Identification

Name
Ganciclovir
Accession Number
DB01004  (APRD00263, EXPT01540)
Type
Small Molecule
Groups
Approved, 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 IDs
BW 759U / BW-759U / RS-21592
Product Ingredients
IngredientUNIICASInChI Key
Ganciclovir Sodium02L083W284107910-75-8JJICLMJFIKGAAU-UHFFFAOYSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CytovenePowder, for solution500 mgIntravenousHoffmann La Roche1995-12-31Not applicableCanada
Cytovene - Cap 250mgCapsule250 mgOralHoffmann La Roche1995-12-312007-08-02Canada
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 Roche2000-01-142007-08-02Canada
GanciclovirInjection, solution2 mg/1mLIntravenousExela Pharma Sciences, Llc.2017-02-28Not applicableUs
GanciclovirInjection, powder, lyophilized, for solution500 mg/10mLIntravenousMylan Laboratories Limited2017-12-31Not applicableUs
Ganciclovir for InjectionPowder, for solution500 mgIntravenousFresenius Kabi2014-04-08Not applicableCanada
Ganciclovir for Injection USPPowder, for solution500 mgIntravenousAuro Pharma IncNot applicableNot applicableCanada
VitrasertImplant4.5 mg/1IntravitrealBauch & Lomb Incorporated1996-03-042012-09-04Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
GanciclovirCapsule250 mg/1OralRanbaxy Inc.2003-08-27Not applicableUs
GanciclovirInjection, powder, lyophilized, for solution500 mg/10mLIntravenousFresenius Kabi USA, LLC2010-06-28Not applicableUs
GanciclovirInjection, powder, lyophilized, for solution50 mg/1mLIntravenousBedford Pharmaceuticals2010-12-302010-12-31Us
GanciclovirInjection, powder, lyophilized, for solution500 mg/10mLIntravenousPar Pharmaceutical, Inc.2016-12-06Not applicableUs
GanciclovirInjection, solution50 mg/1mLIntravenousSagent Pharmaceuticals2018-02-15Not applicableUs
GanciclovirCapsule500 mg/1OralRanbaxy Inc.2003-08-27Not applicableUs
GanciclovirGel1.5 mg/1gOphthalmicAmici Pharmaceuticals Llc2017-09-08Not applicableUs
GanciclovirInjection, solution500 mg/10mLIntravenousPharmascience Inc.2018-04-24Not applicableUs
International/Other Brands
Cytovene / Vitrasert
Categories
UNII
P9G3CKZ4P5
CAS number
82410-32-0
Weight
Average: 255.2306
Monoisotopic: 255.096753929
Chemical Formula
C9H13N5O4
InChI Key
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

Pharmacology

Indication

For 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.

Associated Conditions
Pharmacodynamics

Ganciclovir 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 action

Ganciclovir'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.

TargetActionsOrganism
ADNA polymerase catalytic subunit
inhibitor
HHV-1
ADNA
incorporation into and destabilization
Human
AThymidine kinase
inducer
HHV-1
Absorption

Poorly 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 binding

1 to 2%

Metabolism

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

Route of elimination

Renal excretion of unchanged drug by glomerular filtration and active tubular secretion is the major route of elimination of ganciclovir.

Half life

2.5 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]
Toxicity

Oral, 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
7-NitroindazoleThe therapeutic efficacy of 7-Nitroindazole can be decreased when used in combination with Ganciclovir.
AbacavirThe risk or severity of cytopenia can be increased when Ganciclovir is combined with Abacavir.
AbemaciclibThe excretion of Abemaciclib can be decreased when combined with Ganciclovir.
AcarboseAcarbose may decrease the excretion rate of Ganciclovir which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Ganciclovir which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Ganciclovir which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Ganciclovir which could result in a higher serum level.
AcetazolamideThe therapeutic efficacy of Acetazolamide can be decreased when used in combination with Ganciclovir.
AcetylcholineThe risk or severity of adverse effects can be increased when Ganciclovir is combined with Acetylcholine.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Ganciclovir which could result in a higher serum level.
Food Interactions
  • Take with food, food increases bioavailability.

References

Synthesis Reference
US4355032
General References
Not Available
External Links
Human Metabolome Database
HMDB0015139
KEGG Drug
D00333
PubChem Compound
3454
PubChem Substance
46507294
ChemSpider
3336
BindingDB
85707
ChEBI
465284
ChEMBL
CHEMBL182
Therapeutic Targets Database
DAP000645
PharmGKB
PA449733
HET
GA2
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ganciclovir
ATC Codes
J05AB06 — GanciclovirS01AD09 — Ganciclovir
AHFS Codes
  • 08:18.32 — Nucleosides and Nucleotides
PDB Entries
1ki2 / 4da6
FDA label
Download (489 KB)
MSDS
Download (119 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentBrain and Central Nervous System Tumors1
1CompletedTreatmentCancer of the Ovary1
1CompletedTreatmentColitis / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentCytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections4
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Infections, Cytomegalovirus2
1CompletedTreatmentLeukemias / Malignant Lymphomas / Precancerous Conditions / Small Intestine Cancer1
1CompletedTreatmentMelanoma (Skin)1
1CompletedTreatmentNeoplasms Metastasis / Neoplasms, Brain1
1CompletedTreatmentNeuroblastomas1
1RecruitingTreatmentTransplantation, Liver1
1TerminatedTreatmentLymphoproliferative Disorders / Malignant Lymphomas1
1Unknown StatusTreatmentMesothelioma, Malignant1
1WithdrawnTreatmentEncephalopathies / Human Immunodeficiency Virus (HIV) Infections / Radiculitis1
1, 2CompletedTreatmentInfections, Cytomegalovirus1
1, 2CompletedTreatmentKidney Diseases / Transplant, Kidney / Transplantation, Kidney / Transplantation, Renal1
2CompletedPreventionAcute Lung Injury (ALI) / Acute Respiratory Distress Syndrome (ARDS) / Respiratory Failure1
2CompletedPreventionCritical Illness1
2CompletedSupportive CareChronic Myeloproliferative Disorders / Leukemias / Malignant Lymphomas / Multiple Myeloma (MM) / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Diseases / Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable / Smith-Magenis Syndrome1
2CompletedTreatmentCytomegalovirus Retinitis / Gastrointestinal Diseases / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentCytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections3
2CompletedTreatmentDiabetes Mellitus, Insulin-Dependent1
2CompletedTreatmentHepatocellular,Carcinoma / Liver Cancer1
2CompletedTreatmentMalignant Lymphomas2
2RecruitingTreatmentHerpes Zoster Keratitis1
2TerminatedTreatmentEBV Lymphomas / Lympho-proliferative Diseases1
2Unknown StatusSupportive CareGraft Versus Host Disease (GVHD) / Nonneoplastic Condition1
2Unknown StatusTreatmentCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer1
2, 3Not Yet RecruitingTreatmentCytomegalovirus Anterior Uveitis1
3CompletedPreventionInfections, Cytomegalovirus1
3CompletedSupportive CareInfection NOS1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Cytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentCytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections5
3CompletedTreatmentInfections, Cytomegalovirus2
3Not Yet RecruitingPreventionVirus Infection in Subjects Underwent Lung Transplantation1
3RecruitingNot AvailableRenal Transplant Recipient Patients1
3RecruitingTreatmentCytomegalovirus (CMV)1
3TerminatedPreventionAllogeneic Stem Cell Transplantation1
3TerminatedTreatmentInfections, Cytomegalovirus1
3Unknown StatusTreatmentAdenovirus / Conjunctivitis1
4CompletedPreventionDNA Virus Infections / Infections, Cytomegalovirus / Infections, Herpesviridae1
4CompletedTreatmentCytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentInfections, Cytomegalovirus2
4CompletedTreatmentKeratoconjunctivitis Due to Adenovirus / Viral Shedding1
4CompletedTreatmentViral sepsis1
4RecruitingTreatmentHematological Diseases / Infections, Cytomegalovirus1
4RecruitingTreatmentViral Pneumonia1
Not AvailableCompletedSupportive CareAccelerated Phase Chronic Myelogenous Leukemia / Acute Undifferentiated Leukemia (AUL) / Adult Acute Lymphoblastic Leukemia in Remission / Adult Acute Myeloid Leukemia in Remission / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Grade III Lymphomatoid Granulomatosis / Adult Nasal Type Extranodal NK/T-Cell Lymphoma / Anaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Aplastic Anaemia (AA) / Atypical Chronic Myeloid Leukemia, BCR-ABL Negative / Blastic Phase Chronic Myelogenous Leukemia / Chronic Eosinophilic Leukemia (CEL) / Chronic Lymphocytic Leukemia (CLL) - Refractory / Chronic Myelomonocytic Leukemia / Chronic Neutrophilic Leukemia / Chronic Phase Chronic Myelogenous Leukemia / Contiguous Stage II Adult Burkitt Lymphoma / Contiguous Stage II Adult Diffuse Large Cell Lymphoma / Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma / Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma / Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma / Contiguous Stage II Adult Lymphoblastic Lymphoma / Contiguous Stage II Grade 1 Follicular Lymphoma / Contiguous Stage II Grade 2 Follicular Lymphoma / Contiguous Stage II Grade 3 Follicular Lymphoma / Contiguous Stage II Mantle Cell Lymphoma / Contiguous Stage II Marginal Zone Lymphoma / Contiguous Stage II Small Lymphocytic Lymphoma / Cutaneous B-Cell Non-Hodgkin Lymphoma / De Novo Myelodysplastic Syndromes / Essential Thrombocythemia (ET) / Extramedullary Plasmacytoma / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Hematopoietic/Lymphoid Cancer / Infections, Cytomegalovirus / Intraocular Lymphoma / Isolated Plasmacytoma of Bone / Leukemia, Prolymphocytic / Malignant mast cell neoplasm / Meningeal Chronic Myelogenous Leukemia / Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable / Nodal marginal zone B-cell lymphomas / Noncontiguous Stage II Adult Burkitt Lymphoma / Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma / Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma / Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma / Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma / Noncontiguous Stage II Adult Lymphoblastic Lymphoma / Noncontiguous Stage II Grade 1 Follicular Lymphoma / Noncontiguous Stage II Grade 2 Follicular Lymphoma / Noncontiguous Stage II Grade 3 Follicular Lymphoma / Noncontiguous Stage II Mantle Cell Lymphoma / Noncontiguous Stage II Marginal Zone Lymphoma / Noncontiguous Stage II Small Lymphocytic Lymphoma / Polycythemia Vera (PV) / Post Transplant Lymphoproliferative Disorder / Previously Treated Myelodysplastic Syndromes / Primary Myelofibrosis / Primary Systemic Amyloidosis / Progressive Hairy Cell Leukemia, Initial Treatment / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Immunoblastic Large Cell Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / Recurrent Small Lymphocytic Lymphoma / Refractory Hairy Cell Leukemia / Refractory Multiple Myeloma / Relapsing Chronic Myelogenous Leukemia / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Secondary Myelodysplastic Syndromes / Secondary Myelofibrosis / Splenic Marginal Zone Lymphoma / Stage 0 Chronic Lymphocytic Leukemia / Stage I Adult Burkitt Lymphoma / Stage I Adult Diffuse Large Cell Lymphoma / Stage I Adult Diffuse Mixed Cell Lymphoma / Stage I Adult Diffuse Small Cleaved Cell Lymphoma / Stage I Adult Hodgkin Lymphoma / Stage I Adult Immunoblastic Large Cell Lymphoma / Stage I Adult Lymphoblastic Lymphoma / Stage I Adult T-Cell Leukemia/Lymphoma / Stage I Chronic Lymphocytic Leukemia / Stage I Cutaneous T-cell Non-Hodgkin Lymphoma / Stage I Grade 1 Follicular Lymphoma / Stage I Grade 2 Follicular Lymphoma / Stage I Grade 3 Follicular Lymphoma / Stage I Mantle Cell Lymphoma / Stage I Marginal Zone Lymphoma / Stage I Multiple Myeloma / Stage I Mycosis Fungoides/Sezary Syndrome / Stage I Small Lymphocytic Lymphoma / Stage II Adult Hodgkin Lymphoma / Stage II Adult T-Cell Leukemia/Lymphoma / Stage II Chronic Lymphocytic Leukemia / Stage II Cutaneous T-cell Non-Hodgkin Lymphoma / Stage II Multiple Myeloma / Stage II Mycosis Fungoides/Sezary Syndrome / Stage III Adult Burkitt Lymphoma / Stage III Adult Diffuse Large Cell Lymphoma / Stage III Adult Diffuse Mixed Cell Lymphoma / Stage III Adult Diffuse Small Cleaved Cell Lymphoma / Stage III Adult Hodgkin Lymphoma / Stage III Adult Immunoblastic Large Cell Lymphoma / Stage III Adult Lymphoblastic Lymphoma / Stage III Adult T-Cell Leukemia/Lymphoma / Stage III Chronic Lymphocytic Leukemia / Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage III Grade 1 Follicular Lymphoma / Stage III Grade 2 Follicular Lymphoma / Stage III Grade 3 Follicular Lymphoma / Stage III Mantle Cell Lymphoma / Stage III Marginal Zone Lymphoma / Stage III Multiple Myeloma / Stage III Mycosis Fungoides/Sezary Syndrome / Stage III Small Lymphocytic Lymphoma / Stage IV Adult Burkitt Lymphoma / Stage IV Adult Diffuse Large Cell Lymphoma / Stage IV Adult Diffuse Mixed Cell Lymphoma / Stage IV Adult Diffuse Small Cleaved Cell Lymphoma / Stage IV Adult Hodgkin Lymphoma / Stage IV Adult Immunoblastic Large Cell Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Stage IV Adult T-Cell Leukemia/Lymphoma / Stage IV Chronic Lymphocytic Leukemia / Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IV Grade 1 Follicular Lymphoma / Stage IV Grade 2 Follicular Lymphoma / Stage IV Grade 3 Follicular Lymphoma / Stage IV Mantle Cell Lymphoma / Stage IV Marginal Zone Lymphoma / Stage IV Mycosis Fungoides/Sezary Syndrome / Stage IV Small Lymphocytic Lymphoma / T-Cell Large Granular Lymphocyte Leukemia / Waldenström's Macroglobulinemia (WM)1
Not AvailableCompletedSupportive CareChronic Myeloproliferative Disorders / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms / Nonneoplastic Condition1
Not AvailableCompletedTreatmentAdenoviridae Infections / Conjunctivitis, Viral1
Not AvailableCompletedTreatmentAnterior Uveitis (AU) / Cytomegalovirus Anterior Segment Infection / Endotheliitis1
Not AvailableCompletedTreatmentColitis / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentCytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections11
Not AvailableCompletedTreatmentCytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections / Infections, Cytomegalovirus1
Not AvailableCompletedTreatmentEnd-Stage Renal Disease (ESRD)1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Infections, Cytomegalovirus4
Not AvailableCompletedTreatmentDiffuse posterior uveitis / Viral Infections1
Not AvailableRecruitingNot AvailableChildren; Infection / Newborn; Infection1
Not AvailableRecruitingNot AvailableInfections, Cytomegalovirus1
Not AvailableRecruitingTreatmentPrimary keratoconjunctivitis caused by herpes simplex virus type 21
Not AvailableUnknown StatusDiagnosticInfections, Cytomegalovirus1

Pharmacoeconomics

Manufacturers
  • Roche palo alto llc
  • Ranbaxy laboratories ltd
  • Bausch and lomb inc
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
Packagers
  • Alliance Medical Products
  • APP Pharmaceuticals
  • Bausch & Lomb Inc.
  • Bedford Labs
  • F Hoffmann La Roche Ltd.
  • F Hoffmann-La Roche Ltd.
  • JHP Pharmaceuticals LLC
  • Physicians Total Care Inc.
  • Ranbaxy Laboratories
  • Sirion Therapeutics
Dosage forms
FormRouteStrength
CapsuleOral250 mg
Powder, for solutionIntravenous500 mg
CapsuleOral500 mg
CapsuleOral250 mg/1
CapsuleOral500 mg/1
Injection, powder, lyophilized, for solutionIntravenous50 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous500 mg/10mL
Injection, solutionIntravenous2 mg/1mL
Injection, solutionIntravenous50 mg/1mL
Injection, solutionIntravenous500 mg/10mL
ImplantIntravitreal4.5 mg/1
ImplantIntravitreal4.5 mg
GelOphthalmic1.5 mg/1g
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)
US5378475No1995-01-032012-01-03Us
US9486530No2016-11-082034-09-02Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)250 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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

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-QQ , negativeLC-MS/MSsplash10-0gb9-0090000000-b4bf1558f31e6cd80503
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-014i-1090000000-80a7b4d22e1375eb8a4d
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-000j-9610000000-c3053bd735d9f92930bf
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-007a-9300000000-392c976e03c2a82984cc
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-00di-9000000000-168468ed262e2df62267
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4r-0490000000-0a16ac79577fd707fd15
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0udi-0920000000-16d50b83e7be32f4db70
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0udi-1900000000-2eca31ed3c60988970dc
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0udu-2900000000-fd85740333fbb29714c8
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-01pc-3900000000-81b422bf6764161bcb0f
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-0udi-0900000000-618946bbba03bdf5db19

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Imidazopyrimidines
Sub Class
Purines and purine derivatives
Direct Parent
Hypoxanthines
Alternative Parents
6-oxopurines / Pyrimidones / Glycerolipids / Aminopyrimidines and derivatives / N-substituted imidazoles / Vinylogous amides / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Primary alcohols
show 3 more
Substituents
6-oxopurine / Hypoxanthine / Aminopyrimidine / Pyrimidone / Glycerolipid / N-substituted imidazole / Pyrimidine / Azole / Imidazole / Heteroaromatic compound
show 14 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
oxopurine, 2-aminopurines (CHEBI:465284)

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 pro...
Gene Name
Not Available
Uniprot ID
P04293
Uniprot Name
DNA polymerase catalytic subunit
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 the...
Gene Name
TK
Uniprot ID
P03176
Uniprot Name
Thymidine kinase
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
Substrate
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-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
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]
  2. Wagner DJ, Hu T, Wang J: Polyspecific organic cation transporters and their impact on drug intracellular levels and pharmacodynamics. Pharmacol Res. 2016 Sep;111:237-246. doi: 10.1016/j.phrs.2016.06.002. Epub 2016 Jun 16. [PubMed:27317943]
  3. Shugarts S, Benet LZ: The role of transporters in the pharmacokinetics of orally administered drugs. Pharm Res. 2009 Sep;26(9):2039-54. doi: 10.1007/s11095-009-9924-0. Epub 2009 Jun 30. [PubMed:19568696]
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 ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
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, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
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 sulf...
Gene Name
SLC22A7
Uniprot ID
Q9Y694
Uniprot Name
Solute carrier family 22 member 7
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K: Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71. doi: 10.1016/j.bcp.2007.04.010. Epub 2007 Apr 13. [PubMed:17509534]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Drug transmembrane transporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K: Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71. doi: 10.1016/j.bcp.2007.04.010. Epub 2007 Apr 13. [PubMed:17509534]
  2. Nies AT, Damme K, Schaeffeler E, Schwab M: Multidrug and toxin extrusion proteins as transporters of antimicrobial drugs. Expert Opin Drug Metab Toxicol. 2012 Dec;8(12):1565-77. doi: 10.1517/17425255.2012.722996. Epub 2012 Sep 13. [PubMed:22970772]

Drug created on June 13, 2005 07:24 / Updated on December 12, 2018 13:12