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Identification
NameGanciclovir
Accession NumberDB01004  (APRD00263, EXPT01540)
TypeSmall Molecule
GroupsApproved, Investigational
Description

An acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [PubChem]

Structure
Thumb
Synonyms
2-(6-Amino-purin-9-ylmethoxy)-propane-1,3-diol
2-amino-9-((1,3-Dihydroxypropan-2-yloxy)methyl)-1H-purin-6(9H)-one
2-amino-9-((1,3-Dihydroxypropan-2-yloxy)methyl)-3H-purin-6(9H)-one
2-amino-9-((1,3-Dihydroxypropan-2-yloxy)methyl)-9H-purin-6-ol
2-Amino-9-(2-hydroxy-1-hydroxymethyl-ethoxymethyl)-1,9-dihydro-purin-6-one
2-amino-9-(2-Hydroxy-1-hydroxymethylethoxymethyl)-6,9-dihydro-1H-6-purinone
9-((2-Hydroxy-1-(hydroxymethyl)ethoxy)methyl)guanine
9-[(1,3-dihydroxy-2-propoxy)methyl]guanine
GA2
Ganciclovir
Ganciclovirum
Gancyclovir
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cytovene - Cap 250mgcapsule250 mgoralHoffmann La Roche Limited1995-12-312007-08-02Canada
Cytovene - Pws 500mg/10m/-vial IVpowder for solution500 mgintravenousHoffmann La Roche Limited1995-12-31Not applicableCanada
Cytovene Inj 500mg/vialpowder for solution500 mgintravenousSyntex Inc.1990-12-311996-09-30Canada
Cytovene IVinjection, powder, lyophilized, for solution500 mg/10mLintravenousGenentech, Inc.1989-06-23Not applicableUs
Cytovene, 500 mgcapsule500 mgoralHoffmann La Roche Limited2000-01-142007-08-02Canada
Ganciclovir for Injectionpowder for solution500 mgintravenousFresenius Kabi Canada Ltd2014-04-08Not applicableCanada
Vitrasert, Intravitreal Implantimplant4.5 mgintravitrealBausch & Lomb Inc1998-03-252008-07-28Canada
Zirgangel1.5 mg/gophthalmicBausch & Lomb Incorporated2010-04-30Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ganciclovircapsule250 mg/1oralRanbaxy Pharmaceuticals Inc.2003-08-27Not applicableUs
Ganciclovirinjection, powder, lyophilized, for solution500 mg/10mLintravenousAPP Pharmaceuticals, LLC2010-06-28Not applicableUs
Ganciclovircapsule500 mg/1oralRanbaxy Pharmaceuticals Inc.2003-08-27Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CytoveneNot Available
VitrasertNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Ganciclovir Sodium
Thumb
  • InChI Key: JJICLMJFIKGAAU-UHFFFAOYSA-M
  • Monoisotopic Mass: 277.078698572
  • Average Mass: 277.2124
DBSALT000309
Categories
UNIIP9G3CKZ4P5
CAS number82410-32-0
WeightAverage: 255.2306
Monoisotopic: 255.096753929
Chemical FormulaC9H13N5O4
InChI KeyInChIKey=IRSCQMHQWWYFCW-UHFFFAOYSA-N
InChI
InChI=1S/C9H13N5O4/c10-9-12-7-6(8(17)13-9)11-3-14(7)4-18-5(1-15)2-16/h3,5,15-16H,1-2,4H2,(H3,10,12,13,17)
IUPAC Name
2-amino-9-{[(1,3-dihydroxypropan-2-yl)oxy]methyl}-6,9-dihydro-1H-purin-6-one
SMILES
NC1=NC2=C(N=CN2COC(CO)CO)C(=O)N1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as hypoxanthines. These are compounds containing the purine derivative 1H-purin-6(9H)-one. Purine is a bicyclic aromatic compound made up of a pyrimidine ring fused to an imidazole ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassImidazopyrimidines
Sub ClassPurines and purine derivatives
Direct ParentHypoxanthines
Alternative Parents
Substituents
  • Hypoxanthine
  • 6-oxopurine
  • Glycerolipid
  • Glycerol ether
  • Pyrimidone
  • Pyrimidine
  • Primary aromatic amine
  • N-substituted imidazole
  • Saccharide
  • Heteroaromatic compound
  • Vinylogous amide
  • Imidazole
  • Azole
  • Lactam
  • Azacycle
  • Hydrocarbon derivative
  • Primary amine
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor induction and maintenance in the treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS). Also used in the treatment of severe cytomegalovirus (CMV) disease, including CMV pneumonia, CMV gastrointestinal disease, and disseminated CMV infections, in immunocompromised patients.
PharmacodynamicsGanciclovir is a synthetic nucleoside analogue of 2'-deoxyguanosine that inhibits replication of herpes viruses both in vitro and in vivo. Sensitive human viruses include cytomegalovirus (CMV), herpes simplex virus -1 and -2 (HSV-1, HSV-2), Epstein-Barr virus (EBV) and varicella zoster virus (VZV), however clinical studies have been limited to assessment of efficacy in patients with CMV infection. Ganciclovir is a prodrug that is structurally similar to acyclovir. It inhibits virus replication by its encorporation into viral DNA. This encorporation inhibits dATP and leads to defective DNA, ceasing or retarding the viral machinery required to spread the virus to other cells.
Mechanism of actionGanciclovir's antiviral activity inhibits virus replication. This inhibitory action is highly selective as the drug must be converted to the active form by a virus-encoded cellular enzyme, thymidine kinase (TK). TK catalyzes phosphorylation of ganciclovir to the monophosphate, which is then subsequently converted into the diphosphate by cellular guanylate kinase and into the triphosphate by a number of cellular enzymes. In vitro, ganciclovir triphosphate stops replication of herpes viral DNA. When used as a substrate for viral DNA polymerase, ganciclovir triphosphate competitively inhibits dATP leading to the formation of 'faulty' DNA. This is where 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
AbsorptionPoorly absorbed systemically following oral administration. Bioavailability under fasting conditions is approximately 5%, and when administered with food, 6 to 9% (about 30% with a fatty meal).
Volume of distribution
  • 0.74 ± 0.15 L/kg
Protein binding1 to 2%
Metabolism

Little to no metabolism, about 90% of plasma ganciclovir is eliminated unchanged in the urine.

Route of eliminationRenal excretion of unchanged drug by glomerular filtration and active tubular secretion is the major route of elimination of ganciclovir.
Half life2.5 to 3.6 hours (mean 2.9 hours) when administered intravenously in adults. 3.1 to 5.5 hours when administered orally in adults. Renal function impairment causes a marked increase in half life (9 to 30 hours intravenously, 15.7 to 18.2 hours orally).
Clearance
  • 128 +/- 63 mL/min [Patients with Renal Impairment (Clcr=50-79 mL/min)]
  • 57+/- 8 mL/min [Patients with Renal Impairment (Clcr=25-49 mL/min)]
  • 30 +/- 13 mL/min [Patients with Renal Impairment (Clcr<25 mL/min)]
  • 4.7+/- 2.2 mL/min/kg [pediatric patients, aged 9 months to 12 years]
ToxicityOral, mouse LD50: > 2g/kg. Intravenous, dog LD50: > 150mg/kg. Symptoms of overdose include irreversible pancytopenia, worsening GI symptoms, and acute renal failure. Suspected cancer agent.
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+0.9443
Blood Brain Barrier+0.9866
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.5767
P-glycoprotein inhibitor INon-inhibitor0.932
P-glycoprotein inhibitor IINon-inhibitor0.8381
Renal organic cation transporterNon-inhibitor0.8459
CYP450 2C9 substrateNon-substrate0.8907
CYP450 2D6 substrateNon-substrate0.8225
CYP450 3A4 substrateNon-substrate0.5919
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.96
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.935
Ames testNon AMES toxic0.6094
CarcinogenicityNon-carcinogens0.8875
BiodegradationNot ready biodegradable0.9368
Rat acute toxicity2.0348 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9611
hERG inhibition (predictor II)Non-inhibitor0.8943
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Roche palo alto llc
  • Ranbaxy laboratories ltd
  • Bausch and lomb inc
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
Packagers
Dosage forms
FormRouteStrength
Capsuleoral250 mg
Powder for solutionintravenous500 mg
Injection, powder, lyophilized, for solutionintravenous500 mg/10mL
Capsuleoral500 mg
Capsuleoral250 mg/1
Capsuleoral500 mg/1
Implantintravitreal4.5 mg
Gelophthalmic1.5 mg/g
Prices
Unit descriptionCostUnit
Vitrasert 4.5 mg implant19200.0USD implant
Cytovene 500 mg vial81.06USD vial
Cytovene 500 mg/vial46.41USD vial
Zirgan 0.15% ophthalmic gel33.6USD g
Ganciclovir 500 mg capsule19.66USD capsule
Cytovene 500 mg capsule10.99USD capsule
Cytovene 250 mg capsule5.61USD capsule
Ganciclovir 250 mg capsule4.72USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5378475 No1995-01-032012-01-03Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point250 dec °CPhysProp
water solubility4300 mg/L (at 25 °C)MERCK INDEX (1996); pH 7
logP-1.66SANGSTER (1993)
Caco2 permeability-6.27ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility11.5 mg/mLALOGPS
logP-1.8ALOGPS
logP-2.2ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)10.16ChemAxon
pKa (Strongest Basic)1.76ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area134.99 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity61.03 m3·mol-1ChemAxon
Polarizability24.15 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US4355032
General ReferencesNot Available
External Links
ATC CodesJ05AB06S01AD09
AHFS Codes
  • 08:18.32
PDB Entries
FDA labelDownload (489 KB)
MSDSDownload (119 KB)
Interactions
Drug Interactions
Drug
AbacavirThe risk or severity of adverse effects can be increased when Ganciclovir is combined with Abacavir.
Adefovir DipivoxilThe risk or severity of adverse effects can be increased when Ganciclovir is combined with Adefovir Dipivoxil.
CilastatinThe risk or severity of adverse effects can be increased when Ganciclovir is combined with Cilastatin.
DidanosineThe risk or severity of adverse effects can be increased when Ganciclovir is combined with Didanosine.
EmtricitabineThe risk or severity of adverse effects can be increased when Ganciclovir is combined with Emtricitabine.
EntecavirThe risk or severity of adverse effects can be increased when Ganciclovir is combined with Entecavir.
ImipenemThe risk or severity of adverse effects can be increased when Ganciclovir is combined with Imipenem.
LamivudineThe risk or severity of adverse effects can be increased when Ganciclovir is combined with Lamivudine.
Mycophenolate mofetilThe serum concentration of Ganciclovir can be increased when it is combined with Mycophenolate mofetil.
Mycophenolic acidThe serum concentration of Ganciclovir can be increased when it is combined with Mycophenolic acid.
ProbenecidThe serum concentration of Ganciclovir can be increased when it is combined with Probenecid.
TenofovirThe serum concentration of Tenofovir can be increased when it is combined with Ganciclovir.
ZidovudineThe risk or severity of adverse effects can be increased when Ganciclovir is combined with Zidovudine.
Food Interactions
  • Take with food, food increases bioavailability.

Targets

Kind
Protein
Organism
HHV-1
Pharmacological action
yes
Actions
inhibitor
General Function:
Rna-dna hybrid ribonuclease activity
Specific Function:
Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding protein. Additionally, the polymerase contains an intrinsic ribonuclease H (RNase H) activity that specifically degrades RNA/DNA heteroduplexes or duplex DNA substrates in the 5' to 3' direction. Therefo...
Gene Name:
Not Available
Uniprot ID:
P04293
Molecular Weight:
136419.66 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 ]
  3. 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 ]
  4. Wang JT, Yang PW, Lee CP, Han CH, Tsai CH, Chen MR: Detection of Epstein-Barr virus BGLF4 protein kinase in virus replication compartments and virus particles. J Gen Virol. 2005 Dec;86(Pt 12):3215-25. [PubMed:16298966 ]
  5. Shi R, Azzi A, Gilbert C, Boivin G, Lin SX: Three-dimensional modeling of cytomegalovirus DNA polymerase and preliminary analysis of drug resistance. Proteins. 2006 Aug 1;64(2):301-7. [PubMed:16705640 ]
2. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
incorporation into and destabilization
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 ]
Kind
Protein
Organism
HHV-1
Pharmacological action
yes
Actions
inducer
General Function:
Thymidine kinase activity
Specific Function:
In latent infection, may allow the virus to be reactivated and to grow in cells lacking a high concentration of phosphorylated nucleic acid precursors, such as nerve cells that do not replicate their genome.
Gene Name:
TK
Uniprot ID:
P03176
Molecular Weight:
40971.555 Da
References
  1. Champness JN, Bennett MS, Wien F, Visse R, Summers WC, Herdewijn P, de Clerq E, Ostrowski T, Jarvest RL, Sanderson MR: Exploring the active site of herpes simplex virus type-1 thymidine kinase by X-ray crystallography of complexes with aciclovir and other ligands. Proteins. 1998 Aug 15;32(3):350-61. [PubMed:9715911 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Secondary active organic cation transmembrane transporter activity
Specific Function:
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine...
Gene Name:
SLC22A1
Uniprot ID:
O15245
Molecular Weight:
61153.345 Da
References
  1. Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. [PubMed:11861798 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
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. Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. [PubMed:11861798 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
References
  1. Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. [PubMed:11861798 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha-ketoglutarate.
Gene Name:
SLC22A7
Uniprot ID:
Q9Y694
Molecular Weight:
60025.025 Da
References
  1. Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Endou H: Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24. [PubMed:11861798 ]
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Drug created on June 13, 2005 07:24 / Updated on April 11, 2014 14:45