentration of Conjugated estrogens can be increased when it is combined with Oteseconazole.
Gefitinib	The serum concentration of Gefitinib can be increased when it is combined with Oteseconazole.
Allopurinol	The serum concentration of Allopurinol can be increased when it is combined with Oteseconazole.
Cerivastatin	The serum concentration of Cerivastatin can be increased when it is combined with Oteseconazole.
Teniposide	The serum concentration of Teniposide can be increased when it is combined with Oteseconazole.
Prazosin	The serum concentration of Prazosin can be increased when it is combined with Oteseconazole.
Raloxifene	The serum concentration of Raloxifene can be increased when it is combined with Oteseconazole.
Celecoxib	The serum concentration of Celecoxib can be increased when it is combined with Oteseconazole.
Zidovudine	The serum concentration of Zidovudine can be increased when it is combined with Oteseconazole.
Ritonavir	The serum concentration of Ritonavir can be increased when it is combined with Oteseconazole.
Oxaliplatin	The serum concentration of Oxaliplatin can be increased when it is combined with Oteseconazole.
Vincristine	The serum concentration of Vincristine can be increased when it is combined with Oteseconazole.
Fluorouracil	The serum concentration of Fluorouracil can be increased when it is combined with Oteseconazole.
Methotrexate	The serum concentration of Methotrexate can be increased when it is combined with Oteseconazole.
Ivermectin	The serum concentration of Ivermectin can be increased when it is combined with Oteseconazole.
Imatinib	The serum concentration of Imatinib can be increased when it is combined with Oteseconazole.
Testosterone	The serum concentration of Testosterone can be increased when it is combined with Oteseconazole.
Clofarabine	The serum concentration of Clofarabine can be increased when it is combined with Oteseconazole.
Sumatriptan	The serum concentration of Sumatriptan can be increased when it is combined with Oteseconazole.
Tamoxifen	The serum concentration of Tamoxifen can be increased when it is combined with Oteseconazole.
Mycophenolate mofetil	The serum concentration of Mycophenolate mofetil can be increased when it is combined with Oteseconazole.
Daunorubicin	The serum concentration of Daunorubicin can be increased when it is combined with Oteseconazole.
Nitrofurantoin	The serum concentration of Nitrofurantoin can be increased when it is combined with Oteseconazole.

Target Protein

Lanosterol 14-alpha demethylase ERG11

Referensi & Sumber

Synthesis reference: Hoekstra, WJ., et al. (2020). Antifungal compound process (U.S. Patent No. US 10,745,378 B2). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/f4/62/19/5ba525b1caad0e/US10745378.pdf

Artikel (PubMed)

PMID: 31068906
Zhang J, Li L, Lv Q, Yan L, Wang Y, Jiang Y: The Fungal CYP51s: Their Functions, Structures, Related Drug Resistance, and Inhibitors. Front Microbiol. 2019 Apr 24;10:691. doi: 10.3389/fmicb.2019.00691. eCollection 2019.
PMID: 32818963
Brand SR, Sobel JD, Nyirjesy P, Ghannoum MA, Schotzinger RJ, Degenhardt TP: A Randomized Phase 2 Study of VT-1161 for the Treatment of Acute Vulvovaginal Candidiasis. Clin Infect Dis. 2021 Oct 5;73(7):e1518-e1524. doi: 10.1093/cid/ciaa1204.
PMID: 34783586
Sobel JD, Nyirjesy P: Oteseconazole: an advance in treatment of recurrent vulvovaginal candidiasis. Future Microbiol. 2021 Dec;16:1453-1461. doi: 10.2217/fmb-2021-0173. Epub 2021 Nov 16.
PMID: 27820668
Chang YL, Yu SJ, Heitman J, Wellington M, Chen YL: New facets of antifungal therapy. Virulence. 2017 Feb 17;8(2):222-236. doi: 10.1080/21505594.2016.1257457. Epub 2016 Nov 7.

Link

Contoh Produk & Brand

Produk: 1 • International brands: 1

Produk

Vivjoa

Capsule • 150 mg/1 • Oral • US • Approved

International Brands

Vivjoa — Mycovia Pharmaceuticals, Inc.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.