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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A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group.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
Salts Not Available
Brand names
Name Company
Apo-Zidovudine
Azidothymidine
Aztec
Compound S
Novo-Azt
Retrovir
Zidovudine EP III
Brand mixtures
Brand Name Ingredients
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).

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Zidovudine
    		3'-azido-3'-deoxy-5'- O-beta-D-glucopyranuronosylthymidine Details
    Zidovudine
      		3’-amino-3’-deoxythimidine Details
      Zidovudine
        		3’-amino-3’-deoxythimidine glucuronide Details
        Zidovudine
          		5’glucuronyl zidovudine Details
          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
          DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
          Patents
          Country Patent Number Approved Expires (estimated)
          Canada 2216634 2004-07-20 2016-03-28
          Canada 2105487 2002-09-24 2012-03-05
          Properties
          State solid
          Experimental Properties
          Property Value Source
          melting point 113-115 °C PhysProp
          water solubility 2.01E+004 mg/L (at 25 °C) PHYSICIANS DESK REFERENCE (2003)
          logP 0.05 HANSCH,C ET AL. (1995)
          Caco2 permeability -5.16 ADME Research, USCD
          Predicted Properties
          Property Value Source
          water solubility 1.63e+01 g/l ALOGPS
          logP -0.1 ALOGPS
          logP -0.3 ChemAxon
          logS -1.2 ALOGPS
          pKa (strongest acidic) 9.96 ChemAxon
          pKa (strongest basic) -3 ChemAxon
          physiological charge 0 ChemAxon
          hydrogen acceptor count 6 ChemAxon
          hydrogen donor count 2 ChemAxon
          polar surface area 108.3 ChemAxon
          rotatable bond count 3 ChemAxon
          refractivity 61.7 ChemAxon
          polarizability 24.93 ChemAxon
          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
          Drug Interaction
          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
          Rifampin 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.
          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
          2. Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. Pubmed
          3. Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. Pubmed
          4. Letter: Exercise testing and coronary heart disease. N Engl J Med. 1975 Dec 4;293(23):1208-10. Pubmed
          5. Letter: Exercise testing and coronary heart disease. N Engl J Med. 1975 Dec 4;293(23):1208-10. 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
          Transporters

          1. Solute carrier family 22 member 2

          Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity

          UniProt ID: O15244 Link_out
          Gene: SLC22A2 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Urakami Y, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002 Jul;13(7):1703-10. Pubmed

          2. Solute carrier family 22 member 6

          UniProt ID: Q4U2R8 Link_out
          Gene: hROAT1 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Wada S, Tsuda M, Sekine T, Cha SH, Kimura M, Kanai Y, Endou H: Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs. J Pharmacol Exp Ther. 2000 Sep;294(3):844-9. Pubmed
          2. Takeda, M. et al. Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther 300, 918- 924 (2002).Pubmed

          3. Solute carrier family 22 member 7

          Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha- ketoglutarate

          UniProt ID: Q9Y694 Link_out
          Gene: SLC22A7 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. Pubmed

          4. Solute carrier family 22 member 8

          Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone- 3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA)

          UniProt ID: Q8TCC7 Link_out
          Gene: SLC22A8 Link_out
          Protein Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. Pubmed

          5. Solute carrier family 22 member 11

          Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds

          UniProt ID: Q9NSA0 Link_out
          Gene: SLC22A11 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          SNPs: SNPJam Report Link_out

          References:
          1. Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. Pubmed

          6. Sodium/nucleoside cotransporter 1

          UniProt ID: O00337 Link_out

          References:
          1. Cano-Soldado P, Lorrayoz IM, Molina-Arcas M, Casado FJ, Martinez-Picado J, Lostao MP, Pastor-Anglada M: Interaction of nucleoside inhibitors of HIV-1 reverse transcriptase with the concentrative nucleoside transporter-1 (SLC28A1). Antivir Ther. 2004 Dec;9(6):993-1002. Pubmed

          7. Equilibrative nucleoside transporter 2

          UniProt ID: Q14542 Link_out

          References:
          1. Yao SY, Ng AM, Sundaram M, Cass CE, Baldwin SA, Young JD: Transport of antiviral 3’-deoxy-nucleoside drugs by recombinant human and rat equilibrative, nitrobenzylthioinosine (NBMPR)-insensitive (ENT2) nucleoside transporter proteins produced in Xenopus oocytes. Mol Membr Biol. 2001 Apr-Jun;18(2):161-7. 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 February 22, 2013 18:12