zidovudine; azidothymidine; AZT; BW A509U; Zydowin


GlaxoSmithKline (GSK; global presence)

Type of product:


Viral family:



Approved for market in US (Mar. 19, 1987) and other markets


Structure Retrovir  C10H13N5O4



Molecular weight:



Synonyms:zidovudine; azidothymidine; AZT; BW A509U; Zydowin       Sponsor:GlaxoSmithKline (GSK; global presence)       Type of product:Inhibitor       Mode of action:NRTI       Viral family:Retroviridae       Virus:HIV (Human Immunodeficiency virus)      


Small molecule, inhibitor of HIV RT enzyme;
Converted to active drug AZT-triphosphate by cell enzymes;
Inhibits viral RT by competing with natural substrate deoxythymidine triphosphate and by incorporation into nascent viral DNA, effectively blocking chain elongation;
Most affected cell enzymes are DNA polymerase α and mitochondrial DNA polymerase γ
PK Data, Dosage or Route of Administration:
Main metabolic pathway through glucuronidation in liver;
Oral bioavailability approx. 65%, with CNS and placenta penetration;
Low level of binding to plasma proteins;

Can be administered with and without food;

Oral dose is 600 mg per day (adult);

Also available as syrup

Resistance experts consider Zidovudine resistance to be associated with RT mutations M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E, known as TAMs;
Cross-resistance with Stavudine;
Primer unblocking mechanism proposed to explain AZT resistance associated with RT mutant D67N/K70R/T215Y/K219Q;

Co-administration with 3TC has been shown to delay resistance to AZT, and resensitization to AZT has been reported in pts with strains initially resistant to AZT, further treated with 3TC;


Data published in Dec. 2007 by Yap et al. (PLoS Medicine, 2007, 4[12]: e335.doi:10.1371/journal.pmed.0040335) suggest that RT mutation N348I in the C-terminal region could play a significant role in Azidothymidine and Nevirapine resistance
In vivo and clinical data:
Side effects: initial nausea, headache, fatigue, anemia, neutropenia, neuropathy, myopathy; 
Common side effects include headache, anorexia, nausea and vomiting,
Most serious AZT-related side effects : anemia, leukopenia (these effects can be exacerbated with co-administration of bone marrow-suppressive and cytotoxic agents);
Other significant potential side effects include lactic acidosis and hepatomegaly with steatosis including fatal cases (also seen with other nucleoside analogues, alone or in combination); 
Induction of tumors in animals at high doses;

Positive in mutagenesis assays, and embryotoxic at high doses in animal studies

Activity in vitro

Ki: 7 nM (enzyme inhibition)
EC50: 11 nM to 50 nM

CCIC50: 1 to 10 μM (depending on types of cells)

Development status

Approved for market in US (Mar. 19, 1987) and other markets


Nucleoside analogue of pyrimidine (thymidine);
First ever anti-HIV drug on the market;
First synthesized at the Michigan Cancer Foundation (1964);
First antiretroviral activity shown at Max Planck Institute (1974) with mouse retrovirus in vitro;
PK and anti-HIV activity studies, including first administration to AIDS patient performed by National Cancer Institute and Duke University;
Patented by Burroughs-Wellcome (now part of GlaxoSmithKline) for use as HIV/AIDS drug;

Now approved for use in combination with other antiretroviral drugs in the treatment of HIV infection, including prevention of maternal-fetal transmission of HIV;

Other formulation approved in 1989, followed by other approbations: 1990 (dose adjustment), 1994 (prevention of perinatal transmission mother-to-child);
Generic versions of zidovudine produced by Ranbaxy Laboratories (July 2005), Aurobindo Pharma (Sept. 2005), and Roxane Laboratories have been FDA-approved in 2005 for US market and other countries, with emphasis on developing countries where they will be available for purchase under US PEPFAR plan;

On June 30, 2006, FDA granted tentative approval to fixed-dose tablet containing generic zidovudine, lamivudine and nevirapine made by Aurobindo;

Also sold under name Zydowin by Zydus Biogen

Other generic versions have reached market in several countries

Patent infos

All patents for AZT as anti-HIV drug expired in 2005:

US Patent 4724232, exp. date Sept. 17, 2005
US Patent 4818538, exp. date Sept. 17, 2005
US Patent 4828838, exp. date Sept. 17, 2005
US Patent 4833130, exp. date Sept. 17, 2005
US Patent 4837208, exp. date Sept. 17, 2005

Formula: C10H13N5O4
Molecular weight: 267.24