Tìm theo
Dolutegravir
Thuốc Gốc
Small Molecule
CAS: 1051375-16-6
CTHH: C20H19F2N3O5
PTK: 419.3788
Dolutegravir is indicated for HIV-1 infection for adults and children and adolescents ≥12 years of age and weighing ≥40 kg. It is marketed as Tivicay as dolutegravir sodium. 52.6 mg of dolutegravir sodium is equivalent to 50 mg dolutegravir free acid. FDA approved on August 12, 2013.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C20H19F2N3O5
Phân tử khối
419.3788
Monoisotopic mass
419.129277143
InChI
InChI=1/C20H19F2N3O5/c1-10-4-5-30-15-9-24-8-13(17(26)18(27)16(24)20(29)25(10)15)19(28)23-7-11-2-3-12(21)6-14(11)22/h2-3,6,8,10,15,27H,4-5,7,9H2,1H3,(H,23,28)/t10-,15+/s2
InChI Key
InChIKey=RHWKPHLQXYSBKR-PJJZDBKBNA-N
IUPAC Name
(3S,7R)-N-[(2,4-difluorophenyl)methyl]-11-hydroxy-7-methyl-9,12-dioxo-4-oxa-1,8-diazatricyclo[8.4.0.0³,⁸]tetradeca-10,13-diene-13-carboxamide
Traditional IUPAC Name
(3S,7R)-N-[(2,4-difluorophenyl)methyl]-11-hydroxy-7-methyl-9,12-dioxo-4-oxa-1,8-diazatricyclo[8.4.0.0³,⁸]tetradeca-10,13-diene-13-carboxamide
SMILES
[H][C@]12CN3C=C(C(=O)NCC4=CC=C(F)C=C4F)C(=O)C(O)=C3C(=O)N1[C@H](C)CCO2
Độ hòa tan
Slightly soluble
logP
1.1
logS
-3.7
pKa (strongest acidic)
8.7
pKa (Strongest Basic)
0.28
PSA
99.18 Å2
Refractivity
102.77 m3·mol-1
Polarizability
39.99 Å3
Rotatable Bond Count
3
H Bond Acceptor Count
6
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
4
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : HIV-1 infected subjects on dolutegravir monotherapy demonstrated rapid and dose-dependent antiviral activity with mean declines from baseline to Day 11 in HIV-1 RNA of 1.5, 2.0, and 2.5 log10 for dolutegravir 2 mg, 10 mg, and 50 mg once daily, respectively. Antiviral response was maintained for 3 to 4 days after the last 50 mg dose. Dolutegravir did not prolong the QTc interval over 24 hours postdose. The maximum mean QTc change based on Fridericia correction method (QTcF) for dolutegravir was 2.4 msec (1-sided 95% upper CI: 4.9 msec). Those given a 50 mg once daily dose of dolutegravir also experienced a decrease in creatinine clearance as determined by 24-hour urine collection after 14 days. There is no significant effect on actual glomerular filtration rate or renal plasma flow compared to placebo.
Cơ Chế Tác Dụng : Dolutegravir is indicated for HIV-1 infection for adults and children and adolescents ≥12 years of age and weighing ≥40 kg. It is marketed as Tivicay as dolutegravir sodium. 52.6 mg of dolutegravir sodium is equivalent to 50 mg dolutegravir free acid. FDA approved on August 12, 2013. Dolutegravir is an HIV-1 antiviral agent. It inhibits HIV integrase by binding to the active site and blocking the strand transfer step to retroviral DNA integration. This is an essential step of the HIV replication cycle and will result in an inhibition of viral activity. Dolutegravir has a mean EC50 value of 0.5 nM (0.21 ng/mL) to 2.1 nM (0.85 ng/mL) in peripheral blood mononuclear cells (PBMCs) and MT-4 cells.
Dược Động Học :
▧ Absorption :
When 50 mg of dolutegravir once daily was orally administered to HIV-1 infected adults, the AUC (0-24), Cmax, and Cmin is 53.6 mcg.h/mL, 3.67 mcg/mL, and 1.11 mcg/mL, respectively. The peak plasma concentration was observed 2 to 3 hours post dose. Steady state is achieved within approximately 5 days with average accumulation ratios for AUC, Cmax, and C24h ranging from 1.2 to 1.5. When 50 mg once daily is given to pediatric patients (12 to <18 years and weighing ≥40 kg) the Cmax, AUC (0-24), and C24 is 3.49 mcg/mL, 46 mcg.h/mL, and 0.90 mcg/mL respectively.
▧ Volume of Distribution :
Volume of distribution (Vd/F), 50 mg once daily = 17.4 L. The median dolutegravir concentration in the CSF was 18 ng/mL after 2 weeks of treatment.
▧ Protein binding :
Dolutegravir is highly protein bound (≥98.9%) to human plasma proteins.
▧ Metabolism :
Dolutegravir is primarily metabolized by UGT1A1 with some minor contributed CYP3A.
▧ Route of Elimination :
When a single oral dose of dolutegravir is given, 53% was excreted unchanged in the feces. 31% is excreted in urine in which consists of the ether glucuronide of dolutegravir (18.9%), a metabolite formed by oxidation at the benzylic carbon (3.0%), and its hydrolytic N-dealkylation product (3.6%). Renal elimination of unchanged drug was low (<1%).
▧ Half Life :
Terminal half life = 14 hours
▧ Clearance :
Apparent clearance (CL/F) = 1.0 L/h
Độc Tính : The most common adverse reactions of moderate to severe intensity and incidence ≥2% (in those receiving TIVICAY in any one adult trial) are insomnia and headache.
Chỉ Định : Dolutegravir is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and children aged 12 years and older and weighing at least 40 kg.
Liều Lượng & Cách Dùng : Tablet - Oral - 50 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB08930
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D10066
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/49702-228-13
Wikipedia
http://en.wikipedia.org/wiki/Dolutegravir
Drugs.com
http://www.drugs.com/cdi/dolutegravir.html
... loading
... loading