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Identification
Name Valganciclovir
Accession Number DB01610
Type small molecule
Groups approved
Description

Valganciclovir hydrochloride (Valcyte, manufactured by Roche) is an antiviral medication used to treat cytomegalovirus infections. As the L-valyl ester of ganciclovir, it is actually a prodrug for ganciclovir. After oral administration, it is rapidly converted to ganciclovir by intestinal and hepatic esterases.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Cymeval
  • L-valine, ester with ganciclovir
  • valganciclovir
Brand names
  • Cymeval
  • Valcyt
  • Valcyte
Brand name mixtures Not Available
Categories
  • Antiviral Agents
CAS number 175865-60-8
Weight Average: 354.3617
Monoisotopic: 354.165167844
Chemical Formula C14H22N6O5
InChI Key InChIKey=WPVFJKSGQUFQAP-GKAPJAKFSA-N
InChI
InChI=1S/C14H22N6O5/c1-7(2)9(15)13(23)24-4-8(3-21)25-6-20-5-17-10-11(20)18-14(16)19-12(10)22/h5,7-9,21H,3-4,6,15H2,1-2H3,(H3,16,18,19,22)/t8?,9-/m0/s1
Plain Text
IUPAC Name
2-[(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)methoxy]-3-hydroxypropyl (2S)-2-amino-3-methylbutanoate
SMILES
CC(C)[C@H](N)C(=O)OCC(CO)OCN1C=NC2=C1NC(N)=NC2=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Hypoxanthines
Substructures
  • Carboxylic Acids and Derivatives
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Ethers
  • Alcohols and Polyols
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Cyanamides
  • Hypoxanthines
Pharmacology
Indication Valganciclovir is an antiviral medication used for the treatment of cytomegalovirus infections.
Pharmacodynamics Valganciclovir is an antiviral medication used to treat cytomegalovirus infections. As the L-valyl ester of ganciclovir, it is actually a prodrug for ganciclovir. After oral administration, it is rapidly converted to ganciclovir by intestinal and hepatic esterases. After this, it (being an analogue of guanosine) gets incorporated into DNA and thus cannot be properly read by DNA polymerase. This results in the termination of the elongation of viral DNA.
Mechanism of action Valganciclovir is a prodrug of ganciclovir that exists as a mixture of two diastereomers. After administration, these diastereomers are rapidly converted to ganciclovir by hepatic and intestinal esterases. In cytomegalovirus (CMV)-infected cells, ganciclovir is initially phosphorylated to the monophosphate form by viral protein kinase, then it is further phosphorylated via cellular kinases to produce the triphosphate form. This triphosphate form is slowly metabolized intracellularly. The phosphorylation is dependent upon the viral kinase and occurs preferentially in virus-infected cells. The virustatic activity of ganciclovir is due to the inhibition of viral DNA synthesis by ganciclovir triphosphate. Ganciclovir triphosphate is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand. Ganciclovir inhibits viral DNA polymerases more effectively than it does cellular polymerase, and chain elongation resumes when ganciclovir is removed.
Absorption Valganciclovir is well absorbed from the gastrointestinal tract and the absolute bioavailability from valganciclovir tablets (following administration with food) is approximately 60%.
Volume of distribution
  • 0.703 ± 0.134 L/kg
Protein binding Plasma protein binding of ganciclovir is 1% to 2% over concentrations of 0.5 and 51 mg/mL.
Metabolism

Rapidly hydrolyzed in the intestinal wall and liver to ganciclovir. No other metabolites have been detected.
Route of elimination The major route of elimination of valganciclovir is by renal excretion as ganciclovir through glomerular filtration and active tubular secretion.
Half life Approximately 4.08 hours. Increased in patients with renal function impairment.
Clearance
  • 3.07+/- 0.64 mL/min/kg [IV administration]
  • 5.3 L/hr [Patient with creatinine clearance of 70.4 mL/min]
Toxicity It is expected that an overdose of valganciclovir could also possibly result in increased renal toxicity.
Affected organisms
  • Human Herpes Virus
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Roche palo alto llc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Valcyte 48.87 USD tablet
Valcyte 450 mg tablet 46.99 USD tablet
Patents
Country Patent Number Approved Expires
United States 6083953 1995-09-29 2015-09-29
Canada 2154721 2001-01-02 2015-07-26
Properties
State solid
Melting point Not Available
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility 4.79e+00 g/l ALOGPS
logP -0.81 ALOGPS
logP -1.09 ChemAxon Molconvert
logS -1.87 ALOGPS
pKa 14.60 ChemAxon Molconvert
hydrogen acceptor count 9 ChemAxon Molconvert
hydrogen donor count 4 ChemAxon Molconvert
polar surface area 167.08 ChemAxon Molconvert
rotatable bond count 9 ChemAxon Molconvert
refractivity 86.60 ChemAxon Molconvert
polarizability 34.88 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
PubChem Compound 64147 Link_out
PubChem Substance 46505524 Link_out
ChemSpider 57721 Link_out
Therapeutic Targets Database DAP000646 Link_out
PharmGKB PA10227 Link_out
Drug Product Database 2245777 Link_out
RxList http://www.rxlist.com/cgi/generic/valganciclovir.htm Link_out
Drugs.com http://www.drugs.com/cdi/valganciclovir.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/val1584.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Valganciclovir Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. DNA

Pharmacological action: yes
Actions: adduct

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

Gene Sequence: FASTA

References:
  1. Martin M, Azzi A, Lin SX, Boivin G: Opposite effect of two cytomegalovirus DNA polymerase mutations on replicative capacity and polymerase activity. Antivir Ther. 2010;15(4):579-86. Pubmed
  2. Boivin G, Goyette N, Gilbert C, Covington E: Analysis of cytomegalovirus DNA polymerase (UL54) mutations in solid organ transplant patients receiving valganciclovir or ganciclovir prophylaxis. J Med Virol. 2005 Nov;77(3):425-9. Pubmed
  3. Marfori JE, Exner MM, Marousek GI, Chou S, Drew WL: Development of new cytomegalovirus UL97 and DNA polymerase mutations conferring drug resistance after valganciclovir therapy in allogeneic stem cell recipients. J Clin Virol. 2007 Feb;38(2):120-5. Epub 2006 Dec 8. Pubmed
  4. Potena L, Holweg CT, Chin C, Luikart H, Weisshaar D, Narasimhan B, Fearon WF, Lewis DB, Cooke JP, Mocarski ES, Valantine HA: Acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection. Transplantation. 2006 Aug 15;82(3):398-405. Pubmed
Comments
Drug created on August 29, 2007 13:52 / Updated on November 10, 2010 13:50

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.