Tìm theo
Bedaquiline
Các tên gọi khác (8 ) :
  • 1-(6-Bromo-2-methoxy-quinolin-3-yl)-4-dimethylamino-2-naphthalen-1-yl-1-phenyl-butan-2-ol
  • Bedaquilina
  • Bedaquilinum
  • R 207910
  • R207910
  • TMC 207
  • TMC-207
  • TMC207
antitubercular agents
Thuốc Gốc
Small Molecule
CAS: 843663-66-1
CTHH: C32H31BrN2O2
PTK: 555.505
Bedaquiline is a bactericidal antimycobacterial drug. Chemically it is a diarylquinoline. FDA approved on December 28, 2012.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C32H31BrN2O2
Phân tử khối
555.505
Monoisotopic mass
554.156890893
InChI
InChI=1S/C32H31BrN2O2/c1-35(2)19-18-32(36,28-15-9-13-22-10-7-8-14-26(22)28)30(23-11-5-4-6-12-23)27-21-24-20-25(33)16-17-29(24)34-31(27)37-3/h4-17,20-21,30,36H,18-19H2,1-3H3/t30-,32-/m1/s1
InChI Key
InChIKey=QUIJNHUBAXPXFS-XLJNKUFUSA-N
IUPAC Name
(1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-(dimethylamino)-2-(naphthalen-1-yl)-1-phenylbutan-2-ol
Traditional IUPAC Name
(1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-(dimethylamino)-2-(naphthalen-1-yl)-1-phenylbutan-2-ol
SMILES
COC1=NC2=C(C=C(Br)C=C2)C=C1[C@@H](C1=CC=CC=C1)[C@@](O)(CCN(C)C)C1=CC=CC2=C1C=CC=C2
Độ hòa tan
Insoluble
logP
7.13
logS
-6.5
pKa (strongest acidic)
13.61
pKa (Strongest Basic)
8.91
PSA
45.59 Å2
Refractivity
154.02 m3·mol-1
Polarizability
57.29 Å3
Rotatable Bond Count
8
H Bond Acceptor Count
4
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
5
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Bedaquiline is primarily subjected to oxidative metabolism leading to the formation of N-monodesmethyl metabolite (M2). M2 is not thought to contribute significantly to clinical efficacy given its lower average exposure (23% to 31%) in humans and lower antimycobacterial activity (4 to 6-fold lower) compared to the parent compound. M2 concentrations appeared to correlate with QT prolongation. Bedaquiline inhibits mycobacterial TB at a minimal inhibitory concentration (MIC) from 0.002-0.06 μg/ml and with a MIC50 of 0.03 μg/ml. Furthermore, bacteria that have smaller ATP stores (usually in dormant, nonreplicating bacilli) are more susceptible to bedaquiline.
Cơ Chế Tác Dụng : Bedaquiline is a bactericidal antimycobacterial drug. Chemically it is a diarylquinoline. FDA approved on December 28, 2012. Bedaquiline is a diarylquinoline antimycobacterial drug that inhibits the proton pump of mycobacterial ATP (adenosine 5'-triphosphate) synthase, an enzyme that is essential for the generation of energy in Mycobacterium tuberculosis. Bacterial death occurs as a result of bedaquiline.
Dược Động Học :
▧ Absorption :
Tmax, oral dose = 5 hours; Food increases the oral bioavailability. AUC increases proportionally up to the highest dose studied in healthy volunteers. When 400 mg of bedaquiline is administered once daily for a week, the peak plasma concentration (Cmax) is 5.5 μg/ml and an AUC of 64.75 μgh/ml.
▧ Volume of Distribution :
Vd, central compartment = 164 L
▧ Protein binding :
>99.9 bound to plasma proteins.
▧ Metabolism :
Bedaquiline is hepatically metabolized. The main enzyme involved is CYP3A4 which metabolizes bedaquiline into the N-monodesmethyl metabolite (M2). This metabolite is 4 to 6-times less active in terms of antimycobacterial potency.
▧ Route of Elimination :
Bedaquiline is primarily elimination in the feces. The urinary excretion of unchanged bedaquiline was < 0.001% of the dose in clinical studies, indicating that renal clearance of unchanged drug is insignificant.
▧ Half Life :
Terminal elimination half-life, bedaquiline and M2 = 5.5 months. This long half-life suggests slow release of bedaquiline and M2 from peripheral tissues.
Độc Tính : The most common adverse reactions reported in ≥10% of patients treated with bedaquiline are nausea, arthralgia, and headache.
Chỉ Định : Bedaquiline is indicated as part of combination therapy in adults (≥ 18 years) with pulmonary multi-drug resistant tuberculosis (MDR-TB).
Tương Tác Thuốc :
  • Ketoconazole Strong CYP3A4 inhibitors may increase exposure of bedaquiline. Monitor concomitant therapy closely.
  • Rifampicin Strong CYP3A4 inducers may decrease exposure of bedaquiline. Co-administration should be avoided.
Liều Lượng & Cách Dùng : Tablet - Oral - 100 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB08903
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D09872
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/59676-701-01
Wikipedia
http://en.wikipedia.org/wiki/Bedaquiline
RxList
http://www.rxlist.com/sirturo-drug.htm
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