Foscarnet

Foscarnet
Clinical data
Trade names Foscavir
AHFS/Drugs.com Monograph
MedlinePlus a601144
Pregnancy
category
Routes of
administration
Intravenous
ATC code J05AD01 (WHO)
Legal status
Legal status
  • ℞-only (U.S.), POM (UK)
Pharmacokinetic data
Bioavailability NA
Protein binding 14-17%
Biological half-life 3.3-6.8 hours
Identifiers
Synonyms phosphonomethanoic acid, dihydroxyphosphinecarboxylic acid oxide
CAS Number 4428-95-9 N (trisodium salt)
PubChem (CID) 3415
IUPHAR/BPS 5497
DrugBank DB00529 YesY
ChemSpider 3297 YesY
UNII 364P9RVW4X N
KEGG C06456 YesY
ChEBI CHEBI:127780 YesY
ChEMBL CHEMBL666 YesY
ECHA InfoCard 100.224.300
Chemical and physical data
Formula CH3O5P
Molar mass 126.005 g/mol
300.1 g/mol (foscarnet trisodium hexahydrate)
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

Foscarnet is the conjugate base of the chemical compound with the formula HO2CPO3H2. Foscarnet sodium is used as an antiviral medication.

Foscarnet was approved for medical use in 1991.[1]

Medical use

This phosphonic acid derivative (marketed by Clinigen as foscarnet sodium under the trade name Foscavir) is an antiviral medication used to treat herpes viruses, including drug-resistant cytomegalovirus (CMV) and herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2). It is particularly used to treat CMV retinitis. Foscarnet can be used to treat highly treatment-experienced patients with HIV as part of salvage therapy.[2][3][4]

Mechanism of action

Foscarnet is a structural mimic of the anion pyrophosphate[5] that selectively inhibits the pyrophosphate binding site on viral DNA polymerases at concentrations that do not affect human DNA polymerases.

In individuals treated with the DNA polymerase inhibitors acyclovir or ganciclovir, HSV or CMV particles can develop mutant protein kinases (thymidine kinase or UL97 protein kinase, respectively) that make them resistant to these antiviral drugs. However, unlike acyclovir and ganciclovir, foscarnet is not activated by viral protein kinases, making it useful in acyclovir- or ganciclovir-resistant HSV and CMV infections.

However, acyclovir- or ganciclovir-resistant mutants with alterations in viral DNA polymerase may also be resistant to foscarnet.[6][7]

Administration

Intravenous infusion or intravitreous injection.

Side effects

References

  1. Long, Sarah S.; Pickering, Larry K.; Prober, Charles G. (2012). Principles and Practice of Pediatric Infectious Disease. Elsevier Health Sciences. p. 1502. ISBN 1437727026.
  2. Canestri A, Ghosn J, Wirden M, et al. (2006). "Foscarnet salvage therapy for patients with late-stage HIV disease and multiple drug resistance". Antivir. Ther. (Lond.). 11 (5): 561–6. PMID 16964823.
  3. Mathiesen S, Dam E, Roge B, et al. (2007). "Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1". Antivir. Ther. (Lond.). 12 (3): 335–43. PMID 17591023.
  4. Meyer PR, Rutvisuttinunt W, Matsuura SE, So AG, Scott WA (2007). "Stable complexes formed by HIV-1 reverse transcriptase at distinct positions on the primer-template controlled by binding deoxynucleoside triphosphates or foscarnet". J. Mol. Biol. 369 (1): 41–54. doi:10.1016/j.jmb.2007.03.006. PMC 1986715Freely accessible. PMID 17400246.
  5. Meyer PR, Rutvisuttinunt W, Matsuura SE, So AG, Scott WA (May 2007). "Stable complexes formed by HIV-1 reverse transcriptase at distinct positions on the primer-template controlled by binding deoxynucleoside triphosphates or foscarnet". J. Mol. Biol. 369 (1): 41–54. doi:10.1016/j.jmb.2007.03.006. PMC 1986715Freely accessible. PMID 17400246.
  6. Bonnafous P, Naesens L, Petrella S, et al. (2007). "Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet". Antivir. Ther. (Lond.). 12 (6): 877–88. PMID 17926642.
  7. Tchesnokov EP, Gilbert C, Boivin G, Götte M (February 2006). "Role of helix P of the human cytomegalovirus DNA polymerase in resistance and hypersusceptibility to the antiviral drug foscarnet". J. Virol. 80 (3): 1440–50. doi:10.1128/JVI.80.3.1440-1450.2006. PMC 1346920Freely accessible. PMID 16415021.
  • Harrison Tectbook of Medicine 16th ed, page 2244
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