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Identification
Name Zidovudine
Accession Number DB00495 (APRD00449)
Type small molecule
Groups approved
Description

A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group.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]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Apo-Zidovudine
  • Azidothymidine
  • Aztec
  • Compound S
  • Novo-Azt
  • Retrovir
  • Zidovudine EP III
Brand name mixtures
  • Combivir (Lamivudine + Zidovudine)
  • Trizivir (Abacavir sulfate + Lamivudine + Zidovudine)
Categories
  • Anti-HIV Agents
  • Antimetabolites
  • Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
  • Reverse Transcriptase Inhibitors
CAS number 30516-87-1
Weight Average: 267.2413
Monoisotopic: 267.096753929
Chemical Formula C10H13N5O4
InChI Key InChIKey=HBOMLICNUCNMMY-XLPZGREQSA-N
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
Plain Text
IUPAC Name
1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
SMILES
CC1=CN([C@H]2C[C@H](N=[N+]=[N-])[C@@H](CO)O2)C(=O)NC1=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Pyrimidines and Derivatives
Substructures
  • Hydroxy Compounds
  • Ethers
  • Azides
  • Alcohols and Polyols
  • Pyrimidines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Furans
  • Cyanamides
Pharmacology
Indication For the treatment of human immunovirus (HIV) infections.
Pharmacodynamics 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.
Mechanism of action Zidovudine, a structural analog of thymidine, inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.
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 Not Available
Protein binding 30-38%
Metabolism

Hepatic. Metabolized by glucuronide conjugation to major, inactive metabolite, 3′-azido-3′-deoxy-5′- O-beta-D-glucopyranuronosylthymidine (GZDV).
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 0.5-3 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]
Toxicity Symptoms of overdose include fatigue, headache, nausea, and vomiting. LD50 is 3084 mg/kg (orally in mice).
Affected organisms
  • Human Immunodeficiency Virus
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Viiv healthcare co
  • Aurobindo pharma ltd inc
  • Cipla ltd
  • Pharmaforce inc
  • Aurobindo pharma ltd
  • Hetero drugs ltd unit iii
  • Matrix laboratories ltd
  • Ranbaxy laboratories ltd
  • Roxane laboratories inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Liquid Intravenous
Syrup Oral
Prices
Unit description Cost Unit
Retrovir 50 mg/5ml Syrup 240ml Bottle 74.11 USD bottle
Retrovir 300 mg tablet 9.1 USD tablet
Zidovudine 300 mg tablet 6.17 USD tablet
Retrovir 100 mg capsule 3.09 USD capsule
Retrovir iv infusion vial 1.61 USD ml
Patents
Country Patent Number Approved Expires
Canada 2216634 2004-07-20 2016-03-28
Canada 2105487 2002-09-24 2012-03-05
Properties
State solid
Melting point 106-112 oC
Experimental Properties
Property Value Source
water solubility 10-50 g/L at 17 oC PhysProp
logP 0.05 PhysProp
Caco2 permeability -5.16 [ADME Research, USCD] BiGG
Predicted Properties
Property Value Source
water solubility 1.63e+01 g/l ALOGPS
logP -0.10 ALOGPS
logP -0.57 ChemAxon Molconvert
logS -1.21 ALOGPS
pKa 9.96 ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 108.30 ChemAxon Molconvert
rotatable bond count 3 ChemAxon Molconvert
refractivity 61.70 ChemAxon Molconvert
polarizability 24.93 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. De Clercq E: HIV resistance to reverse transcriptase inhibitors. Biochem Pharmacol. 1994 Jan 20;47(2):155-69. Pubmed
  2. Yarchoan R, Mitsuya H, Broder S: AIDS therapies. Sci Am. 1988 Oct;259(4):110-9. Pubmed
  3. Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O’Sullivan MJ, VanDyke R, Bey M, Shearer W, Jacobson RL, et al.: Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994 Nov 3;331(18):1173-80. Pubmed
  4. Mitsuya H, Yarchoan R, Broder S: Molecular targets for AIDS therapy. Science. 1990 Sep 28;249(4976):1533-44. Pubmed
  5. Mitsuya H, Weinhold KJ, Furman PA, St Clair MH, Lehrman SN, Gallo RC, Bolognesi D, Barry DW, Broder S: 3’-Azido-3’-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7096-100. Pubmed
External Links
Resource Link
KEGG Drug D00413 Link_out
KEGG Compound C07210 Link_out
PubChem Compound 35370 Link_out
PubChem Substance 46508240 Link_out
ChemSpider 32555 Link_out
BindingDB 50002692 Link_out
ChEBI 10110 Link_out
ChEMBL 10110 Link_out
Therapeutic Targets Database DAP000701 Link_out
PharmGKB PA451954 Link_out
Drug Product Database 1946323 Link_out
RxList http://www.rxlist.com/cgi/generic3/zidovud.htm Link_out
Drugs.com http://www.drugs.com/cdi/zidovudine.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/ret1375.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Zidovudine Link_out
ATC Codes
  • J05AF01
AHFS Codes
  • 08:18.08.20
PDB Entries Not Available
FDA label show (217 KB)
MSDS show (57.2 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Reverse transcriptase

Pharmacological action: yes
Actions: inhibitor
UniProt ID: Q5DNL9 Link_out

References:
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  2. Barry M, Gibbons S, Back D, Mulcahy F: Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations. Clin Pharmacokinet. 1997 Mar;32(3):194-209. Pubmed
  3. De Clercq E: Antiretroviral drugs. Curr Opin Pharmacol. 2010 May 12. Pubmed
Enzymes

1. Cytochrome P450 2A6

Actions: substrate

Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase

UniProt ID: P11509 Link_out
Gene: CYP2A6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C19

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2C8

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2C9

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Carriers

1. Serum albumin

Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood

UniProt ID: P02768 Link_out
Gene: ALB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Quevedo MA, Moroni GN, Brinon MC: Human serum albumin binding of novel antiretroviral nucleoside derivatives of AZT. Biochem Biophys Res Commun. 2001 Nov 9;288(4):954-60. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:04

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.