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Identification
NameValganciclovir
Accession NumberDB01610
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionValganciclovir 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
Synonyms
Cymeval
L-valine, ester with ganciclovir
Valcyte
Valganciclovir
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Auro-valganciclovirtablet450 mgoralAuro Pharma Inc2015-04-10Not applicableCanada
Mylan-valganciclovirtablet450 mgoralMylan Pharmaceuticals UlcNot applicableNot applicableCanada
Teva-valganciclovirtablet450 mgoralTeva Canada Limited2014-11-27Not applicableCanada
Valcytetablet, film coated450 mg/1oralGenentech, Inc.2001-03-29Not applicableUs
Valcytepowder, for solution50 mg/mLoralGenentech, Inc.2009-08-28Not applicableUs
Valcytetablet450 mgoralHoffmann La Roche Limited2002-07-16Not applicableCanada
Valcytepowder for solution50 mgoralHoffmann La Roche Limited2008-08-13Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-valganciclovirtablet450 mgoralApotex Inc2013-07-09Not applicableCanada
Valganciclovirtablet, film coated450 mg/1oralQualitest Pharmaceuticals2014-11-04Not applicableUs
Valganciclovirtablet, film coated450 mg/1oralCamber Pharmaceuticals, Inc.2016-03-18Not applicableUs
Valganciclovirtablet, film coated450 mg/1oralDr. Reddy's Laboratories Limited2014-12-15Not applicableUs
Valganciclovirtablet, film coated450 mg/1oralAmerican Health Packaging2015-01-15Not applicableUs
Valganciclovir Hydrochloridetablet450 mg/1oralAurobindo Pharma Limited2016-03-31Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CymevalNot Available
ValcytNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Valganciclovir hydrochloride
ThumbNot applicableDBSALT001459
Categories
UNIIGCU97FKN3R
CAS number175865-60-8
WeightAverage: 354.3617
Monoisotopic: 354.165167844
Chemical FormulaC14H22N6O5
InChI KeyInChIKey=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
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)[[email protected]](N)C(=O)OCC(CO)OCN1C=NC2=C1NC(N)=NC2=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acid esters
Alternative Parents
Substituents
  • Alpha-amino acid ester
  • Hypoxanthine
  • 6-oxopurine
  • Purine
  • Imidazopyrimidine
  • Glycerolipid
  • Glycerol ether
  • Pyrimidone
  • Fatty acid ester
  • Fatty acyl
  • Pyrimidine
  • Primary aromatic amine
  • N-substituted imidazole
  • Heteroaromatic compound
  • Vinylogous amide
  • Imidazole
  • Azole
  • Carboxylic acid ester
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Primary amine
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationValganciclovir is an antiviral medication used for the treatment of cytomegalovirus infections.
PharmacodynamicsValganciclovir 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 actionValganciclovir 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.
Related Articles
AbsorptionValganciclovir 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 bindingPlasma 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 eliminationThe major route of elimination of valganciclovir is by renal excretion as ganciclovir through glomerular filtration and active tubular secretion.
Half lifeApproximately 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]
ToxicityIt is expected that an overdose of valganciclovir could also possibly result in increased renal toxicity.
Affected organisms
  • Human Herpes Virus
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9104
Blood Brain Barrier+0.9383
Caco-2 permeable-0.8874
P-glycoprotein substrateSubstrate0.6534
P-glycoprotein inhibitor INon-inhibitor0.9314
P-glycoprotein inhibitor IINon-inhibitor0.9395
Renal organic cation transporterNon-inhibitor0.9026
CYP450 2C9 substrateNon-substrate0.8915
CYP450 2D6 substrateNon-substrate0.8351
CYP450 3A4 substrateNon-substrate0.5362
CYP450 1A2 substrateNon-inhibitor0.8981
CYP450 2C9 inhibitorNon-inhibitor0.8585
CYP450 2D6 inhibitorNon-inhibitor0.889
CYP450 2C19 inhibitorNon-inhibitor0.8334
CYP450 3A4 inhibitorNon-inhibitor0.9232
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.918
Ames testNon AMES toxic0.6023
CarcinogenicityNon-carcinogens0.8588
BiodegradationNot ready biodegradable0.9356
Rat acute toxicity2.1981 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9804
hERG inhibition (predictor II)Non-inhibitor0.8918
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Powder for solutionoral50 mg
Powder, for solutionoral50 mg/mL
Tabletoral450 mg
Tablet, film coatedoral450 mg/1
Tabletoral450 mg/1
Prices
Unit descriptionCostUnit
Valcyte48.87USD tablet
Valcyte 450 mg tablet46.99USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2154721 No2001-01-022015-07-26Canada
US6083953 Yes1995-09-292015-09-29Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility4.79 mg/mLALOGPS
logP-0.81ALOGPS
logP-1.1ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)8.1ChemAxon
pKa (Strongest Basic)7.36ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area167.08 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity86.6 m3·mol-1ChemAxon
Polarizability34.88 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

Romi Singh, Vishnubhotla Nagaprasad, Nidhi Singh, “Processes for the Preparation of Solid Dosage Forms of Amorphous Valganciclovir Hydrochloride.” U.S. Patent US20070292499, issued December 20, 2007.

US20070292499
General References
  1. Umapathy NS, Ganapathy V, Ganapathy ME: Transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the amino acid transporter ATB(0,+). Pharm Res. 2004 Jul;21(7):1303-10. [PubMed:15290873 ]
External Links
ATC CodesJ05AB14
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
adduct
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
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. doi: 10.3851/IMP1565. [PubMed:20587851 ]
  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:16173018 ]
  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:17157554 ]
  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:16906040 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function:
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name:
SLC15A1
Uniprot ID:
P46059
Molecular Weight:
78805.265 Da
References
  1. Sugawara M, Huang W, Fei YJ, Leibach FH, Ganapathy V, Ganapathy ME: Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J Pharm Sci. 2000 Jun;89(6):781-9. [PubMed:10824137 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Peptide:proton symporter activity
Specific Function:
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
Gene Name:
SLC15A2
Uniprot ID:
Q16348
Molecular Weight:
81782.77 Da
References
  1. Sugawara M, Huang W, Fei YJ, Leibach FH, Ganapathy V, Ganapathy ME: Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J Pharm Sci. 2000 Jun;89(6):781-9. [PubMed:10824137 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Neurotransmitter:sodium symporter activity
Specific Function:
Mediates the uptake of a broad range of neutral and cationic amino acids (with the exception of proline) in a Na(+)/Cl(-)-dependent manner.
Gene Name:
SLC6A14
Uniprot ID:
Q9UN76
Molecular Weight:
72152.145 Da
References
  1. Umapathy NS, Ganapathy V, Ganapathy ME: Transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the amino acid transporter ATB(0,+). Pharm Res. 2004 Jul;21(7):1303-10. [PubMed:15290873 ]
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Drug created on August 29, 2007 13:52 / Updated on September 30, 2016 02:27