Stavudine

Identification

Summary

Stavudine is a dideoxynucleoside used in the treatment of HIV infection.

Brand Names
Zerit
Generic Name
Stavudine
DrugBank Accession Number
DB00649
Background

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

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 224.2133
Monoisotopic: 224.079706882
Chemical Formula
C10H12N2O4
Synonyms
  • 1-(2,3-Dideoxy-beta-D-glycero-pent-2-enofuranosyl)thymine
  • 2',3'-Didehydro-3'-deoxythimidine
  • 3'-Deoxy-2'-thymidinene
  • Estavudina
  • Sanilvudine
  • Stavudin
  • Stavudine
  • Stavudinum
  • STV
External IDs
  • BMY 27857
  • BMY-27857
  • d4T
  • NSC-163661

Pharmacology

Indication

For the treatment of human immunovirus (HIV) infections.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to manageHiv infection••••••••••••
Contraindications & Blackbox Warnings
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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.

TargetActionsOrganism
AReverse transcriptase/RNaseH
inhibitor
Human immunodeficiency virus 1
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]
Adverse Effects
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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.

Pathways
PathwayCategory
Stavudine Action PathwayDrug action
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcetazolamideThe excretion of Stavudine can be decreased when combined with Acetazolamide.
AcetophenazineStavudine may increase the neurotoxic activities of Acetophenazine.
Acetylsalicylic acidThe excretion of Stavudine can be decreased when combined with Acetylsalicylic acid.
AcipimoxThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Stavudine is combined with Acipimox.
AcyclovirThe excretion of Stavudine can be decreased when combined with Acyclovir.
Food Interactions
  • Avoid alcohol. Ingesting alcohol while taking stavudine may increase the risk of liver damage and pancreatitis.
  • Take with or without food.

Products

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Product Images
International/Other Brands
Actastav (Actavis) / Ai Fu Ding (Wujing Medicine) / Avostav (Ranbaxy Laboratories) / Estavudox (Biotoscana) / Exvihr (Biogen) / Flamistav (Flamingo Pharmacueticals) / Landstav (Landsteiner) / Lion (Filaxis) / Mai Si Ting (Meijisi Pharmaceutical) / S.T.V. (Ivax) / Sazi (NEGPF) / Stadine (Stadine) / Stag (Hetero) / Stamar (LKM) / Stavex (Aurobindo) / Stavir (Cipla) / Stavubergen (Paylos) / Zerit XR (Bristol-Myers Squibb)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ZeritPowder, for solution200 mgOralBristol Myers Squibb Pharma Eeig2016-09-082020-10-13EU flag
ZeritCapsule, gelatin coated30 mg/1OralPhysicians Total Care, Inc.1994-06-242010-06-30US flag
ZeritCapsule30 mgOralBristol Myers Squibb Pharma Eeig2016-09-082020-10-13EU flag
ZeritCapsule, gelatin coated40 mg/1OralState of Florida DOH Central Pharmacy2009-07-01Not applicableUS flag
ZeritCapsule20 mgOralBristol Myers Squibb Pharma Eeig2016-09-082020-10-13EU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
StavudineCapsule20 mg/1OralRising Pharmaceuticals, Inc.2008-12-29Not applicableUS flag
StavudineCapsule40 mg/1OralState of Florida DOH Central Pharmacy2009-07-01Not applicableUS flag
StavudineCapsule30 mg/1OralAurobindo Pharma Limited2008-12-29Not applicableUS flag
StavudineCapsule30 mg/1OralCamber Pharmaceuticals2008-12-29Not applicableUS flag
StavudineFor solution1 mg/1mLOralCipla Ltd.2009-03-20Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
จีพีโอเวียร์ เอส 30Stavudine (30 MG) + Lamivudine (150 MG) + Nevirapine (200 MG)องค์การเภสัชกรรม2003-11-14Not applicableThailand flag

Categories

ATC Codes
J05AF04 — StavudineJ05AR07 — Stavudine, lamivudine and nevirapine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Nucleoside and nucleotide analogues
Sub Class
Not Available
Direct Parent
Nucleoside and nucleotide analogues
Alternative Parents
Pyrimidones / Hydropyrimidines / Vinylogous amides / Heteroaromatic compounds / Dihydrofurans / Ureas / Lactams / Oxacyclic compounds / Azacyclic compounds / Primary alcohols
show 4 more
Substituents
Alcohol / Aromatic heteromonocyclic compound / Azacycle / Dihydrofuran / Heteroaromatic compound / Hydrocarbon derivative / Hydropyrimidine / Lactam / Organic nitrogen compound / Organic oxide
show 11 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organic molecular entity, dihydrofuran, nucleoside analogue (CHEBI:63581)
Affected organisms
  • Human Immunodeficiency Virus

Chemical Identifiers

UNII
BO9LE4QFZF
CAS number
3056-17-5
InChI Key
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[C@H](CO)C=C2)C(=O)NC1=O

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 References
Not Available
Human Metabolome Database
HMDB0014787
KEGG Drug
D00445
KEGG Compound
C07312
PubChem Compound
18283
PubChem Substance
46506943
ChemSpider
17270
BindingDB
50013111
RxNav
59763
ChEBI
63581
ChEMBL
CHEMBL991
ZINC
ZINC000000137884
Therapeutic Targets Database
DAP000172
PharmGKB
PA451494
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Stavudine
FDA label
Download (289 KB)
MSDS
Download (36.8 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

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
  • A-S Medication Solutions LLC
  • Aurobindo Pharma Ltd.
  • Bristol-Myers Squibb Co.
  • Camber Pharmaceuticals Inc.
  • Cipla Ltd.
  • DAVA Pharmaceuticals
  • Dept Health Central Pharmacy
  • Dispensing Solutions
  • E.R. Squibb and Sons LLC
  • Greenstone LLC
  • Hetero Drugs Ltd.
  • Kaiser Foundation Hospital
  • Matrix Laboratories Ltd.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Nucare Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Remedy Repack
  • Tya Pharmaceuticals
Dosage Forms
FormRouteStrength
TabletOral
Capsule, coatedOral40 mg
Tablet, film coatedOral
Capsule, coatedOral30 mg
Tablet
CapsuleOral15 mg/1
CapsuleOral20 mg/1
CapsuleOral30 mg/1
CapsuleOral40 mg/1
For solutionOral1 mg/1mL
Powder, for solutionOral1 mg/1mL
SolutionOral1 mg/1mL
Capsule, gelatin coatedOral15 mg/1
Capsule, gelatin coatedOral20 mg/1
Capsule, gelatin coatedOral30 mg/1
Capsule, gelatin coatedOral40 mg/1
Powder, for solutionOral1 mg / mL
Powder, for solutionOral200 MG
CapsuleOral15 mg
CapsuleOral20 mg
CapsuleOral40 mg
Capsule, coatedOral15 mg
Capsule, coatedOral20 mg
Powder, for solutionOral100 mg
CapsuleOral30 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)Region
US7135465Yes2006-11-142023-08-18US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)159-160 °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 RuleNoChemaxon
MDDR-like RuleNoChemaxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-004i-9710000000-ec1b8accee7609d895af
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0059-6910000000-ee6276bb4983704d536c
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0290000000-12b63ee41b4c51c88333
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-053r-9300000000-ac384902323df1ff4053
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0f6x-9400000000-c72ca17c2cd4c5d99043
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a5c-9600000000-73308caa87c5d7c1fac1
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9600000000-f1ede0bee7340eda0bbd
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-158.3054758
predicted
DarkChem Lite v0.1.0
[M-H]-158.46
predicted
DarkChem Lite v0.1.0
[M-H]-157.8131758
predicted
DarkChem Lite v0.1.0
[M-H]-150.8308
predicted
DeepCCS 1.0 (2019)
[M+H]+159.9202758
predicted
DarkChem Lite v0.1.0
[M+H]+161.3
predicted
DarkChem Lite v0.1.0
[M+H]+158.5818758
predicted
DarkChem Lite v0.1.0
[M+H]+153.22636
predicted
DeepCCS 1.0 (2019)
[M+Na]+159.2775758
predicted
DarkChem Lite v0.1.0
[M+Na]+158.94
predicted
DarkChem Lite v0.1.0
[M+Na]+158.5629758
predicted
DarkChem Lite v0.1.0
[M+Na]+159.13899
predicted
DeepCCS 1.0 (2019)

Targets

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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
Uniprot Name
Reverse transcriptase/RNaseH
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. [Article]
  2. De Clercq E: Emerging anti-HIV drugs. Expert Opin Emerg Drugs. 2005 May;10(2):241-73. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
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 colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Bocedi A, Notaril S, Narciso P, Bolli A, Fasano M, Ascenzi P: Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. [Article]
  2. Bocedi A, Notari S, Menegatti E, Fanali G, Fasano M, Ascenzi P: Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin. FEBS J. 2005 Dec;272(24):6287-96. [Article]

Transporters

Kind
Protein
Organism
Humans
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 ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
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. [Article]
Kind
Protein
Organism
Humans
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)....
Gene Name
SLC28A1
Uniprot ID
O00337
Uniprot Name
Sodium/nucleoside cotransporter 1
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. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54