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Identification
NameStavudine
Accession NumberDB00649  (APRD00440)
TypeSmall Molecule
GroupsApproved, Investigational
Description

A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV. [PubChem]

Structure
Thumb
Synonyms
1-(2,3-Dideoxy-beta-D-glycero-pent-2-enofuranosyl)thymine
2',3'-Didehydro-3'-deoxythimidine
3'-Deoxy-2'-thymidinene
d4T
Estavudina
Sanilvudine
Stavudin
Stavudine
Stavudinum
STV
External Identifiers
  • BMY 27857
  • d4T
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Zeritcapsule, gelatin coated15 mg/1oralE.R. Squibb & Sons, L.L.C.1994-06-24Not applicableUs
Zeritcapsule, gelatin coated40 mg/1oralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
Zeritcapsule, gelatin coated30 mg/1oralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
Zeritcapsule, gelatin coated20 mg/1oralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
Zeritpowder for solution1 mgoralBristol Myers Squibb CanadaNot applicableNot applicableCanada
Zeritpowder, for solution1 mg/mLoralE.R. Squibb & Sons, L.L.C.1996-09-06Not applicableUs
Zeritcapsule, gelatin coated40 mg/1oralE.R. Squibb & Sons, L.L.C.1994-06-24Not applicableUs
Zeritcapsule, gelatin coated30 mg/1oralE.R. Squibb & Sons, L.L.C.1994-06-24Not applicableUs
Zeritcapsule, gelatin coated20 mg/1oralE.R. Squibb & Sons, L.L.C.1994-06-24Not applicableUs
Zerit - Cap 15mgcapsule15 mgoralBristol Myers Squibb Canada1996-07-30Not applicableCanada
Zerit - Cap 20mgcapsule20 mgoralBristol Myers Squibb Canada1996-07-30Not applicableCanada
Zerit - Cap 30mgcapsule30 mgoralBristol Myers Squibb Canada1996-07-30Not applicableCanada
Zerit - Cap 40mgcapsule40 mgoralBristol Myers Squibb Canada1996-07-30Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Stavudinecapsule40 mg/1oralKAISER FOUNDATION HOSPITALS2010-01-27Not applicableUs
Stavudinepowder, for solution1 mg/mLoralAurobindo Pharma Limited2008-12-292016-02-29Us
Stavudinecapsule40 mg/1oralAurobindo Pharma Limited2008-12-29Not applicableUs
Stavudinecapsule40 mg/1oralCamber Pharmaceuticals, Inc.2008-12-29Not applicableUs
Stavudinecapsule30 mg/1oralAurobindo Pharma Limited2008-12-29Not applicableUs
Stavudinecapsule30 mg/1oralCamber Pharmaceuticals, Inc.2008-12-29Not applicableUs
Stavudinesolution1 mg/mLoralBoca Pharmacal, LLC2012-08-17Not applicableUs
Stavudinecapsule20 mg/1oralCamber Pharmaceuticals, Inc.2008-12-29Not applicableUs
Stavudinecapsule20 mg/1oralState of Florida DOH Central Pharmacy2013-01-01Not applicableUs
Stavudinecapsule15 mg/1oralCamber Pharmaceuticals, Inc.2008-12-29Not applicableUs
Stavudinecapsule40 mg/1oralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
Stavudinecapsule40 mg/1oralMylan Pharmaceuticals Inc.2011-08-24Not applicableUs
Stavudinecapsule40 mg/1oralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
Stavudinecapsule30 mg/1oralMylan Pharmaceuticals Inc.2011-08-24Not applicableUs
Stavudinefor solution1 mg/mLoralCipla Ltd.2009-03-20Not applicableUs
Stavudinecapsule40 mg/1oralREMEDYREPACK INC.2010-11-11Not applicableUs
Stavudinecapsule20 mg/1oralMylan Pharmaceuticals Inc.2011-08-24Not applicableUs
Stavudinecapsule20 mg/1oralAurobindo Pharma Limited2008-12-29Not applicableUs
Stavudinepowder, for solution1 mg/mLoralEdenbridge Pharmaceuticals, LLC2012-04-01Not applicableUs
Stavudinecapsule15 mg/1oralMylan Pharmaceuticals Inc.2011-08-24Not applicableUs
Stavudinecapsule15 mg/1oralAurobindo Pharma Limited2008-12-29Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ActastavActavis
Ai Fu DingWujing Medicine
AvostavRanbaxy Laboratories
EstavudoxBiotoscana
ExvihrBiogen
FlamistavFlamingo Pharmacueticals
LandstavLandsteiner
LionFilaxis
Mai Si TingMeijisi Pharmaceutical
S.T.V.Ivax
SaziNEGPF
StadineStadine
StagHetero
StamarLKM
StavexAurobindo
StavirCipla
StavubergenPaylos
Zerit XRBristol-Myers Squibb
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIBO9LE4QFZF
CAS number3056-17-5
WeightAverage: 224.2133
Monoisotopic: 224.079706882
Chemical FormulaC10H12N2O4
InChI KeyInChIKey=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
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[[email protected]](CO)C=C2)C(=O)NC1=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as nucleoside and nucleotide analogues. These are analogues of nucleosides and nucleotides. These include phosphonated nucleosides, C-glycosylated nucleoside bases, analogues where the sugar unit is a pyranose, and carbocyclic nucleosides, among others.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassNucleoside and nucleotide analogues
Sub ClassNot Available
Direct ParentNucleoside and nucleotide analogues
Alternative Parents
Substituents
  • Pyrimidone
  • Pyrimidine
  • Hydropyrimidine
  • Heteroaromatic compound
  • Vinylogous amide
  • Dihydrofuran
  • Urea
  • Lactam
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of human immunovirus (HIV) infections.
PharmacodynamicsStavudine 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 actionStavudine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.
Related Articles
AbsorptionFollowing oral administration, stavudine is rapidly absorbed (bioavailability is 68-104%).
Volume of distribution
  • 46 ± 21 L
Protein bindingNegligible
Metabolism

Phosphorylated intracellularly to stavudine triphosphate, the active substrate for HIV-reverse transcriptase.

Route of eliminationNot Available
Half life0.8-1.5 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]
ToxicitySide 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
PathwayCategorySMPDB ID
Stavudine Action PathwayDrug actionSMP00745
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9889
Blood Brain Barrier+0.9381
Caco-2 permeable-0.8958
P-glycoprotein substrateNon-substrate0.7949
P-glycoprotein inhibitor INon-inhibitor0.9073
P-glycoprotein inhibitor IINon-inhibitor0.7979
Renal organic cation transporterNon-inhibitor0.9226
CYP450 2C9 substrateNon-substrate0.6707
CYP450 2D6 substrateNon-substrate0.8872
CYP450 3A4 substrateNon-substrate0.6011
CYP450 1A2 substrateNon-inhibitor0.9336
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9269
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9445
Ames testNon AMES toxic0.7275
CarcinogenicityNon-carcinogens0.8131
BiodegradationNot ready biodegradable0.6132
Rat acute toxicity1.7802 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9413
hERG inhibition (predictor II)Non-inhibitor0.9375
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
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
FormRouteStrength
Capsuleoral15 mg/1
Capsuleoral20 mg/1
Capsuleoral30 mg/1
Capsuleoral40 mg/1
For solutionoral1 mg/mL
Solutionoral1 mg/mL
Capsule, gelatin coatedoral15 mg/1
Capsule, gelatin coatedoral20 mg/1
Capsule, gelatin coatedoral30 mg/1
Capsule, gelatin coatedoral40 mg/1
Powder for solutionoral1 mg
Powder, for solutionoral1 mg/mL
Capsuleoral15 mg
Capsuleoral20 mg
Capsuleoral30 mg
Capsuleoral40 mg
Prices
Unit descriptionCostUnit
Zerit 1 mg/ml Solution 200ml Bottle88.11USD bottle
Zerit 40 mg capsule7.75USD capsule
Zerit 30 mg capsule7.61USD capsule
Zerit 20 mg capsule7.17USD capsule
Stavudine 40 mg capsule6.99USD capsule
Zerit 15 mg capsule6.89USD capsule
Stavudine 30 mg capsule6.72USD capsule
Stavudine 20 mg capsule6.33USD capsule
Stavudine 15 mg capsule6.08USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7135465 Yes2003-08-182023-08-18Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point159-160 °CNot Available
water solubility5-10 g/100 mL at 21 °CNot Available
logP-0.72SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility40.5 mg/mLALOGPS
logP-0.73ALOGPS
logP-0.23ChemAxon
logS-0.74ALOGPS
pKa (Strongest Acidic)9.95ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area78.87 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity55.32 m3·mol-1ChemAxon
Polarizability21.33 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Purna Chandra Ray, Jagan Mohana Chary Tummanapalli, Seeta Ramanjaneyulu Gorantla, “Process for the Large Scale Production of Stavudine.” U.S. Patent US20080312428, issued December 18, 2008.

US20080312428
General ReferencesNot Available
External Links
ATC CodesJ05AF04J05AR07
AHFS Codes
  • 08:18.08.20
PDB EntriesNot Available
FDA labelDownload (289 KB)
MSDSDownload (36.8 KB)
Interactions
Drug Interactions
Drug
DidanosineThe risk or severity of adverse effects can be increased when Stavudine is combined with Didanosine.
DoxorubicinThe therapeutic efficacy of Stavudine can be decreased when used in combination with Doxorubicin.
HydroxyureaThe risk or severity of adverse effects can be increased when Hydroxyurea is combined with Stavudine.
RibavirinRibavirin may increase the hepatotoxic activities of Stavudine.
ZidovudineThe therapeutic efficacy of Stavudine can be decreased when used in combination with Zidovudine.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
yes
Actions
inhibitor
General Function:
Rna-dna hybrid ribonuclease activity
Specific Function:
Not Available
Gene Name:
pol
Uniprot ID:
Q72547
Molecular Weight:
65223.615 Da
References
  1. Lea AP, Faulds D: Stavudine: a review of its pharmacodynamic and pharmacokinetic properties and clinical potential in HIV infection. Drugs. 1996 May;51(5):846-64. [PubMed:8861550 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
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:10945832 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Pyrimidine- and adenine-specific:sodium symporter activity
Specific Function:
Sodium-dependent and pyrimidine-selective. Exhibits the transport characteristics of the nucleoside transport system cit or N2 subtype (N2/cit) (selective for pyrimidine nucleosides and adenosine). It also transports the antiviral pyrimidine nucleoside analogs 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC). It may be involved in the intestinal absorption and renal handling of ...
Gene Name:
SLC28A1
Uniprot ID:
O00337
Molecular Weight:
71583.18 Da
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:15651758 ]
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Drug created on June 13, 2005 07:24 / Updated on June 28, 2016 03:06