Valganciclovir

Identification

Summary

Valganciclovir is an antiviral medication used to treat cytomegalovirus (CMV) retinitis in patients diagnosed with acquired immunodeficiency syndrome (AIDS).

Brand Names
Valcyte
Generic Name
Valganciclovir
DrugBank Accession Number
DB01610
Background

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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 354.3617
Monoisotopic: 354.165167844
Chemical Formula
C14H22N6O5
Synonyms
  • Valganciclovir

Pharmacology

Indication

Valganciclovir is an antiviral medication used for the treatment of cytomegalovirus infections.

Pharmacology
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Associated Conditions
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Contraindications
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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.

TargetActionsOrganism
ADNA
adduct
Humans
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]
Adverse Effects
Adverseeffects
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Toxicity

It is expected that an overdose of valganciclovir could also possibly result in increased renal toxicity.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirThe risk or severity of cytopenia can be increased when Valganciclovir is combined with Abacavir.
AceclofenacAceclofenac may decrease the excretion rate of Valganciclovir which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Valganciclovir which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Valganciclovir which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Valganciclovir which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Valganciclovir which could result in a higher serum level.
AclidiniumValganciclovir may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineValganciclovir may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Valganciclovir which could result in a higher serum level.
Adefovir dipivoxilAdefovir dipivoxil may decrease the excretion rate of Valganciclovir which could result in a higher serum level.
Interactions
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Food Interactions
  • Take with food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Valganciclovir hydrochloride4P3T9QF9NZ175865-59-5ZORWARFPXPVJLW-MTFPJWTKSA-N
Active Moieties
NameKindUNIICASInChI Key
GanciclovirprodrugP9G3CKZ4P582410-32-0IRSCQMHQWWYFCW-UHFFFAOYSA-N
Product Images
International/Other Brands
Cymeval / Valcyt
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ValcytePowder, for solution50 mg/1mLOralGenentech, Inc.2009-08-28Not applicableUS flag
ValcytePowder, for solution50 mg / mLOralHoffmann La Roche2008-08-13Not applicableCanada flag
ValcyteTablet, film coated450 mg/1OralGenentech, Inc.2001-03-29Not applicableUS flag
ValcyteTablet450 mgOralHoffmann La Roche2002-07-16Not applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-valganciclovirTablet450 mgOralApotex Corporation2013-07-09Not applicableCanada flag
Auro-valganciclovirTablet450 mgOralAuro Pharma Inc2015-04-10Not applicableCanada flag
Mint-valganciclovirTablet450 mgOralMint Pharmaceuticals Inc2020-05-27Not applicableCanada flag
Mylan-valganciclovirTablet450 mgOralMylan PharmaceuticalsNot applicableNot applicableCanada flag
Nat-valganciclovirTablet450 mgOralNatco Pharma LimitedNot applicableNot applicableCanada flag
Teva-valganciclovirTablet450 mgOralTEVA Canada Limited2014-11-27Not applicableCanada flag
ValganciclovirTablet, film coated450 mg/1Oralbryant ranch prepack2014-11-04Not applicableUS flag
ValganciclovirTablet, film coated450 mg/1OralPar Pharmaceutical2014-11-04Not applicableUS flag00603 6330 20 nlmimage10 d14368cb
ValganciclovirTablet, film coated450 mg/1OralNorthStar Rx LLC2018-03-10Not applicableUS flag
ValganciclovirTablet, film coated450 mg/1OralSafecor Health, LLC2019-05-08Not applicableUS flag

Categories

ATC Codes
J05AB14 — Valganciclovir
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acid esters
Alternative Parents
Valine and derivatives / Purines and purine derivatives / Fatty acid esters / Glycerolipids / Hydroxypyrimidines / N-substituted imidazoles / Heteroaromatic compounds / Carboxylic acid esters / Azacyclic compounds / Monocarboxylic acids and derivatives
show 6 more
Substituents
Alcohol / Alpha-amino acid ester / Amine / Aromatic heteropolycyclic compound / Azacycle / Azole / Carbonyl group / Carboxylic acid ester / Fatty acid ester / Fatty acyl
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
purines, L-valinyl ester (CHEBI:63635)
Affected organisms
  • Human Herpes Virus

Chemical Identifiers

UNII
GCU97FKN3R
CAS number
175865-60-8
InChI Key
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)[C@H](N)C(=O)OCC(CO)OCN1C=NC2=C1NC(N)=NC2=O

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. [Article]
Human Metabolome Database
HMDB0015548
KEGG Drug
D02495
PubChem Compound
64147
PubChem Substance
46505524
ChemSpider
57721
RxNav
275891
ChEBI
63635
ChEMBL
CHEMBL1201314
Therapeutic Targets Database
DAP000646
PharmGKB
PA10227
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Valganciclovir

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedOtherCytomegalovirus (CMV) Infection1
4CompletedPreventionCytomegalovirus Disease1
4CompletedPreventionInfection in Solid Organ Transplant Recipients1
4CompletedPreventionKidney Transplantation, Cytomegalovirus Infections1
4CompletedTreatmentChronic Lymphocytic Leukemia (CLL)1
4CompletedTreatmentCytomegalovirus (CMV) Infection3
4CompletedTreatmentCytomegalovirus (CMV) Infection / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHeart Transplant Recipients / Renal Transplant Recipient Patients1
4CompletedTreatmentInfection in Solid Organ Transplant Recipients1
4CompletedTreatmentKidney Trasplant1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • F Hoffmann-La Roche Ltd.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Patheon Inc.
Dosage Forms
FormRouteStrength
Powder, for solutionOral50 mg / mL
Powder, for solutionOral50 MG/ML
TabletOral450 mg
Tablet, film coatedOral
Powder, for solutionOral
TabletOral450 mg/1
Tablet, film coatedOral450 mg/1
For solutionOral50 mg/1mL
Powder, for solutionOral50 mg/1mL
Tablet, film coatedOral450 mg
Tablet, coatedOral450 mg
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)Region
CA2154721No2001-01-022015-07-26Canada flag
US6083953Yes2000-07-042015-09-29US flag
US9642911No2017-05-092027-12-11US flag
US8889109No2014-11-182027-12-11US flag

Properties

State
Solid
Experimental Properties
Not 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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0239000000-850143c9c0e2faa19d0f
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0gbi-0930000000-c4c88d5b9acc354dad95
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0gb9-0900000000-6c74a9e70b949b0b1a00
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0159-0900000000-a71a2b4b1f37329ca7f0
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0159-1900000000-58d3e9baef3c5fcd5255
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0159-4900000000-dc9a9c630ba915c7aec2

Targets

Drugtargets2
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Kind
Nucleotide
Organism
Humans
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.
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Transporters

Kind
Protein
Organism
Humans
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
Uniprot Name
Solute carrier family 15 member 1
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. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
Solute carrier family 15 member 2
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. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+)
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. [Article]

Drug created on August 29, 2007 19:52 / Updated on October 18, 2021 04:55