Details of the Drug

General Information of Drug (ID: DM6DEK9)

Drug Name

Stavudine

Synonyms

DdeThd; DdeTyd; Dideoxydidehydrothymidine; Estavudina; STV; Sanilvudine; Stavudinum; Zent; Zerit; Zerit Xr; Zerut XR; BMY 27857; BMY27857; D 1413; D 4T; BMY-27857; Bristol-Myers Brand of Stavudine; Bristol-Myers Squibb Brand of Stavudine; D 4T (nucleoside); Estavudina [INN-Spanish]; Sanilvudine (JAN); Stavudine, Monosodium Salt; Stavudinum [INN-Latin]; Zerit (TN); Zerit(TM); D4T & GM-CSF; D4TMBY-27857-3; Stavudine (USAN/INN); Stavudine [USAN:BAN:INN]; Stavudine [USAN:INN:BAN]; Thymine, 1-(2,3-dideoxy-beta-D-glycero-pent-2-enofuranosyl)-(7CI,8CI); 1-(2,3-Dideoxy-beta-D-glycero-2-pentenofuranosyl)thymine; 1-(2,3-Dideoxy-beta-D-glycero-pent-2-enofuranosyl)thymine; 1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4(1H,3H)-dione; 1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4-dione; 1-[5-(hydroxymethyl)-2,5-dihydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione & Colony-stimulating factor 2; 2',3' Didehydro 3' deoxythymidine; 2',3'-Anhydrothymidine; 2',3'-DIDEHYDRO-3'-DEOXYTHYMIDINE (DDI); 2',3'-Didehydro-2',3'-dideoxythmidine; 2',3'-Didehydro-3'-deoxythimidine; 2',3'-Didehydro-3'-deoxythymidine; 3'-Azido-3'-deoxythymidine & Granulocyte-macrophage colony-stimulating factor; 3'-Deoxy-2',3'-didehydrothymidine; 3'-Deoxy-2'-thymidinene; D4T

Indication

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[1]
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Therapeutic Class

Anti-HIV Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

224.21

Logarithm of the Partition Coefficient (xlogp)

-0.8

Rotatable Bond Count (rotbonds)

2

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

4

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [2]
Bioavailability: 82% of drug becomes completely available to its intended biological destination(s) [3]
Clearance: The renal clearance of drug is 272 mL/min []
Elimination: 39% of drug is excreted from urine in the unchanged form [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 0.8 - 1.5 hours (in adults) [4]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 5.94659 micromolar/kg/day [5]
Unbound Fraction: The unbound fraction of drug in plasma is 1% [4]
Vd: The volume of distribution (Vd) of drug is 46 +/- 21 L []
Water Solubility: The ability of drug to dissolve in water is measured as 83 mg/mL [2]

Chemical Identifiers

Formula: C10H12N2O4
IUPAC Name: 1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4-dione
Canonical SMILES: CC1=CN(C(=O)NC1=O)[C@H]2C=C[C@H](O2)CO
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
InChIKey: XNKLLVCARDGLGL-JGVFFNPUSA-N

Cross-matching ID

PubChem CID: 18283
ChEBI ID: CHEBI:63581
CAS Number: 3056-17-5
DrugBank ID: DB00649
TTD ID: D0Z8EX
ACDINA ID: D00639

Combinatorial Drugs (CBD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human immunodeficiency virus Reverse transcriptase (HIV RT)	TT84ETX	POL_HV1B1	Inhibitor	[6]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
60 kDa heat shock protein, mitochondrial (HSPD1)	OTTO1Y11	CH60_HUMAN	Gene/Protein Processing	[7]
Adiponectin (ADIPOQ)	OTNX23LE	ADIPO_HUMAN	Gene/Protein Processing	[8]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Protein Interaction/Cellular Processes	[9]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[10]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Gene/Protein Processing	[11]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Gene/Protein Processing	[8]
Dicarboxylate carrier SLC25A8	OTA556MK	UCP2_HUMAN	Gene/Protein Processing	[12]
Equilibrative nucleoside transporter 3 (SLC29A3)	OTGLX8XU	S29A3_HUMAN	Regulation of Drug Effects	[13]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Gene/Protein Processing	[8]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Gene/Protein Processing	[8]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Stavudine

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Cobicistat	DM6L4H2	Moderate	Decreased metabolism of Stavudine caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[14]
Zalcitabine	DMH7MUV	Moderate	Increased risk of peripheral neuropathy by the combination of Stavudine and Zalcitabine.	Human immunodeficiency virus disease [1C60-1C62]	[15]
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Coadministration of a Drug Treating the Disease Different from Stavudine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Stavudine and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[14]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Stavudine and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[16]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Stavudine and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[17]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Stavudine and Cannabidiol.	Epileptic encephalopathy [8A62]	[18]
Ribavirin	DMEYLH9	Moderate	Decreased metabolism of Stavudine caused by Ribavirin.	Hepatitis virus infection [1E50-1E51]	[19]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Stavudine and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[20]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Stavudine and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[21]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Stavudine and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[22]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Stavudine and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[23]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Stavudine and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[24]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Stavudine and Idelalisib.	Mature B-cell leukaemia [2A82]	[25]
Thalidomide	DM70BU5	Moderate	Increased risk of peripheral neuropathy by the combination of Stavudine and Thalidomide.	Multiple myeloma [2A83]	[15]
Orlistat	DMRJSP8	Moderate	Altered absorption of Stavudine caused by Orlistat.	Obesity [5B80-5B81]	[26]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Stavudine and Leflunomide.	Rheumatoid arthritis [FA20]	[22]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Stavudine and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[18]
Naltrexone	DMUL45H	Moderate	Increased risk of hepatotoxicity by the combination of Stavudine and Naltrexone.	Substance abuse [6C40]	[27]
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⏷ Show the Full List of 16 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Allura red AC dye	E00338	33258	Colorant
D&C red no. 28	E00491	6097185	Colorant
FD&C blue no. 1	E00263	19700	Colorant
Quinoline yellow WS	E00309	24671	Colorant
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Sunset yellow FCF	E00255	17730	Colorant
Ammonia	E00007	222	Alkalizing agent
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Magnesium stearate	E00208	11177	lubricant
Potassium hydroxide	E00233	14797	Alkalizing agent
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
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⏷ Show the Full List of 15 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Stavudine 15 mg capsule	15 mg	Oral Capsule	Oral
Stavudine 30 mg capsule	30 mg	Oral Capsule	Oral
Stavudine 20 mg capsule	20 mg	Oral Capsule	Oral
Stavudine 40 mg capsule	40 mg	Oral Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
2	BDDCS applied to over 900 drugs
3	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	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.
7	Lon protease and eiF2 are involved in acute, but not prolonged, antiretroviral induced stress response in HepG2 cells. Chem Biol Interact. 2016 May 25;252:82-6. doi: 10.1016/j.cbi.2016.03.021. Epub 2016 Apr 1.
8	Some HIV antiretrovirals increase oxidative stress and alter chemokine, cytokine or adiponectin production in human adipocytes and macrophages. Antivir Ther. 2007;12(4):489-500.
9	Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. doi: 10.1080/15216540400016286.
10	Stavudine selectively induces apoptosis in HIV type 1-infected cells. AIDS Res Hum Retroviruses. 1997 Jan 20;13(2):193-9. doi: 10.1089/aid.1997.13.193.
11	Longitudinal effects of thymidine analogues on mtDNA, mtRNA and multidrug resistance (MDR-1) induction in cultured cells. J Antimicrob Chemother. 2008 May;61(5):1048-52. doi: 10.1093/jac/dkn067. Epub 2008 Feb 28.
12	Mitochondrial proliferation, DNA depletion and adipocyte differentiation in subcutaneous adipose tissue of HIV-positive HAART recipients. Antivir Ther. 2003 Aug;8(4):323-31.
13	Facilitated mitochondrial import of antiviral and anticancer nucleoside drugs by human equilibrative nucleoside transporter-3. Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G910-22. doi: 10.1152/ajpgi.90672.2008. Epub 2009 Jan 22.
14	Cerner Multum, Inc. "Australian Product Information.".
15	Argov Z, Mastaglia FL "Drug-induced peripheral neuropathies." Br Med J 1 (1979): 663-6. [PMID: 219931]
16	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
17	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
18	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
19	Guyader D, Poinsignon Y, Cano Y, Saout L "Fatal lactic acidosis in a HIV-positive patient treated with interferon and ribavirin for chronic hepatitis C." J Hepatol 37 (2002): 289-91. [PMID: 12127440]
20	Product Information. Accolate (zafirlukast). Zeneca Pharmaceuticals, Wilmington, DE.
21	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
22	Canadian Pharmacists Association.
23	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
24	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
25	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
26	MHRA. Medicines and Healthcare Products Regulatory Agency "Orlistat: theoretical interaction with antiretroviral HIV medicines.".
27	Product Information. ReVia (naltrexone). DuPont Pharmaceuticals, Wilmington, DE.