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Identification
NameDidanosine
Accession NumberDB00900  (APRD00240, DB02392)
TypeSmall Molecule
GroupsApproved
Description

A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite. [PubChem]

Structure
Thumb
Synonyms
2,3-Dideoxyinosine
9-((2R,5S)-5-(Hydroxymethyl)-tetrahydrofuran-2-yl)-1H-purin-6(9H)-one
9-((2R,5S)-5-Hydroxymethyl-tetrahydro-furan-2-yl)-1,9-dihydro-purin-6-one
9-((2S,5R)-5-Hydroxymethyl-tetrahydro-furan-2-yl)-9H-purin-6-ol
9-[(2R,5S)-5-(Hydroxymethyl)tetrahydrofuran-2-yl]-1,9-dihydro-6H-purin-6-one
DDI
DdIno
Didanosina
Didanosine
Didanosinum
Dideoxyinosine
External Identifiers
  • DDI
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Videxpowder, for solution10 mg/mLoralBristol Myers Squibb Company1991-10-09Not applicableUs
Videxpowder, for solution10 mg/mLoralBristol Myers Squibb Company1991-10-09Not applicableUs
Videx Chewable Dispersible Tab 100mgtablet100 mgoralBristol Myers Squibb Canada1991-12-312008-03-27Canada
Videx Chewable Dispersible Tab 150mgtablet150 mgoralBristol Myers Squibb Canada1991-12-312007-05-01Canada
Videx Chewable Dispersible Tab 25mgtablet25 mgoralBristol Myers Squibb Canada1991-12-312007-01-02Canada
Videx Chewable Dispersible Tab 50mgtablet50 mgoralBristol Myers Squibb Canada1991-12-312005-08-01Canada
Videx ECcapsule (enteric-coated)125 mgoralBristol Myers Squibb Canada2002-01-02Not applicableCanada
Videx ECcapsule, delayed release400 mg/1oralBristol Myers Squibb Company2000-10-31Not applicableUs
Videx ECcapsule, delayed release250 mg/1oralBristol Myers Squibb Company2000-10-31Not applicableUs
Videx ECcapsule, delayed release200 mg/1oralBristol Myers Squibb Company2000-10-31Not applicableUs
Videx ECcapsule (enteric-coated)400 mgoralBristol Myers Squibb Canada2002-01-02Not applicableCanada
Videx ECcapsule, delayed release125 mg/1oralBristol Myers Squibb Company2000-10-31Not applicableUs
Videx ECcapsule (enteric-coated)250 mgoralBristol Myers Squibb Canada2002-01-02Not applicableCanada
Videx ECcapsule (enteric-coated)200 mgoralBristol Myers Squibb Canada2002-01-02Not applicableCanada
Videx Pediatric Powder Sol 4g/bottpowder for solution4 goralBristol Myers Squibb Canada1999-07-012007-06-28Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Didanosinecapsule, delayed release400 mg/1oralAurobindo Pharma Limited2008-09-24Not applicableUs
Didanosinecapsule, delayed release125 mg/1oralMylan Pharmaceuticals Inc.2010-06-28Not applicableUs
Didanosinecapsule, delayed release400 mg/1oralAmerican Health Packaging2009-12-082015-12-29Us
Didanosinecapsule, delayed release pellets400 mg/1oralBarr Laboratories Inc.2004-12-15Not applicableUs
Didanosinecapsule, delayed release250 mg/1oralAurobindo Pharma Limited2008-09-24Not applicableUs
Didanosinecapsule, delayed release pellets250 mg/1oralBarr Laboratories Inc.2004-12-15Not applicableUs
Didanosinecapsule, delayed release200 mg/1oralAurobindo Pharma Limited2008-09-24Not applicableUs
Didanosinecapsule, delayed release pellets200 mg/1oralBarr Laboratories Inc.2004-12-15Not applicableUs
Didanosinecapsule, delayed release125 mg/1oralAurobindo Pharma Limited2008-09-24Not applicableUs
Didanosinecapsule, delayed release400 mg/1oralMylan Pharmaceuticals Inc.2010-06-28Not applicableUs
Didanosinecapsule, delayed release pellets250 mg/1oralPhysicians Total Care, Inc.2007-12-13Not applicableUs
Didanosinecapsule, delayed release250 mg/1oralMylan Pharmaceuticals Inc.2010-06-28Not applicableUs
Didanosinecapsule, delayed release400 mg/1oralAmerican Health Packaging2009-12-082015-12-29Us
Didanosinecapsule, delayed release pellets400 mg/1oralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
Didanosinecapsule, delayed release250 mg/1oralAmerican Health Packaging2009-12-082015-12-29Us
Didanosinecapsule, delayed release200 mg/1oralMylan Pharmaceuticals Inc.2010-06-28Not applicableUs
Didanosinecapsule, delayed release250 mg/1oralAmerican Health Packaging2009-12-082015-12-29Us
Didanosinecapsule, delayed release pellets250 mg/1oralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIK3GDH6OH08
CAS number69655-05-6
WeightAverage: 236.2273
Monoisotopic: 236.09094027
Chemical FormulaC10H12N4O3
InChI KeyInChIKey=BXZVVICBKDXVGW-NKWVEPMBSA-N
InChI
InChI=1S/C10H12N4O3/c15-3-6-1-2-7(17-6)14-5-13-8-9(14)11-4-12-10(8)16/h4-7,15H,1-3H2,(H,11,12,16)/t6-,7+/m0/s1
IUPAC Name
9-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]-6,9-dihydro-3H-purin-6-one
SMILES
OC[C@@H]1CC[C@@H](O1)N1C=NC2=C1NC=NC2=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as purine 3'-deoxyribonucleosides. These are compounds consisting of a purine linked to a ribose which lacks a hydroxyl group at position 3.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassPurine nucleosides
Sub ClassPurine 3'-deoxyribonucleosides
Direct ParentPurine 3'-deoxyribonucleosides
Alternative Parents
Substituents
  • Purine 3'-deoxyribonucleoside
  • Purinone
  • Hypoxanthine
  • 6-oxopurine
  • Purine
  • Imidazopyrimidine
  • Pyrimidone
  • Pyrimidine
  • N-substituted imidazole
  • Heteroaromatic compound
  • Vinylogous amide
  • Oxolane
  • Imidazole
  • Azole
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor use, in combination with other antiretroviral agents, in the treatment of HIV-1 infection in adults.
PharmacodynamicsDidanosine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Didanosine differs from other nucleoside analogues, as it does not have any of the regular bases, instead it has hypoxanthine attached to the sugar ring. Didanosine 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. Didanosine is effective against HIV, and usually used in combination with other antiviral therapy. Switching from long term AZT treatment to didanosine has been shown to be beneficial. Didanosine has weak acid stability and therefore, it is often combined with an antacid.
Mechanism of actionDidanosine (ddI) is metabolized intracellularly by a series of cellular enzymes to its active moiety, dideoxyadenosine triphosphate (ddATP), which inhibits the HIV reverse transcriptase enzyme competitively by competing with natural dATP. It also acts as a chain terminator by its incorporation into viral DNA as 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.
Related Articles
AbsorptionRapidly absorbed (bioavailability 30-40%) with peak plasma concentrations appearing within 0.5 and 1.5 hrs.
Volume of distributionNot Available
Protein bindingLow (<5%)
Metabolism

Rapidly metabolized intracellularly to its active moiety, 2,3-dideoxyadenosine-5-triphosphate (ddA-TP). It is then further metabolized hepatically to yield hypoxanthine, xanthine, and uric acid.

SubstrateEnzymesProduct
Didanosine
Not Available
HypoxanthineDetails
Didanosine
Not Available
Uric acidDetails
Didanosine
Not Available
XanthineDetails
Didanosine
Not Available
2,3-dideoxyadenosine-5-triphosphateDetails
Route of eliminationBased on data from in vitro and animal studies, it is presumed that the metabolism of didanosine in man occurs by the same pathways responsible for the elimination of endogenous purines. Purines are eliminated by the kidneys.
Half life30 minutes in plasma and more than 12 hours in intracellular environment.
ClearanceNot Available
ToxicitySide effects include pancreatitis, peripheral neuropathy, diarrhea, hyperuricemia and hepatic dysfunction
Affected organisms
  • Human Immunodeficiency Virus
Pathways
PathwayCategorySMPDB ID
Didanosine Action PathwayDrug actionSMP00739
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.996
Blood Brain Barrier+0.823
Caco-2 permeable-0.9019
P-glycoprotein substrateNon-substrate0.5948
P-glycoprotein inhibitor INon-inhibitor0.945
P-glycoprotein inhibitor IINon-inhibitor0.6378
Renal organic cation transporterNon-inhibitor0.8049
CYP450 2C9 substrateNon-substrate0.8065
CYP450 2D6 substrateNon-substrate0.7777
CYP450 3A4 substrateNon-substrate0.5234
CYP450 1A2 substrateNon-inhibitor0.6934
CYP450 2C9 inhibitorNon-inhibitor0.9064
CYP450 2D6 inhibitorNon-inhibitor0.9145
CYP450 2C19 inhibitorNon-inhibitor0.8646
CYP450 3A4 inhibitorNon-inhibitor0.9608
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7288
Ames testAMES toxic0.8682
CarcinogenicityNon-carcinogens0.9094
BiodegradationNot ready biodegradable0.8478
Rat acute toxicity2.0874 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9451
hERG inhibition (predictor II)Non-inhibitor0.8735
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Aurobindo pharma ltd
  • Barr laboratories inc
  • Matrix laboratories ltd
  • Bristol myers squibb co
  • Bristol myers squibb co pharmaceutical research institute
Packagers
Dosage forms
FormRouteStrength
Capsule, delayed release pelletsoral200 mg/1
Capsule, delayed release pelletsoral250 mg/1
Capsule, delayed release pelletsoral400 mg/1
Powder, for solutionoral10 mg/mL
Tabletoral100 mg
Tabletoral150 mg
Tabletoral25 mg
Tabletoral50 mg
Capsule (enteric-coated)oral125 mg
Capsule (enteric-coated)oral200 mg
Capsule (enteric-coated)oral250 mg
Capsule (enteric-coated)oral400 mg
Capsule, delayed releaseoral125 mg/1
Capsule, delayed releaseoral200 mg/1
Capsule, delayed releaseoral250 mg/1
Capsule, delayed releaseoral400 mg/1
Powder for solutionoral4 g
Prices
Unit descriptionCostUnit
Videx 4 gm Solution 200ml Bottle124.51USD bottle
Videx 2 gm Solution 100ml Bottle58.4USD bottle
Videx EC 400 mg Delayed Release Capsule14.75USD capsule
Videx ec 400 mg capsule14.18USD capsule
Didanosine 400 mg Delayed Release Capsule12.78USD capsule
Videx EC 250 mg Delayed Release Capsule9.44USD capsule
Videx ec 250 mg capsule9.08USD capsule
Didanosine 250 mg Delayed Release Capsule8.18USD capsule
Videx ec 200 mg capsule7.12USD capsule
Didanosine 200 mg Delayed Release Capsule6.42USD capsule
Videx ec 125 mg capsule4.45USD capsule
Videx 4 gm pediatric solution0.6USD ml
Videx 2 gm pediatric solution0.55USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2072573 No1996-05-282011-01-03Canada
CA2332922 No2008-02-122018-08-04Canada
US5880106 No1995-01-222012-01-22Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point160-163 °CPhysProp
water solubility15.8 mg/mLNot Available
logP-1.24SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility6.58 mg/mLALOGPS
logP-0.99ALOGPS
logP-0.35ChemAxon
logS-1.6ALOGPS
pKa (Strongest Acidic)6.94ChemAxon
pKa (Strongest Basic)2.75ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area88.74 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity58.59 m3·mol-1ChemAxon
Polarizability22.9 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Bandi Parthasaradhi Reddy, Kura Rathnakar Reddy, Rapolu Raji Reddy, Dasari Muralidhara Reddy, Kesireddy Subash Chander Reddy, “Novel Process for the Preparation of Didanosine Using Novel Intermediates.” U.S. Patent US20080293938, issued November 27, 2008.

US20080293938
General ReferencesNot Available
External Links
ATC CodesJ05AF02
AHFS Codes
  • 08:18.08.20
PDB Entries
FDA labelDownload (86.1 KB)
MSDSDownload (36.5 KB)
Interactions
Drug Interactions
Drug
AllopurinolThe serum concentration of Didanosine can be increased when it is combined with Allopurinol.
AtazanavirThe serum concentration of Atazanavir can be decreased when it is combined with Didanosine.
CiprofloxacinThe serum concentration of Didanosine can be decreased when it is combined with Ciprofloxacin.
DarunavirThe serum concentration of Didanosine can be decreased when it is combined with Darunavir.
EthanolThe risk or severity of adverse effects can be increased when Ethanol is combined with Didanosine.
FebuxostatThe serum concentration of Didanosine can be increased when it is combined with Febuxostat.
FluconazoleDidanosine can cause a decrease in the absorption of Fluconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
GanciclovirThe risk or severity of adverse effects can be increased when Ganciclovir is combined with Didanosine.
GemifloxacinThe serum concentration of Didanosine can be decreased when it is combined with Gemifloxacin.
HydroxyureaThe risk or severity of adverse effects can be increased when Hydroxyurea is combined with Didanosine.
IndinavirThe serum concentration of Indinavir can be decreased when it is combined with Didanosine.
ItraconazoleDidanosine can cause a decrease in the absorption of Itraconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
KetoconazoleDidanosine can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
LevofloxacinThe serum concentration of Didanosine can be decreased when it is combined with Levofloxacin.
LopinavirThe serum concentration of Didanosine can be decreased when it is combined with Lopinavir.
MethadoneThe serum concentration of Didanosine can be decreased when it is combined with Methadone.
MoxifloxacinThe serum concentration of Didanosine can be decreased when it is combined with Moxifloxacin.
NorfloxacinThe serum concentration of Didanosine can be decreased when it is combined with Norfloxacin.
OfloxacinThe serum concentration of Didanosine can be decreased when it is combined with Ofloxacin.
PosaconazoleDidanosine can cause a decrease in the absorption of Posaconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
RibavirinThe risk or severity of adverse effects can be increased when Ribavirin is combined with Didanosine.
RilpivirineRilpivirine can cause a decrease in the absorption of Didanosine resulting in a reduced serum concentration and potentially a decrease in efficacy.
SparfloxacinThe serum concentration of Didanosine can be decreased when it is combined with Sparfloxacin.
StavudineThe risk or severity of adverse effects can be increased when Stavudine is combined with Didanosine.
TenofovirThe therapeutic efficacy of Didanosine can be decreased when used in combination with Tenofovir.
TipranavirThe serum concentration of Didanosine can be decreased when it is combined with Tipranavir.
VoriconazoleDidanosine can cause a decrease in the absorption of Voriconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Food Interactions
  • Avoid alcohol.
  • Take on empty stomach: 1 hour before or 2 hours after meals.

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. Faulds D, Brogden RN: Didanosine. A review of its antiviral activity, pharmacokinetic properties and therapeutic potential in human immunodeficiency virus infection. Drugs. 1992 Jul;44(1):94-116. [PubMed:1379914 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Purine-nucleoside phosphorylase activity
Specific Function:
The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.
Gene Name:
PNP
Uniprot ID:
P00491
Molecular Weight:
32117.69 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]

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:
Nucleoside transmembrane transporter activity
Specific Function:
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR) and is sodium-independent. It has a higher affinity for adenosine. Inhibited by dipyridamole and dilazep (anticancer chemotherapeutics drugs).
Gene Name:
SLC29A1
Uniprot ID:
Q99808
Molecular Weight:
50218.805 Da
References
  1. Yao SY, Ng AM, Sundaram M, Cass CE, Baldwin SA, Young JD: Transport of antiviral 3'-deoxy-nucleoside drugs by recombinant human and rat equilibrative, nitrobenzylthioinosine (NBMPR)-insensitive (ENT2) nucleoside transporter proteins produced in Xenopus oocytes. Mol Membr Biol. 2001 Apr-Jun;18(2):161-7. [PubMed:11463208 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Nucleoside transmembrane transporter activity
Specific Function:
Mediates equilibrative transport of purine, pyrimidine nucleosides and the purine base hypoxanthine. Very less sensitive than SLC29A1 to inhibition by nitrobenzylthioinosine (NBMPR), dipyridamole, dilazep and draflazine.
Gene Name:
SLC29A2
Uniprot ID:
Q14542
Molecular Weight:
50112.335 Da
References
  1. Yao SY, Ng AM, Sundaram M, Cass CE, Baldwin SA, Young JD: Transport of antiviral 3'-deoxy-nucleoside drugs by recombinant human and rat equilibrative, nitrobenzylthioinosine (NBMPR)-insensitive (ENT2) nucleoside transporter proteins produced in Xenopus oocytes. Mol Membr Biol. 2001 Apr-Jun;18(2):161-7. [PubMed:11463208 ]
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12