STAVUDINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H12N2O4
Molecular Weight	224.2133
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CC1=CN([C@@H]2O[C@H](CO)C=C2)C(=O)NC1=O

InChI

InChIKey=XNKLLVCARDGLGL-JGVFFNPUSA-N

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

HIDE SMILES / InChI

Molecular Formula	C10H12N2O4
Molecular Weight	224.2133
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

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. 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. Stavudine is used for the treatment of human immunovirus (HIV) infections. Stavudine is sold under the brand name Zerit among others.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus 1 34	Inhibitor 8,504		1.9 µM [IC50]
Human immunodeficiency virus type 1 reverse transcriptase 70	Inhibitor 8,504		0.0083 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 156	Primary		Approved 8,583	Zerit

C_max

Value	Dose	Co-administered	Analyte	Population
228 ng/mL	100 mg 1 times / day steady-state, oral		STAVUDINE plasma	Homo sapiens
536 ng/mL	40 mg 2 times / day steady-state, oral		STAVUDINE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
1966 ng × h/mL	100 mg 1 times / day steady-state, oral		STAVUDINE plasma	Homo sapiens
2568 ng × h/mL	40 mg 2 times / day steady-state, oral		STAVUDINE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
100%	100 mg 1 times / day steady-state, oral		STAVUDINE plasma	Homo sapiens
100%	40 mg 2 times / day steady-state, oral		STAVUDINE plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
40 mg 2 times / day multiple, oral Recommended	unhealthy, 36.5	Other AEs: Abdominal pain, Asthenia...
40 mg 2 times / day multiple, oral Recommended	unhealthy, adult	Other AEs: Headache, Diarrhea...
40 mg 2 times / day multiple, oral Recommended	unhealthy, adult	Other AEs: Nausea, Diarrhea...
40 mg 2 times / day multiple, oral Recommended	unhealthy, adult	Other AEs: Nausea, Diarrhea...

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AEs

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AE	Significance	Dose	Population
Rhinitis	11%	40 mg 2 times / day multiple, oral Recommended	unhealthy, 36.5
Dyspepsia	12%	40 mg 2 times / day multiple, oral Recommended	unhealthy, 36.5
Paresthesia	12%	40 mg 2 times / day multiple, oral Recommended	unhealthy, 36.5
Vomiting	12%	40 mg 2 times / day multiple, oral Recommended	unhealthy, 36.5
Depressive disorders	13%	40 mg 2 times / day multiple, oral Recommended	unhealthy, 36.5

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,946 inhibitor 2,252	substrate 1,193 inhibitor 2,438	substrate 1,388 inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1,057 CYP2B6 926 CYP1A2 2,153 CYP2A6 879 CYP2C19 2,057 CYP2E1 1,060 BSEP 550 MRP2 499 MRP3 246 MRP4 290	CYP1A2 1,197 CYP2C19 1,119 BCRP 697 P-gp 2,052	P-gp 301

Drug as perpetrator

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Target	Modality	Activity
CYP1A2 2,333	inhibitor 4,027	no [IC50 >10 uM]
CYP2A6 911	inhibitor 4,027	no [IC50 >10 uM]
CYP2C19 2,141	inhibitor 4,027	no [IC50 >10 uM]
CYP2C9 2,497	inhibitor 4,027	no [IC50 >10 uM]
CYP2D6 2,546	inhibitor 4,027	no [IC50 >10 uM]

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Drug as victim

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Target	Modality	Activity
CYP1A2 1,197	substrate 4,014	no
CYP2C19 1,119	substrate 4,014	no
CYP2C9 1,193	substrate 4,014	no
CYP2D6 1,388	substrate 4,014	no
CYP3A4 1,946	substrate 4,014	no

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63581	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63581
ChemicalBook	CB4450928	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4450928
eMolecules	536927	https://www.emolecules.com/cgi-bin/more?vid=536927
eMolecules	739264	https://www.emolecules.com/cgi-bin/more?vid=739264
MolPort	MolPort-002-507-283	https://www.molport.com/shop/molecule-link/MolPort-002-507-283

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PubMed

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Title	Date	PubMed
Anti-HIV antiviral activity of stavudine in a thymidine kinase-deficient cellular line.	1998	10682138
[Conjugates of 2',3'-didehydro-3'-deoxythymidine with thymogen. Synthesis and anti-HIV activity].	1999 Jul	10563202
A novel genotype encoding a single amino acid insertion and five other substitutions between residues 64 and 74 of the HIV-1 reverse transcriptase confers high-level cross-resistance to nucleoside reverse transcriptase inhibitors. Abacavir CNA2007 International Study Group.	1999 Oct 1	10843527
Once-daily administration of didanosine in combination with stavudine in antiretroviral-naive patients. The STADI Group.	1999 Sep 1	10534154
Activities of masked 2',3'-dideoxynucleoside monophosphate derivatives against human immunodeficiency virus in resting macrophages.	2000 Jan	10602742

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Patents

Sample Use Guides

In Vivo Use Guide

Adults: The recommended dose based on body weight is as follows: 40 mg twice daily for patients ≥60 kg. 30 mg twice daily for patients <60 kg.

Route of Administration: Oral

In Vitro Use Guide

The concentration of Stavudine necessary to inhibit HIV-1 replication by 50% (EC50) ranged from 0.009 to 4 uM

Substance Class	Chemical
Record UNII	BO9LE4QFZF
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SANILVUDINE

Preferred Name

English

STAVUDINE

Official Name

English

STAVUDINE [WHO-IP]

Common Name

English

STAVUDINE [MI]

Common Name

English

STAVUDINE [USAN]

Common Name

English

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Classification Tree

Code System

Code

Established Pharmacologic Class

NDF-RT

N0000175462

Reverse Transcriptase Inhibitors

NDF-RT

N0000009947

Analogs/Derivatives

NDF-RT

N0000175459

Antiretrovirals

WHO-ESSENTIAL MEDICINES LIST

6.4.2.3 (LAM/NEV/STA)

Reverse Transcriptase Inhibitor

NCI_THESAURUS

C97452

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Code System

Code

Type

Description

NSC

759897

PRIMARY

NCI_THESAURUS

C1428

PRIMARY

RXCUI

59763

PRIMARY

RxNorm

NSC

163661

PRIMARY

WIKIPEDIA

STAVUDINE

PRIMARY

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Related Record

Type

Details


					BO9LE4QFZF

STAVUDINE

EXCRETED UNCHANGED

Interaction Type:

AMOUNT EXCRETED

Qualification:

URINE

Amount:

67 % (average)
of dose


					A3Z87NSO0U

HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 POLYMERASE

TARGET -> INHIBITOR

Amount:


					859A956UY8

HUMAN IMMUNODEFICIENCY VIRUS TYPE 1

TARGET ORGANISM->INHIBITOR

Amount:

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Related Record

Type

Details


					KX2B81V402

N-ACETYL-L-CYSTEINE 2-DEOXY-3-THIO-D-ERYTHRO-PENTONIC ACID .GAMMA.-LACTONE THIOETHER

METABOLITE -> PARENT

Interaction Type:

MINOR

Qualification:

URINE

Amount:


					QR26YLT7LT

THYMINE

METABOLITE -> PARENT

Amount:


					1ZP0VJ751G

STAVUDINE TRIPHOSPHATE

METABOLITE ACTIVE -> PARENT

Comments:

The in vitro MIC (50% inhibitory concentration [IC50]) of d4T-TP against HIV-1 has been found to be between 0.009 and 6 ?M, depending on the phenotypic and genotypic resistance to nucleoside reverse transcriptase inhibitors.

Interaction Type:

MAJOR

Amount:

[0.009 to 6] MICROMOLAR (average)


					X4PT8NAI8E

STAVUDINE GLUCURONIDE

METABOLITE -> PARENT

Interaction Type:

MINOR

Qualification:

URINE

Amount:

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Related Record

Type

Details


					059QF0KO0R

WATER

IMPURITY -> PARENT

Comments:

Water (2.5.12): maximum 0.5 per cent, determined on 0.500 g.

Qualification:

EP

Amount:

[<0.5] % (limits)


					E37QXU5N74

THYMIDINE, 2',3'-DIDEHYDRO-3'-DEOXY-5'-O-(1,2,5-TRIDEOXY-1-(3,4-DIHYDRO-5-METHYL-2,4-DIOXO-1(2H)-PYRIMIDINYL)-.BETA.-D-THREO-PENTOFURANOS-5-YL)-

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

[<0.2] PERCENT PEAK AREA (limits)


					5Y0U269FPI

1-(4-(HYDROXYMETHYL)-2-OXO-2,5-DIHYDROFURAN-3-YL)-5-METHYLPYRIMIDINE-2,4(1H,3H)-DIONE

IMPURITY -> PARENT

Comments:

Amount Not Specified

Qualification:

INTERNATIONAL PHARMACOPEIA

Amount:


					J69N0KNC59

STAVUDINE.ALPHA.-ANOMER

IMPURITY -> PARENT

Comments:

Amount Not Specified

Qualification:

INTERNATIONAL PHARMACOPEIA

Amount:


					19TWX5TRJ4

3',5'-ANHYDROTHYMIDINE

IMPURITY -> PARENT

Comments:

Amount Not Specified

Qualification:

INTERNATIONAL PHARMACOPEIA

Amount:

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Related Record

Type

Details


					BO9LE4QFZF

STAVUDINE

ACTIVE MOIETY

Amount:

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Name	Property Type	Amount	Parameters
Tmax	PHARMACOKINETIC	0.5 hours (average)	ORAL ADMINISTRATION

Biological Half-life	PHARMACOKINETIC	2.3 hours (average)	ORAL ADMINISTRATION

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

F_unbound

Drug as perpetrator