Identification

Name
Stavudine
Accession Number
DB00649  (APRD00440)
Type
Small Molecule
Groups
Approved, 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 IDs
BMY 27857 / d4T / NSC-163661
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ZeritCapsule, gelatin coated40 mg/1OralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
ZeritPowder, for solution1 mgOralBristol Myers SquibbNot applicableNot applicableCanada
ZeritCapsule, gelatin coated40 mg/1OralE.R. Squibb & Sons, L.L.C.2017-06-13Not applicableUs
ZeritCapsule40 mgOralBristol Myers Squibb Pharma Eeig1996-05-08Not applicableEu
ZeritCapsule, gelatin coated15 mg/1OralE.R. Squibb & Sons, L.L.C.2017-06-13Not applicableUs
ZeritCapsule30 mgOralBristol Myers Squibb Pharma Eeig1996-05-08Not applicableEu
ZeritCapsule, gelatin coated20 mg/1OralPhysicians Total Care, Inc.1994-06-242001-06-30Us
ZeritCapsule15 mgOralBristol Myers Squibb Pharma Eeig1996-05-08Not applicableEu
ZeritCapsule, gelatin coated30 mg/1OralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
ZeritCapsule40 mgOralBristol Myers Squibb Pharma Eeig1996-05-08Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
StavudineCapsule15 mg/1OralMylan Pharmaceuticals2011-08-242018-05-31Us
StavudineCapsule20 mg/1OralCitron Pharma LLC2008-12-29Not applicableUs
StavudineCapsule40 mg/1OralCamber Pharmaceuticals2008-12-29Not applicableUs
StavudineCapsule40 mg/1OralRemedy Repack2010-03-102012-08-23Us
StavudineCapsule15 mg/1OralCamber Pharmaceuticals2008-12-29Not applicableUs
StavudineCapsule20 mg/1OralAurobindo Pharma2008-12-29Not applicableUs
StavudineCapsule40 mg/1OralRising Pharmaceuticals2008-12-29Not applicableUs
StavudineCapsule20 mg/1OralState of Florida DOH Central Pharmacy2013-01-01Not applicableUs
StavudineCapsule15 mg/1OralRising Pharmaceuticals2008-12-29Not applicableUs
StavudineCapsule20 mg/1OralGreenstone, Llc2008-12-292013-03-31Us
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)
Categories
UNII
BO9LE4QFZF
CAS number
3056-17-5
Weight
Average: 224.2133
Monoisotopic: 224.079706882
Chemical Formula
C10H12N2O4
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

Pharmacology

Indication

For the treatment of human immunovirus (HIV) infections.

Associated Conditions
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]
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
PathwayCategory
Stavudine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AmoxicillinThe excretion of Stavudine can be decreased when combined with Amoxicillin.
BaclofenThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Stavudine is combined with Baclofen.
BumetanideThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Stavudine is combined with Bumetanide.
CeftazidimeThe excretion of Stavudine can be decreased when combined with Ceftazidime.
CladribineThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Cladribine is combined with Stavudine.
DaptomycinThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Daptomycin is combined with Stavudine.
DidanosineThe risk or severity of adverse effects can be increased when Stavudine is combined with Didanosine.
DiflunisalThe excretion of Stavudine can be decreased when combined with Diflunisal.
DoxorubicinThe therapeutic efficacy of Stavudine can be decreased when used in combination with Doxorubicin.
DoxycyclineThe excretion of Stavudine can be decreased when combined with Doxycycline.
Food Interactions
Not 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 References
Not Available
External Links
Human Metabolome Database
HMDB0014787
KEGG Drug
D00445
KEGG Compound
C07312
PubChem Compound
18283
PubChem Substance
46506943
ChemSpider
17270
BindingDB
50013111
ChEBI
63581
ChEMBL
CHEMBL991
Therapeutic Targets Database
DAP000172
PharmGKB
PA451494
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Stavudine
ATC Codes
J05AF04 — StavudineJ05AR07 — Stavudine, lamivudine and nevirapine
AHFS Codes
  • 08:18.08.20 — Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
FDA label
Download (289 KB)
MSDS
Download (36.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections10
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Pregnancy1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis1
1TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
1, 2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections34
2SuspendedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
2Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections3
2WithdrawnTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2, 3CompletedTreatmentAcidosis, Respiratory1
2, 3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentAIDS-Associated Nephropathy / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentAIDS-Related Dementia Complex / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV)1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections16
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
3SuspendedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections2
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
4CompletedDiagnosticAIDS-Related Opportunistic Infections / Human Immunodeficiency Virus (HIV) Infections1
4CompletedDiagnosticCardiovascular Disease (CVD) / HIV-Associated Lipodystrophy Syndrome1
4CompletedDiagnosticHuman Immunodeficiency Virus (HIV) Infections / Lipodystrophies1
4CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHemophilia A / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV)2
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections3
4CompletedTreatmentHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
4TerminatedTreatmentMetabolic Complications / Mitochondrial Toxicity1
4Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV)1
4Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections2
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections24
Not AvailableRecruitingNot AvailableHuman Immunodeficiency Virus (HIV) Infections1

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
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
Powder, for solutionOral200 mg
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)
US7135465Yes2003-08-182023-08-18Us

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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Pyrimidone / Hydropyrimidine / Pyrimidine / Dihydrofuran / Vinylogous amide / Heteroaromatic compound / Lactam / Urea / Organoheterocyclic compound / Azacycle
show 11 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organic molecular entity, dihydrofuran, nucleoside analogue (CHEBI:63581)

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
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. [PubMed:8861550]

Carriers

Kind
Protein
Organism
Human
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. [PubMed:15814459]
  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. [PubMed:16336266]

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 ...
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. [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)....
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. [PubMed:15651758]

Drug created on June 13, 2005 07:24 / Updated on September 21, 2018 20:42