Peringatan Keamanan

There is no experience with the treatment of acute overdose with SIRTURO. Take general measures to support basic vital functions including monitoring of vital signs and ECG (QT interval) in case of deliberate or accidental overdose. It is advisable to contact a poison control center to obtain the latest recommendations for the management of an overdose. Since bedaquiline is highly protein-bound, dialysis is not likely to significantly remove bedaquiline from plasma.^L48506

Bedaquiline was not carcinogenic in rats up to the maximum tolerated dose of 10 mg/kg/day. Exposures at this dose in rats (AUCs) were within 1-fold to 2-fold of those observed in adult patients in the clinical trials.^L48506

No mutagenic or clastogenic effects were detected in the in vitro non-mammalian reverse mutation (Ames) test, in vitro mammalian (mouse lymphoma) forward mutation assay, and an in vivo mouse bone marrow micronucleus assay.^L48506

SIRTURO did not affect fertility when evaluated in male and female rats at approximately twice the clinical exposure based on AUC comparisons. There was no effect of maternal treatment on sexual maturation, mating performance, or fertility in the F1 generation exposed to bedaquiline in utero at approximately twice the human exposure.^L48506

Bedaquiline

DB08903

small molecule approved

Deskripsi

Bedaquiline is a bactericidal antimycobacterial drug belonging to the class of diarylquinoline. The quinolinic central heterocyclic nucleus with alcohol and amine side chains is responsible for bedaquiline-mediated antimycobacterial activity.^A261866 Although it is closely related to fluoroquinolones, bedaquiline does not affect DNA gyrase; instead, bedaquiline inhibits the c subunit of ATP synthase responsible for synthesizing ATP.^A261866 Consequently, bedaquiline can be used to treat mycobacterial infection, particularly tuberculosis (TB).^L48506 Although the current standard of TB treatment of anti-TB drugs for 2 months, including 2 key drugs isoniazid and rifampin, is highly effective, the emergence of multidrug-resistant TB (MDR-TB) to isoniazid and rifampin has substantially worsened patients outcome.^A261861

Bedaquiline was approved by the FDA on December 28, 2012, to treat pulmonary MDR-TB, following favorable results in multiple pre-clinical and clinical studies.A261856,A261861 It is the first drug that was approved in the last 40 years by the FDA for TB unresponsive to current treatments on the market.^A261856 Currently, bedaquiline is the last-line anti-TB drug and must only be used in an appropriate combination regimen.L48506,A261866

Struktur Molekul 2D

Berat 555.505

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 mean terminal elimination half-life of bedaquiline and the N-monodesmethyl metabolite (M2) is approximately 5.5 months. This long terminal elimination phase likely reflects the slow release of bedaquiline and M2 from peripheral tissues.[L48506]

Volume Distribusi The volume of distribution in the central compartment is estimated to be approximately 164 Liters.[L48506]

Klirens (Clearance) Bedaquiline has a low apparent clearance of approximately 2.78 L/h.[A261836]

Absorpsi

After the recommended dosing regimen of bedaquiline (400 mg for 2 weeks followed by 200 mg three times per week for 22 weeks), the C_max and AUC_24h were calculated to be 1.659 ?g/ml and 25.863 ?g.h/ml respectively.^L48506 After a single oral dose administration of bedaquiline, maximum plasma concentrations (C_max) are typically achieved at approximately 5 hours post-dose. C_max and the area under the plasma concentration-time curve (AUC) increased proportionally up to 700 mg (1.75 times the 400 mg loading dose).^L48506 Administration of bedaquiline with a standard meal containing approximately 22 grams of fat (558 total Kcal) increased the relative bioavailability by approximately 2-fold compared to administration under fasted conditions. Bedaquiline should be taken with food to enhance its oral bioavailability.^L48506

Metabolisme

CYP3A4 was the major CYP isoenzyme involved in the in vitro metabolism of bedaquiline and the formation of the N-monodesmethyl metabolite (M2).^L48506

Rute Eliminasi

After reaching C_max, bedaquiline concentrations decline tri-exponentially. Based on preclinical studies, bedaquiline is mainly excreted in feces. The urinary excretion of unchanged bedaquiline was less than or equal to 0.001% of the dose in clinical studies, indicating that renal clearance of unchanged drug is insignificant.^L48506

Interaksi Makanan

2 Data

1. Avoid alcohol.
2. Take with food. Food significantly increases the oral bioavailability.

Interaksi Obat

518 Data

Ivabradine	The risk or severity of QTc prolongation can be increased when Ivabradine is combined with Bedaquiline.
Picosulfuric acid	The therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Bedaquiline.
Ethanol	Ethanol may increase the hepatotoxic activities of Bedaquiline.
Citalopram	The risk or severity of QTc prolongation can be increased when Bedaquiline is combined with Citalopram.
Anagrelide	The risk or severity of QTc prolongation can be increased when Anagrelide is combined with Bedaquiline.
Disopyramide	The risk or severity of QTc prolongation can be increased when Disopyramide is combined with Bedaquiline.
Clemastine	The risk or severity of QTc prolongation can be increased when Clemastine is combined with Bedaquiline.
Ibutilide	The risk or severity of QTc prolongation can be increased when Ibutilide is combined with Bedaquiline.
Valproic acid	The risk or severity of QTc prolongation can be increased when Valproic acid is combined with Bedaquiline.
Grepafloxacin	The risk or severity of QTc prolongation can be increased when Grepafloxacin is combined with Bedaquiline.
Quinine	The risk or severity of QTc prolongation can be increased when Quinine is combined with Bedaquiline.
Sotalol	The risk or severity of QTc prolongation can be increased when Sotalol is combined with Bedaquiline.
Erlotinib	The risk or severity of QTc prolongation can be increased when Erlotinib is combined with Bedaquiline.
Toremifene	The risk or severity of QTc prolongation can be increased when Toremifene is combined with Bedaquiline.
Imatinib	The risk or severity of QTc prolongation can be increased when Imatinib is combined with Bedaquiline.
Thioridazine	The risk or severity of QTc prolongation can be increased when Thioridazine is combined with Bedaquiline.
Trovafloxacin	The risk or severity of QTc prolongation can be increased when Trovafloxacin is combined with Bedaquiline.
Mifepristone	The risk or severity of QTc prolongation can be increased when Mifepristone is combined with Bedaquiline.
Cocaine	The risk or severity of QTc prolongation can be increased when Cocaine is combined with Bedaquiline.
Procainamide	The risk or severity of QTc prolongation can be increased when Procainamide is combined with Bedaquiline.
Arsenic trioxide	The risk or severity of QTc prolongation can be increased when Arsenic trioxide is combined with Bedaquiline.
Escitalopram	The risk or severity of QTc prolongation can be increased when Escitalopram is combined with Bedaquiline.
Domperidone	The risk or severity of QTc prolongation can be increased when Domperidone is combined with Bedaquiline.
Sparfloxacin	The risk or severity of QTc prolongation can be increased when Sparfloxacin is combined with Bedaquiline.
Halofantrine	The risk or severity of QTc prolongation can be increased when Halofantrine is combined with Bedaquiline.
Bepridil	The risk or severity of QTc prolongation can be increased when Bepridil is combined with Bedaquiline.
Paliperidone	The risk or severity of QTc prolongation can be increased when Paliperidone is combined with Bedaquiline.
Lithium cation	The risk or severity of QTc prolongation can be increased when Lithium cation is combined with Bedaquiline.
Temafloxacin	The risk or severity of QTc prolongation can be increased when Temafloxacin is combined with Bedaquiline.
Zuclopenthixol	The risk or severity of QTc prolongation can be increased when Zuclopenthixol is combined with Bedaquiline.
Tetrabenazine	The risk or severity of QTc prolongation can be increased when Tetrabenazine is combined with Bedaquiline.
Iloperidone	The risk or severity of QTc prolongation can be increased when Iloperidone is combined with Bedaquiline.
Vandetanib	The risk or severity of QTc prolongation can be increased when Vandetanib is combined with Bedaquiline.
Romidepsin	The risk or severity of QTc prolongation can be increased when Romidepsin is combined with Bedaquiline.
Asenapine	The risk or severity of QTc prolongation can be increased when Asenapine is combined with Bedaquiline.
Artemether	The risk or severity of QTc prolongation can be increased when Artemether is combined with Bedaquiline.
Lumefantrine	The risk or severity of QTc prolongation can be increased when Lumefantrine is combined with Bedaquiline.
Vemurafenib	The risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Bedaquiline.
Glasdegib	The risk or severity of QTc prolongation can be increased when Bedaquiline is combined with Glasdegib.
Deutetrabenazine	The risk or severity of QTc prolongation can be increased when Deutetrabenazine is combined with Bedaquiline.
Macimorelin	The risk or severity of QTc prolongation can be increased when Macimorelin is combined with Bedaquiline.
Terodiline	The risk or severity of QTc prolongation can be increased when Terodiline is combined with Bedaquiline.
Dofetilide	The risk or severity of QTc prolongation can be increased when Dofetilide is combined with Bedaquiline.
Cisapride	The risk or severity of QTc prolongation can be increased when Cisapride is combined with Bedaquiline.
Astemizole	The risk or severity of QTc prolongation can be increased when Astemizole is combined with Bedaquiline.
Quinidine	The risk or severity of QTc prolongation can be increased when Quinidine is combined with Bedaquiline.
Pimozide	The risk or severity of QTc prolongation can be increased when Pimozide is combined with Bedaquiline.
Dronedarone	The risk or severity of QTc prolongation can be increased when Dronedarone is combined with Bedaquiline.
Eliglustat	The risk or severity of QTc prolongation can be increased when Eliglustat is combined with Bedaquiline.
Leuprolide	The risk or severity of QTc prolongation can be increased when Leuprolide is combined with Bedaquiline.
Goserelin	The risk or severity of QTc prolongation can be increased when Goserelin is combined with Bedaquiline.
Erythromycin	The serum concentration of Bedaquiline can be increased when it is combined with Erythromycin.
Azithromycin	The risk or severity of QTc prolongation can be increased when Azithromycin is combined with Bedaquiline.
Moxifloxacin	The risk or severity of QTc prolongation can be increased when Moxifloxacin is combined with Bedaquiline.
Ranolazine	The risk or severity of QTc prolongation can be increased when Ranolazine is combined with Bedaquiline.
Sulfisoxazole	The risk or severity of QTc prolongation can be increased when Sulfisoxazole is combined with Bedaquiline.
Methadone	The risk or severity of QTc prolongation can be increased when Methadone is combined with Bedaquiline.
Diltiazem	The risk or severity of QTc prolongation can be increased when Diltiazem is combined with Bedaquiline.
Clozapine	The risk or severity of QTc prolongation can be increased when Bedaquiline is combined with Clozapine.
Sulpiride	The risk or severity of QTc prolongation can be increased when Sulpiride is combined with Bedaquiline.
Nimodipine	The risk or severity of QTc prolongation can be increased when Nimodipine is combined with Bedaquiline.
Promazine	The risk or severity of QTc prolongation can be increased when Promazine is combined with Bedaquiline.
Prochlorperazine	The risk or severity of QTc prolongation can be increased when Prochlorperazine is combined with Bedaquiline.
Droperidol	The risk or severity of QTc prolongation can be increased when Droperidol is combined with Bedaquiline.
Chlorpromazine	The risk or severity of QTc prolongation can be increased when Chlorpromazine is combined with Bedaquiline.
Oxaliplatin	The risk or severity of QTc prolongation can be increased when Oxaliplatin is combined with Bedaquiline.
Ciprofloxacin	The risk or severity of QTc prolongation can be increased when Ciprofloxacin is combined with Bedaquiline.
Fluorouracil	The risk or severity of QTc prolongation can be increased when Fluorouracil is combined with Bedaquiline.
Perflutren	The risk or severity of QTc prolongation can be increased when Perflutren is combined with Bedaquiline.
Cinnarizine	The risk or severity of QTc prolongation can be increased when Cinnarizine is combined with Bedaquiline.
Atropine	The risk or severity of QTc prolongation can be increased when Atropine is combined with Bedaquiline.
Chloroquine	The risk or severity of QTc prolongation can be increased when Chloroquine is combined with Bedaquiline.
Adenosine	The risk or severity of QTc prolongation can be increased when Adenosine is combined with Bedaquiline.
Pentamidine	The risk or severity of QTc prolongation can be increased when Pentamidine is combined with Bedaquiline.
Gadobenic acid	The risk or severity of QTc prolongation can be increased when Gadobenic acid is combined with Bedaquiline.
Carbinoxamine	The risk or severity of QTc prolongation can be increased when Carbinoxamine is combined with Bedaquiline.
Dolasetron	The risk or severity of QTc prolongation can be increased when Dolasetron is combined with Bedaquiline.
Roxithromycin	The risk or severity of QTc prolongation can be increased when Roxithromycin is combined with Bedaquiline.
Nalidixic acid	The risk or severity of QTc prolongation can be increased when Nalidixic acid is combined with Bedaquiline.
Cinoxacin	The risk or severity of QTc prolongation can be increased when Cinoxacin is combined with Bedaquiline.
Granisetron	The risk or severity of QTc prolongation can be increased when Granisetron is combined with Bedaquiline.
Ondansetron	The risk or severity of QTc prolongation can be increased when Ondansetron is combined with Bedaquiline.
Levosimendan	The risk or severity of QTc prolongation can be increased when Levosimendan is combined with Bedaquiline.
Mesoridazine	The risk or severity of QTc prolongation can be increased when Mesoridazine is combined with Bedaquiline.
Desloratadine	The risk or severity of QTc prolongation can be increased when Desloratadine is combined with Bedaquiline.
Lomefloxacin	The risk or severity of QTc prolongation can be increased when Lomefloxacin is combined with Bedaquiline.
Dimenhydrinate	The risk or severity of QTc prolongation can be increased when Dimenhydrinate is combined with Bedaquiline.
Primaquine	The risk or severity of QTc prolongation can be increased when Primaquine is combined with Bedaquiline.
Papaverine	The risk or severity of QTc prolongation can be increased when Papaverine is combined with Bedaquiline.
Chlorpheniramine	The risk or severity of QTc prolongation can be increased when Chlorpheniramine is combined with Bedaquiline.
Nifedipine	The risk or severity of QTc prolongation can be increased when Nifedipine is combined with Bedaquiline.
Levofloxacin	The risk or severity of QTc prolongation can be increased when Levofloxacin is combined with Bedaquiline.
Gemifloxacin	The risk or severity of QTc prolongation can be increased when Gemifloxacin is combined with Bedaquiline.
Ofloxacin	The risk or severity of QTc prolongation can be increased when Ofloxacin is combined with Bedaquiline.
Propafenone	The risk or severity of QTc prolongation can be increased when Propafenone is combined with Bedaquiline.
Flecainide	The risk or severity of QTc prolongation can be increased when Flecainide is combined with Bedaquiline.
Probucol	The risk or severity of QTc prolongation can be increased when Probucol is combined with Bedaquiline.
Aceprometazine	The risk or severity of QTc prolongation can be increased when Aceprometazine is combined with Bedaquiline.
Terlipressin	The risk or severity of QTc prolongation can be increased when Terlipressin is combined with Bedaquiline.
Prenylamine	The risk or severity of QTc prolongation can be increased when Prenylamine is combined with Bedaquiline.

Target Protein

ATP synthase subunit c atpE

Referensi & Sumber

Artikel (PubMed)

PMID: 20521931
Matteelli A, Carvalho AC, Dooley KE, Kritski A: TMC207: the first compound of a new class of potent anti-tuberculosis drugs. Future Microbiol. 2010 Jun;5(6):849-58. doi: 10.2217/fmb.10.50.
PMID: 24957842
McLeay SC, Vis P, van Heeswijk RP, Green B: Population pharmacokinetics of bedaquiline (TMC207), a novel antituberculosis drug. Antimicrob Agents Chemother. 2014 Sep;58(9):5315-24. doi: 10.1128/AAC.01418-13. Epub 2014 Jun 23.
PMID: 23776831
Mahajan R: Bedaquiline: First FDA-approved tuberculosis drug in 40 years. Int J Appl Basic Med Res. 2013 Jan;3(1):1-2. doi: 10.4103/2229-516X.112228.
PMID: 25134476
Fox GJ, Menzies D: A Review of the Evidence for Using Bedaquiline (TMC207) to Treat Multi-Drug Resistant Tuberculosis. Infect Dis Ther. 2013 Dec;2(2):123-44. doi: 10.1007/s40121-013-0009-3. Epub 2013 Aug 2.
PMID: 33684606
Khoshnood S, Goudarzi M, Taki E, Darbandi A, Kouhsari E, Heidary M, Motahar M, Moradi M, Bazyar H: Bedaquiline: Current status and future perspectives. J Glob Antimicrob Resist. 2021 Jun;25:48-59. doi: 10.1016/j.jgar.2021.02.017. Epub 2021 Mar 5.

Link

Contoh Produk & Brand

Produk: 5 • International brands: 0

Produk

Sirturo

Tablet • 20 mg/1 • Oral • US • Approved
Sirturo

Tablet • 100 mg/1 • Oral • US • Approved
Sirturo

Tablet • 100 mg • Oral • EU • Approved
Sirturo

Tablet • 100 mg • Oral • EU • Approved
Sirturo

Tablet • 20 mg • Oral • EU • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.