Peringatan Keamanan

Specific data regarding vamorolone overdosage are not readily available. Prescribing information recommends supportive and symptomatic treatment in the event of suspected vamorolone overdose, with consideration given to gastric lavage or emesis if clinically appropriate.^L48671

Vamorolone

DB15114

small molecule approved investigational

Deskripsi

Vamorolone is a novel and fully synthetic glucocorticoid developed by Santhera Pharmaceuticals. It is used to manage inflammation and immune dysregulation in patients with Duchenne muscular dystrophy (DMD), a neuromuscular disorder characterized by the insidious regression of neuromuscular function and the most common form of muscular dystrophy in the United States.^L48676 Corticosteroid therapy is the current standard of care for DMD despite relatively high rates of adverse effects.^L48676 Vamorolone is positioned as having a more tolerable adverse effect profile than other corticosteroids owing to its unique receptor binding profile,^A261976 thus providing an additional treatment option in patients for whom corticosteroid adverse effects are intolerable or otherwise unacceptable.^L48676

Vamorolone was approved by the FDA in October 2023 for the management of DMD in patients ?2 years of age.L48671,L48676 In December 2023, it was approved in the EU for the treatment of patients ?4 years of age.^L49505

Struktur Molekul 2D

Berat 356.462

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 terminal elimination half-life of vamorolone is approximately 2 hours. [L48671]

Volume Distribusi Based on population pharmacokinetic analysis, the apparent volume of distribution of vamorolone when administered with a meal to a 20 kg patient with DMD is 162 L.[L48671]

Klirens (Clearance) Based on population pharmacokinetic analysis, the clearance of vamorolone when administered with a meal to a 20 kg patient with DMD is 58 L/h.[L48671]

Absorpsi

Following oral administration with food, the median T_max of vamorolone is approximately 2 hours.^L48671 The co-administration of vamorolone with a high-fat, high-calorie meal reduced C_max by 18%, increased AUC by 13%, and delayed T_max by one hour. The co-administration of vamorolone with a low-fat, low-calorie meal reduced C_max by 4%, increased AUC by 14%, and delayed T_max by one hour.^L48671

Metabolisme

Vamorolone is subject to multiple metabolic pathways, including glucuronidation, hydroxylation, and reduction.^L48671 Its metabolism is mediated through CYP3A4, CYP3A5, CYP2C8, UGT1A3, UGT2B7, and UGT2B17.^L48671 Glucuronides - formed via direct glucuronidation and hydrogenation with subsequent glucuronidation - are the main metabolites in the plasma and urine.^L48671

Rute Eliminasi

Approximately 30% of a given vamorolone dose is excreted in the feces (15.4% as unchanged parent drug) and 48% is excreted in the urine (<1% as unchanged parent drug).^L48671

Interaksi Makanan

1 Data

1. Take with food. Prescribing information for vamorolone states that it should preferably be administered with food.

Interaksi Obat

785 Data

Nelfinavir	The serum concentration of Vamorolone can be increased when it is combined with Nelfinavir.
Indinavir	The serum concentration of Vamorolone can be increased when it is combined with Indinavir.
Terfenadine	The serum concentration of Vamorolone can be increased when it is combined with Terfenadine.
Ritonavir	The serum concentration of Vamorolone can be increased when it is combined with Ritonavir.
Voriconazole	The serum concentration of Vamorolone can be increased when it is combined with Voriconazole.
Efavirenz	The serum concentration of Vamorolone can be increased when it is combined with Efavirenz.
Ergotamine	The serum concentration of Vamorolone can be increased when it is combined with Ergotamine.
Amprenavir	The serum concentration of Vamorolone can be increased when it is combined with Amprenavir.
Delavirdine	The serum concentration of Vamorolone can be increased when it is combined with Delavirdine.
Methimazole	The serum concentration of Vamorolone can be increased when it is combined with Methimazole.
Conivaptan	The serum concentration of Vamorolone can be increased when it is combined with Conivaptan.
Tipranavir	The serum concentration of Vamorolone can be increased when it is combined with Tipranavir.
Telithromycin	The serum concentration of Vamorolone can be increased when it is combined with Telithromycin.
Ketoconazole	The serum concentration of Vamorolone can be increased when it is combined with Ketoconazole.
Atazanavir	The serum concentration of Vamorolone can be increased when it is combined with Atazanavir.
Amiodarone	The serum concentration of Vamorolone can be increased when it is combined with Amiodarone.
Econazole	The serum concentration of Vamorolone can be increased when it is combined with Econazole.
Nefazodone	The serum concentration of Vamorolone can be increased when it is combined with Nefazodone.
Itraconazole	The serum concentration of Vamorolone can be increased when it is combined with Itraconazole.
Clarithromycin	The serum concentration of Vamorolone can be increased when it is combined with Clarithromycin.
Saquinavir	The serum concentration of Vamorolone can be increased when it is combined with Saquinavir.
Posaconazole	The serum concentration of Vamorolone can be increased when it is combined with Posaconazole.
Darunavir	The serum concentration of Vamorolone can be increased when it is combined with Darunavir.
Danazol	The serum concentration of Vamorolone can be increased when it is combined with Danazol.
Lopinavir	The serum concentration of Vamorolone can be increased when it is combined with Lopinavir.
Ditiocarb	The serum concentration of Vamorolone can be increased when it is combined with Ditiocarb.
Nilotinib	The serum concentration of Vamorolone can be increased when it is combined with Nilotinib.
Telaprevir	The serum concentration of Vamorolone can be increased when it is combined with Telaprevir.
Levoketoconazole	The serum concentration of Vamorolone can be increased when it is combined with Levoketoconazole.
Lonafarnib	The serum concentration of Vamorolone can be increased when it is combined with Lonafarnib.
Midostaurin	The serum concentration of Vamorolone can be increased when it is combined with Midostaurin.
Boceprevir	The serum concentration of Vamorolone can be increased when it is combined with Boceprevir.
Elvitegravir	The serum concentration of Vamorolone can be increased when it is combined with Elvitegravir.
Stiripentol	The serum concentration of Vamorolone can be increased when it is combined with Stiripentol.
Curcumin	The serum concentration of Vamorolone can be increased when it is combined with Curcumin.
Ribociclib	The serum concentration of Vamorolone can be increased when it is combined with Ribociclib.
Danoprevir	The serum concentration of Vamorolone can be increased when it is combined with Danoprevir.
Troleandomycin	The serum concentration of Vamorolone can be increased when it is combined with Troleandomycin.
Phenytoin	The serum concentration of Vamorolone can be decreased when it is combined with Phenytoin.
Pentobarbital	The metabolism of Vamorolone can be increased when combined with Pentobarbital.
Carbamazepine	The metabolism of Vamorolone can be increased when combined with Carbamazepine.
Mitotane	The serum concentration of Vamorolone can be decreased when it is combined with Mitotane.
Primidone	The metabolism of Vamorolone can be increased when combined with Primidone.
Rifampin	The metabolism of Vamorolone can be increased when combined with Rifampicin.
Phenobarbital	The metabolism of Vamorolone can be increased when combined with Phenobarbital.
Rifapentine	The metabolism of Vamorolone can be increased when combined with Rifapentine.
Dexamethasone	The metabolism of Vamorolone can be increased when combined with Dexamethasone.
Fosphenytoin	The serum concentration of Vamorolone can be decreased when it is combined with Fosphenytoin.
St. John's Wort	The metabolism of Vamorolone can be increased when combined with St. John's Wort.
Enzalutamide	The serum concentration of Vamorolone can be decreased when it is combined with Enzalutamide.
Lumacaftor	The metabolism of Vamorolone can be increased when combined with Lumacaftor.
Apalutamide	The serum concentration of Vamorolone can be decreased when it is combined with Apalutamide.
Cyclosporine	The risk or severity of adverse effects can be increased when Vamorolone is combined with Cyclosporine.
Fluvoxamine	The metabolism of Vamorolone can be decreased when combined with Fluvoxamine.
Fluconazole	The metabolism of Vamorolone can be decreased when combined with Fluconazole.
Erythromycin	The serum concentration of Vamorolone can be increased when it is combined with Erythromycin.
Ziprasidone	The metabolism of Vamorolone can be decreased when combined with Ziprasidone.
Isradipine	The metabolism of Vamorolone can be decreased when combined with Isradipine.
Diltiazem	The metabolism of Vamorolone can be decreased when combined with Diltiazem.
Clozapine	The metabolism of Vamorolone can be decreased when combined with Clozapine.
Haloperidol	The serum concentration of Haloperidol can be increased when it is combined with Vamorolone.
Ciprofloxacin	The risk or severity of tendinopathy can be increased when Vamorolone is combined with Ciprofloxacin.
Nicardipine	The metabolism of Vamorolone can be decreased when combined with Nicardipine.
Verapamil	The metabolism of Vamorolone can be decreased when combined with Verapamil.
Aprepitant	The metabolism of Vamorolone can be decreased when combined with Aprepitant.
Isoniazid	The serum concentration of Isoniazid can be decreased when it is combined with Vamorolone.
Primaquine	The metabolism of Vamorolone can be decreased when combined with Primaquine.
Miconazole	The metabolism of Vamorolone can be decreased when combined with Miconazole.
Fusidic acid	The metabolism of Vamorolone can be decreased when combined with Fusidic acid.
Zimelidine	The metabolism of Vamorolone can be decreased when combined with Zimelidine.
Dronedarone	The metabolism of Vamorolone can be decreased when combined with Dronedarone.
Milnacipran	The metabolism of Vamorolone can be decreased when combined with Milnacipran.
Simeprevir	The metabolism of Vamorolone can be decreased when combined with Simeprevir.
Isavuconazonium	The metabolism of Vamorolone can be decreased when combined with Isavuconazonium.
Desvenlafaxine	The metabolism of Vamorolone can be decreased when combined with Desvenlafaxine.
Nilvadipine	The metabolism of Vamorolone can be decreased when combined with Nilvadipine.
Seproxetine	The metabolism of Vamorolone can be decreased when combined with Seproxetine.
Linagliptin	The risk or severity of hyperglycemia can be increased when Vamorolone is combined with Linagliptin.
Indalpine	The metabolism of Vamorolone can be decreased when combined with Indalpine.
Netupitant	The metabolism of Vamorolone can be decreased when combined with Netupitant.
Barnidipine	The metabolism of Vamorolone can be decreased when combined with Barnidipine.
Benidipine	The metabolism of Vamorolone can be decreased when combined with Benidipine.
Venetoclax	The metabolism of Vamorolone can be decreased when combined with Venetoclax.
Isavuconazole	The metabolism of Vamorolone can be decreased when combined with Isavuconazole.
Fosnetupitant	The metabolism of Vamorolone can be decreased when combined with Fosnetupitant.
Berotralstat	The metabolism of Vamorolone can be decreased when combined with Berotralstat.
Pitolisant	The serum concentration of Vamorolone can be decreased when it is combined with Pitolisant.
Metreleptin	The metabolism of Vamorolone can be increased when combined with Metreleptin.
Cenobamate	The serum concentration of Vamorolone can be decreased when it is combined with Cenobamate.
Tucatinib	The metabolism of Tucatinib can be decreased when combined with Vamorolone.
Abametapir	The serum concentration of Vamorolone can be increased when it is combined with Abametapir.
Satralizumab	The serum concentration of Vamorolone can be decreased when it is combined with Satralizumab.
Sotorasib	The serum concentration of Vamorolone can be decreased when it is combined with Sotorasib.
Somatrogon	The serum concentration of the active metabolites of Vamorolone can be reduced when Vamorolone is used in combination with Somatrogon resulting in a loss in efficacy.
Mavacamten	The serum concentration of Vamorolone can be decreased when it is combined with Mavacamten.
Viloxazine	The metabolism of Vamorolone can be decreased when combined with Viloxazine.
Ivosidenib	The metabolism of Vamorolone can be increased when combined with Ivosidenib.
Dabrafenib	The serum concentration of Vamorolone can be decreased when it is combined with Dabrafenib.
Telotristat ethyl	The serum concentration of Vamorolone can be decreased when it is combined with Telotristat ethyl.
Avanafil	The serum concentration of Avanafil can be increased when it is combined with Vamorolone.

Target Protein

Glucocorticoid receptor NR3C1

Mineralocorticoid receptor NR3C2

Referensi & Sumber

Synthesis reference: Reeves EKM, Hoffman EP, Nagaraju K, Damsker JM, McCall JM: VBP15: preclinical characterization of a novel anti-inflammatory delta 9,11 steroid. Bioorg Med Chem. 2013 Apr 15;21(8):2241-2249. doi: 10.1016/j.bmc.2013.02.009. Epub 2013 Feb 18.

Artikel (PubMed)

PMID: 30745312
Heier CR, Yu Q, Fiorillo AA, Tully CB, Tucker A, Mazala DA, Uaesoontrachoon K, Srinivassane S, Damsker JM, Hoffman EP, Nagaraju K, Spurney CF: Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy. Life Sci Alliance. 2019 Feb 11;2(1):e201800186. doi: 10.26508/lsa.201800186. Print 2019 Feb.
PMID: 30742306
Mavroudis PD, van den Anker J, Conklin LS, Damsker JM, Hoffman EP, Nagaraju K, Clemens PR, Jusko WJ: Population Pharmacokinetics of Vamorolone (VBP15) in Healthy Men and Boys With Duchenne Muscular Dystrophy. J Clin Pharmacol. 2019 Jul;59(7):979-988. doi: 10.1002/jcph.1388. Epub 2019 Feb 11.
PMID: 23498916
Reeves EKM, Hoffman EP, Nagaraju K, Damsker JM, McCall JM: VBP15: preclinical characterization of a novel anti-inflammatory delta 9,11 steroid. Bioorg Med Chem. 2013 Apr 15;21(8):2241-2249. doi: 10.1016/j.bmc.2013.02.009. Epub 2013 Feb 18.

Link

Contoh Produk & Brand

Produk: 3 • International brands: 0

Produk

Agamree

Suspension • 40 mg/ml • Oral • EU • Approved
Agamree

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Agamree

Suspension • 40 mg/1mL • Oral • US • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.