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Identification
NameFoscarnet
Accession NumberDB00529  (APRD00669)
TypeSmall Molecule
GroupsApproved
Description

An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV. [PubChem]

Structure
Thumb
Synonyms
Carboxyphosphonic acid
Foscarmet
Phosphonoformate
Phosphonoformic acid
Phosphonomethanoic acid
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Foscavirinjection, solution24 mg/mLintravenousClinigen Healthcare Ltd.2012-07-09Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Foscarnet Sodiuminjection, solution24 mg/mLintravenousHospira, Inc.2010-07-07Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
TriaptenNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Foscarnet sodium
63585-09-1
Thumb
  • InChI Key: DFHAXXVZCFXGOQ-UHFFFAOYSA-K
  • Monoisotopic Mass: 191.917643647
  • Average Mass: 191.9508
DBSALT000200
Categories
UNII364P9RVW4X
CAS number4428-95-9
WeightAverage: 126.0053
Monoisotopic: 125.971809718
Chemical FormulaCH3O5P
InChI KeyInChIKey=ZJAOAACCNHFJAH-UHFFFAOYSA-N
InChI
InChI=1S/CH3O5P/c2-1(3)7(4,5)6/h(H,2,3)(H2,4,5,6)
IUPAC Name
phosphonoformic acid
SMILES
OC(=O)P(O)(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as organic phosphonic acids. These are organic compounds containing phosphonic acid.
KingdomOrganic compounds
Super ClassOrganophosphorus compounds
ClassOrganic phosphonic acids and derivatives
Sub ClassOrganic phosphonic acids
Direct ParentOrganic phosphonic acids
Alternative Parents
Substituents
  • Organophosphonic acid
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) and for treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients.
PharmacodynamicsFoscarnet is an organic analogue of inorganic pyrophosphate that inhibits replication of herpes viruses in vitro including cytomegalovirus (CMV) and herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). Foscarnet does not require activation (phosphorylation) by thymidine kinase or other kinases and therefore is active in vitro against HSV TK deficient mutants and CMV UL97 mutants. Thus, HSV strains resistant to acyclovir or CMV strains resistant to ganciclovir may be sensitive to foscarnet. However, acyclovir or ganciclovir resistant mutants with alterations in the viral DNA polymerase may be resistant to foscarnet and may not respond to therapy with foscarnet. The combination of foscarnet and ganciclovir has been shown to have enhanced activity in vitro.
Mechanism of actionFoscarnet exerts its antiviral activity by a selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases.
Related Articles
AbsorptionPoorly absorbed after oral administration (bioavailability from 12 to 22%).
Volume of distributionNot Available
Protein binding14-17%
Metabolism

Not metabolized.

Route of eliminationNot Available
Half life3.3-6.8 hours
Clearance
  • 2.13 +/- 0.71 mL/min/kg [patients had normal renal function (CrCl > 80 mL/min]
  • 68 +/- 8 mL/min/kg [CrCl was 50-80 mL/min]
  • 34 +/- 9 mL/min/kg [CrCl was 25-49 mL/min]
  • 20 +/- 4 mL/min/kg [CrCl was 10 – 24 mL/min]
ToxicityOral, rat LD50: >2,000 mg/kg. Signs of overdose include renal impairment.
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-0.9396
Blood Brain Barrier+0.9382
Caco-2 permeable-0.8957
P-glycoprotein substrateNon-substrate0.8162
P-glycoprotein inhibitor INon-inhibitor0.9783
P-glycoprotein inhibitor IINon-inhibitor0.9962
Renal organic cation transporterNon-inhibitor0.9731
CYP450 2C9 substrateNon-substrate0.8114
CYP450 2D6 substrateNon-substrate0.861
CYP450 3A4 substrateNon-substrate0.7282
CYP450 1A2 substrateNon-inhibitor0.8825
CYP450 2C9 inhibitorNon-inhibitor0.9124
CYP450 2D6 inhibitorNon-inhibitor0.9086
CYP450 2C19 inhibitorNon-inhibitor0.9202
CYP450 3A4 inhibitorNon-inhibitor0.9608
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.996
Ames testNon AMES toxic0.9139
CarcinogenicityNon-carcinogens0.5461
BiodegradationNot ready biodegradable0.5449
Rat acute toxicity1.7117 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9831
hERG inhibition (predictor II)Non-inhibitor0.96
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Hospira inc
  • Clinigen healthcare ltd
Packagers
Dosage forms
FormRouteStrength
Injection, solutionintravenous24 mg/mL
Prices
Unit descriptionCostUnit
Sodium phosphonoformate powder286.3USD g
Foscavir 24 mg/ml infus bottle0.43USD ml
Foscarnet 24 mg/ml infus bttl0.37USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point88.06 °CNot Available
water solubilityCompleteNot Available
logP-2.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility16.8 mg/mLALOGPS
logP-1.6ALOGPS
logP-0.83ChemAxon
logS-0.88ALOGPS
pKa (Strongest Acidic)-0.096ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area94.83 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity19.07 m3·mol-1ChemAxon
Polarizability7.89 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Charles E. McKenna, “Preparation and use of thiophosphonates and thio-analogues of phosphonoformic acid.” U.S. Patent US5072032, issued February, 1953.

US5072032
General ReferencesNot Available
External Links
ATC CodesJ05AD01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (101 KB)
MSDSDownload (50.2 KB)
Interactions
Drug Interactions
Drug
AciclovirFoscarnet may increase the nephrotoxic activities of Aciclovir.
AmikacinFoscarnet may increase the nephrotoxic activities of Amikacin.
Amphotericin BFoscarnet may increase the nephrotoxic activities of Amphotericin B.
ArbekacinFoscarnet may increase the nephrotoxic activities of Arbekacin.
BumetanideThe serum concentration of Foscarnet can be increased when it is combined with Bumetanide.
CitalopramFoscarnet may increase the QTc-prolonging activities of Citalopram.
CyclosporineFoscarnet may increase the nephrotoxic activities of Cyclosporine.
DofetilideFoscarnet may increase the QTc-prolonging activities of Dofetilide.
Etacrynic acidThe serum concentration of Foscarnet can be increased when it is combined with Ethacrynic acid.
FramycetinFoscarnet may increase the nephrotoxic activities of Framycetin.
FurosemideThe serum concentration of Foscarnet can be increased when it is combined with Furosemide.
GentamicinFoscarnet may increase the nephrotoxic activities of Gentamicin.
GoserelinFoscarnet may increase the QTc-prolonging activities of Goserelin.
KanamycinFoscarnet may increase the nephrotoxic activities of Kanamycin.
LeuprolideFoscarnet may increase the QTc-prolonging activities of Leuprolide.
MethotrexateFoscarnet may increase the nephrotoxic activities of Methotrexate.
MifepristoneMifepristone may increase the QTc-prolonging activities of Foscarnet.
NeomycinFoscarnet may increase the nephrotoxic activities of Neomycin.
NetilmicinFoscarnet may increase the nephrotoxic activities of Netilmicin.
PentamidineThe risk or severity of adverse effects can be increased when Pentamidine is combined with Foscarnet.
RibostamycinFoscarnet may increase the nephrotoxic activities of Ribostamycin.
SpectinomycinFoscarnet may increase the nephrotoxic activities of Spectinomycin.
StreptomycinFoscarnet may increase the nephrotoxic activities of Streptomycin.
TacrolimusFoscarnet may increase the nephrotoxic activities of Tacrolimus.
TobramycinFoscarnet may increase the nephrotoxic activities of Tobramycin.
TorasemideThe serum concentration of Foscarnet can be increased when it is combined with Torasemide.
ValaciclovirFoscarnet may increase the nephrotoxic activities of Valaciclovir.
Food InteractionsNot Available

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. Ducancelle A, Alain S, Petit F, Sanson Le Pors MJ, Mazeron MC: Development and validation of a non-radioactive DNA polymerase assay for studying cytomegalovirus resistance to foscarnet. J Virol Methods. 2007 May;141(2):212-5. Epub 2007 Jan 2. [PubMed:17197042 ]
  4. Bonnafous P, Naesens L, Petrella S, Gautheret-Dejean A, Boutolleau D, Sougakoff W, Agut H: Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet. Antivir Ther. 2007;12(6):877-88. [PubMed:17926642 ]
  5. Tchesnokov EP, Gilbert C, Boivin G, Gotte M: Role of helix P of the human cytomegalovirus DNA polymerase in resistance and hypersusceptibility to the antiviral drug foscarnet. J Virol. 2006 Feb;80(3):1440-50. [PubMed:16415021 ]
Kind
Protein
Organism
HHV-5
Pharmacological action
yes
Actions
inhibitor
General Function:
Nucleotide binding
Specific Function:
Replicates viral genomic DNA in the late phase of lytic infection, producing long concatemeric DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding protein (By similarity).
Gene Name:
UL54
Uniprot ID:
P08546
Molecular Weight:
137100.705 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. Ducancelle A, Alain S, Petit F, Sanson Le Pors MJ, Mazeron MC: Development and validation of a non-radioactive DNA polymerase assay for studying cytomegalovirus resistance to foscarnet. J Virol Methods. 2007 May;141(2):212-5. Epub 2007 Jan 2. [PubMed:17197042 ]
  4. Bonnafous P, Naesens L, Petrella S, Gautheret-Dejean A, Boutolleau D, Sougakoff W, Agut H: Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet. Antivir Ther. 2007;12(6):877-88. [PubMed:17926642 ]
  5. Tchesnokov EP, Gilbert C, Boivin G, Gotte M: Role of helix P of the human cytomegalovirus DNA polymerase in resistance and hypersusceptibility to the antiviral drug foscarnet. J Virol. 2006 Feb;80(3):1440-50. [PubMed:16415021 ]

Transporters

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. Wada S, Tsuda M, Sekine T, Cha SH, Kimura M, Kanai Y, Endou H: Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs. J Pharmacol Exp Ther. 2000 Sep;294(3):844-9. [PubMed:10945832 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Symporter activity
Specific Function:
Proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate. Depending on the tissue and on cicumstances, mediates the import or export of lactic acid and ketone bod...
Gene Name:
SLC16A1
Uniprot ID:
P53985
Molecular Weight:
53943.685 Da
References
  1. Tamai I, Sai Y, Ono A, Kido Y, Yabuuchi H, Takanaga H, Satoh E, Ogihara T, Amano O, Izeki S, Tsuji A: Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1. J Pharm Pharmacol. 1999 Oct;51(10):1113-21. [PubMed:10579682 ]
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Drug created on June 13, 2005 07:24 / Updated on April 29, 2016 09:37