Tìm theo
Zidovudine
Các tên gọi khác (5 ) :
  • Azidothymidine
  • AZT
  • ZDV
  • Zidovudin
  • Zidovudinum
Thuốc trị ký sinh trùng, chống nhiễm khuẩn
Thuốc Gốc
Small Molecule
CAS: 30516-87-1
ATC: J05AF01
ĐG : Amerisource Health Services Corp. , http://www.amerisourcebergen.com
CTHH: C10H13N5O4
PTK: 267.2413
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. [PubChem]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
Phân tử khối
267.2413
Monoisotopic mass
267.096753929
InChI
InChI=1S/C10H13N5O4/c1-5-3-15(10(18)12-9(5)17)8-2-6(13-14-11)7(4-16)19-8/h3,6-8,16H,2,4H2,1H3,(H,12,17,18)/t6-,7+,8+/m0/s1
InChI Key
InChIKey=HBOMLICNUCNMMY-XLPZGREQSA-N
IUPAC Name
1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
Traditional IUPAC Name
zidovudine
SMILES
CC1=CN([[email protected]]2C[[email protected]](N=[N+]=[N-])[[email protected]@H](CO)O2)C(=O)NC1=O
Độ tan chảy
113-115 °C
Độ hòa tan
2.01E+004 mg/L (at 25 °C)
logP
0.05
logS
-1.2
pKa (strongest acidic)
9.96
pKa (Strongest Basic)
-3
PSA
108.3 Å2
Refractivity
61.7 m3·mol-1
Polarizability
24.93 Å3
Rotatable Bond Count
3
H Bond Acceptor Count
6
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
2
Bioavailability
1
Rule of Five
true
Ghose Filter
true
caco2 Permeability
-5.16
Dược Lực Học : Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Zidovudine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.
Cơ Chế Tác Dụng : A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. [PubChem] Zidovudine, a structural analog of thymidine, is a prodrug that must be phosphorylated to its active 5′-triphosphate metabolite, zidovudine triphosphate (ZDV-TP). It inhibits the activity of HIV-1 reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue. It competes with the natural substrate dGTP and incorporates itself into viral DNA. It is also a weak inhibitor of cellular DNA polymerase α and γ.
Dược Động Học :
▧ Absorption :
Rapid and nearly complete absorption from the gastrointestinal tract following oral administration; however, because of first-pass metabolism, systemic bioavailability of zidovudine capsules and solution is approximately 65% (range, 52 to 75%). Bioavailability in neonates up to 14 days of age is approximately 89%, and it decreases to approximately 61% and 65% in neonates over 14 days of age and children 3 months to 12 years, respectively. Administration with a high-fat meal may decrease the rate and extent of absorption.
▧ Volume of Distribution :
Apparent volume of distribution, HIV-infected patients, IV administration = 1.6 ± 0.6 L/kg
▧ Protein binding :
30-38%
▧ Metabolism :
Hepatic. Metabolized by glucuronide conjugation to major, inactive metabolite, 3′-azido-3′-deoxy-5′- O-beta-D-glucopyranuronosylthymidine (GZDV). UGT2B7 is the primary UGT isoform that is responsible for glucuronidation. Compared to zidovudine, GZDV's area under the curve is approximately 3-fold greater. The cytochrome P450 isozymes are responsible for the reduction of the azido moiety to form 3'-amino-3'- deoxythymidine (AMT).
▧ Route of Elimination :
As in adult patients, the major route of elimination was by metabolism to GZDV. After intravenous dosing, about 29% of the dose was excreted in the urine unchanged and about 45% of the dose was excreted as GZDV.
▧ Half Life :
Elimination half life, HIV-infected patients, IV administration = 1.1 hours (range of 0.5 - 2.9 hours)
▧ Clearance :
* 0.65 +/- 0.29 L/hr/kg [HIV-infected, Birth to 14 Days of Age] * 1.14 +/- 0.24 L/hr/kg [HIV-infected, 14 Days to 3 Months of Age] * 1.85 +/- 0.47 L/hr/kg [HIV-infected, 3 Months to 12 Years of Age]. The transporters, ABCB1, ABCC4, ABCC5, and ABCG2 are involved with the clearance of zidovudine.
Độc Tính : Symptoms of overdose include fatigue, headache, nausea, and vomiting. LD50 is 3084 mg/kg (orally in mice).
Chỉ Định : Used in combination with other antiretroviral agents for the treatment of human immunovirus (HIV) infections.
Tương Tác Thuốc :
  • Atovaquone Atovaquone increases the effect and toxicity of zidovudine
  • Clarithromycin Clarithromycin may decrease the serum concentration of zidovudine. Increased myelosuppression in mice has been observed. Consider staggering doses during concomitant therapy and closely monitor response to zidovudine therapy.
  • Doxorubicin Additive myelosuppression may occur. Doxorubicin may decrease the efficacy of zidovudine. Concomitant therapy should be avoided.
  • Ganciclovir Increased risk of hematologic toxicity. Concomitant therapy should be avoided.
  • Interferon beta-1b The interferon increases the effect and toxicity of zidovudine
  • Methadone Methadone increases the effect and toxicity of zidovudine
  • Probenecid Rash, malaise, myalgia
  • Ribavirin Increased risk or severity of anemia. Consider alternate therapy or monitor more closely for anemia.
  • Rifabutin The rifamycin decreases levels of zidovudine
  • Rifampicin Rifampin may decrease the serum concentration of zidovudine by increasing its metabolism. Monitor for changes in the serum concentration and therapeutic and adverse effects of zidovudine if rifampin is initiated, discontinued or dose changed.
  • Rifapentine Rifapentin may decrease the serum concentration of zidovudine by increasing its metabolism. Monitor for changes in the serum concentration and therapeutic and adverse effects of zidovudine if rifapentin is initiated, discontinued or dose changed.
  • Stavudine Zidovudine may decrease the efficacy of stavudine. Concomitant therapy should be avoided.
  • Tipranavir Tipranavir decreases the concentration of Zidovudine.
  • Valganciclovir The adverse/toxic effects of Zidovudine, a reverse transcriptase inhibitor (nucleoside), may be enhanced by Valganciclovir. There is a significant risk of hematologic toxicity. Concomitant therapy should be avoided.
Liều Lượng & Cách Dùng : Capsule - Oral - 100 mg
Injection, solution - Intravenous - 10 mg/mL
Syrup - Oral - 50 mg/5 mL
Tablet - Oral - 300 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Retrovir
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