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targets (2) transporters (1)
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Identification
Name Didanosine
Accession Number DB00900 (APRD00240, DB02392)
Type small molecule
Groups approved
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A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen.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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • DDI
  • Dideoxyinosine
Brand names
  • Videx
  • Videx EC
Brand name mixtures Not Available
Categories
  • Anti-HIV Agents
  • Antimetabolites
  • Reverse Transcriptase Inhibitors
  • Purine Nucleoside Phosphorylase inhibitor
CAS number 69655-05-6
Weight Average: 236.2273
Monoisotopic: 236.090940270
Chemical Formula C10H12N4O3
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes Not Available
Substructures
  • Hydroxy Compounds
  • Ethers
  • Alcohols and Polyols
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Furans
  • Cyanamides
  • Hypoxanthines
  • Inosines
Pharmacology
Indication For use, in combination with other antiretroviral agents, in the treatment of HIV-1 infection in adults.
Pharmacodynamics Didanosine 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 action Didanosine (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.
Absorption Rapidly absorbed (bioavailability 30-40%) with peak plasma concentrations appearing within 0.5 and 1.5 hrs.
Volume of distribution Not Available
Protein binding Low (<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.
Route of elimination Based 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 life 30 minutes in plasma and more than 12 hours in intracellular environment.
Clearance Not Available
Toxicity Side effects include pancreatitis, peripheral neuropathy, diarrhea, hyperuricemia and hepatic dysfunction
Affected organisms
  • Human Immunodeficiency Virus
Pathways Not Available
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
Form Route Strength
Capsule, coated Oral
Powder, for solution Oral
Tablet Oral
Prices
Unit description Cost Unit
Videx 4 gm Solution 200ml Bottle 124.51 USD bottle
Videx 2 gm Solution 100ml Bottle 58.4 USD bottle
Videx EC 400 mg Delayed Release Capsule 14.75 USD capsule
Videx ec 400 mg capsule 14.18 USD capsule
Didanosine 400 mg Delayed Release Capsule 12.78 USD capsule
Videx EC 250 mg Delayed Release Capsule 9.44 USD capsule
Videx ec 250 mg capsule 9.08 USD capsule
Didanosine 250 mg Delayed Release Capsule 8.18 USD capsule
Videx ec 200 mg capsule 7.12 USD capsule
Didanosine 200 mg Delayed Release Capsule 6.42 USD capsule
Videx ec 125 mg capsule 4.45 USD capsule
Videx 4 gm pediatric solution 0.6 USD ml
Videx 2 gm pediatric solution 0.55 USD ml
Patents
Country Patent Number Approved Expires
United States 5880106 1995-01-22 2012-01-22
Canada 2332922 2008-02-12 2018-08-04
Canada 2072573 1996-05-28 2011-01-03
Properties
State solid
Melting point 160-163 oC
Experimental Properties
Property Value Source
water solubility 15.8 mg/mL PhysProp
logP -0.2 PhysProp
Predicted Properties
Property Value Source
water solubility 6.58e+00 g/l ALOGPS
logP -0.99 ALOGPS
logP -0.35 ChemAxon Molconvert
logS -1.55 ALOGPS
pKa 14.67 ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 88.74 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 58.59 ChemAxon Molconvert
polarizability 22.90 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00296 Link_out
KEGG Compound C06953 Link_out
PubChem Compound 50599 Link_out
PubChem Substance 46506255 Link_out
ChemSpider 45864 Link_out
ChEBI 490877 Link_out
ChEMBL 490877 Link_out
Therapeutic Targets Database DNC000528 Link_out
PharmGKB PA449301 Link_out
HET 2DI Link_out
Drug Product Database 2244596 Link_out
RxList http://www.rxlist.com/cgi/generic3/didanosine.htm Link_out
Drugs.com http://www.drugs.com/cdi/didanosine-chewable-dispersible-buffered-tablets.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/vid1482.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Didanosine Link_out
ATC Codes
  • J05AF02
AHFS Codes
  • 08:18.08.20
PDB Entries
FDA label show (86.1 KB)
MSDS show (36.5 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Take on empty stomach: 1 hour before or 2 hours after meals.
Targets

1. Reverse transcriptase

Pharmacological action: yes
Actions: inhibitor
UniProt ID: Q5DNL9 Link_out

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
  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
  3. Barry M, Gibbons S, Back D, Mulcahy F: Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations. Clin Pharmacokinet. 1997 Mar;32(3):194-209. Pubmed
  4. Frankel FA, Marchand B, Turner D, Gotte M, Wainberg MA: Impaired rescue of chain-terminated DNA synthesis associated with the L74V mutation in human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother. 2005 Jul;49(7):2657-64. Pubmed
  5. Idzik KR, Cywinski PJ, Cranfield CG, Mohr GJ, Beckert R: Molecular Recognition of the Antiretroviral Drug Abacavir: Towards the Development of a Novel Carbazole-Based Fluorosensor. J Fluoresc. 2011 Jan 11. Pubmed
  6. Hazen R, Harvey R, Ferris R, Craig C, Yates P, Griffin P, Miller J, Kaldor I, Ray J, Samano V, Furfine E, Spaltenstein A, Hale M, Tung R, St Clair M, Hanlon M, Boone L: In vitro antiviral activity of the novel, tyrosyl-based human immunodeficiency virus (HIV) type 1 protease inhibitor brecanavir (GW640385) in combination with other antiretrovirals and against a panel of protease inhibitor-resistant HIV. Antimicrob Agents Chemother. 2007 Sep;51(9):3147-54. Epub 2007 Jul 9. Pubmed

2. Purine nucleoside phosphorylase

Pharmacological action: unknown
Organism class: human
UniProt ID: P00491 Link_out
Gene: NP Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
Transporters

1. Solute carrier family 22 member 6

Actions: substrate
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on July 18, 2011 11:22

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.