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Identification
Name Stavudine
Accession Number DB00649 (APRD00440)
Type small molecule
Groups approved
Description

A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • 2',3'-Didehydro-3'-deoxythimidine
  • 3'-Deoxy-2'-thymidinene
  • Estavudina [INN-Spanish]
  • Sanilvudine
  • stavudine
  • Stavudine [Usan:Ban:Inn]
  • Stavudinum [INN-Latin]
  • STV
Brand names
  • Zerit
  • Zerit XR
  • Zerut XR
Brand name mixtures Not Available
Categories
  • Anti-HIV Agents
  • Antimetabolites
  • Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
  • Reverse Transcriptase Inhibitors
CAS number 3056-17-5
Weight Average: 224.2133
Monoisotopic: 224.079706882
Chemical Formula C10H12N2O4
InChI Key InChIKey=XNKLLVCARDGLGL-JGVFFNPUSA-N
InChI
InChI=1S/C10H12N2O4/c1-6-4-12(10(15)11-9(6)14)8-3-2-7(5-13)16-8/h2-4,7-8,13H,5H2,1H3,(H,11,14,15)/t7-,8+/m0/s1
Plain Text
IUPAC Name
1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
SMILES
CC1=CN([C@@H]2O[C@H](CO)C=C2)C(=O)NC1=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Pyrimidines and Derivatives
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Ethers
  • Alcohols and Polyols
  • Pyrimidines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Cyanamides
Pharmacology
Indication For the treatment of human immunovirus (HIV) infections.
Pharmacodynamics Stavudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Stavudine 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 Stavudine 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 Following oral administration, stavudine is rapidly absorbed (bioavailability is 68-104%).
Volume of distribution
  • 46 ± 21 L
Protein binding Negligible
Metabolism

Phosphorylated intracellularly to stavudine triphosphate, the active substrate for HIV-reverse transcriptase.
Route of elimination Not Available
Half life 0.8-1.5 hours (in adults)
Clearance
  • Renal cl=272 mL/min [Healthy subjects receiving 80 mg PO]
  • 594 +/- 164 mL/min [HIV-infected adult and pediatric patients following 1-hour IV infusion]
  • 9.75 +/- 3.76 mL/min/kg [HIV- Exposed or -Infected Pediatric Patients(Age 5 weeks – 15 years) following 1-hour IV infusion]
Toxicity Side effects include peripheral neuropathy tingling, burning, numbness, or pain in the hands or feet), fatal lactic acidosis has been reported in patients treated with stavudine (ZERIT) in combination with other antiretroviral agents, severe liver enlargement, inflammation (pain and swelling) of the liver, and liver failure.
Affected organisms
  • Human Immunodeficiency Virus
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb co
  • Aurobindo pharma ltd
  • Hetero drugs ltd
  • Matrix laboratories ltd
  • Mylan pharmaceuticals inc
  • Bristol myers squibb co pharmaceutical research institute
  • Cipla ltd
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Prices
Unit description Cost Unit
Zerit 1 mg/ml Solution 200ml Bottle 88.11 USD bottle
Zerit 40 mg capsule 7.75 USD capsule
Zerit 30 mg capsule 7.61 USD capsule
Zerit 20 mg capsule 7.17 USD capsule
Stavudine 40 mg capsule 6.99 USD capsule
Zerit 15 mg capsule 6.89 USD capsule
Stavudine 30 mg capsule 6.72 USD capsule
Stavudine 20 mg capsule 6.33 USD capsule
Stavudine 15 mg capsule 6.08 USD capsule
Patents
Country Patent Number Approved Expires
United States 7135465 2003-08-18 2023-08-18
Properties
State solid
Melting point 159 - 160 oC
Experimental Properties
Property Value Source
water solubility 5-10 g/100 mL at 21 oC PhysProp
logP -0.8 PhysProp
Predicted Properties
Property Value Source
water solubility 4.05e+01 g/l ALOGPS
logP -0.73 ALOGPS
logP -0.23 ChemAxon Molconvert
logS -0.74 ALOGPS
pKa 14.63 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 78.87 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 55.32 ChemAxon Molconvert
polarizability 21.33 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00445 Link_out
KEGG Compound C07312 Link_out
PubChem Compound 18283 Link_out
PubChem Substance 46506943 Link_out
ChemSpider 17270 Link_out
BindingDB 50013111 Link_out
Therapeutic Targets Database DAP000172 Link_out
PharmGKB PA451494 Link_out
Drug Product Database 2216094 Link_out
RxList http://www.rxlist.com/cgi/generic/stavudin.htm Link_out
Drugs.com http://www.drugs.com/cdi/stavudine.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/zer1496.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Stavudine Link_out
ATC Codes
  • J05AF04
AHFS Codes
  • 08:18.08.20
PDB Entries Not Available
FDA label show (288.5 KB)
MSDS show (36.8 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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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
  3. Goldschmidt V, Marquet R: Primer unblocking by HIV-1 reverse transcriptase and resistance to nucleoside RT inhibitors (NRTIs). Int J Biochem Cell Biol. 2004 Sep;36(9):1687-705. Pubmed
Transporters

1. Solute carrier family 22 member 6

Actions: substrate
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
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:41

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.