63585-09-1 Usage
Description
Foscamet sodium is a new, injectable antiviral agent useful in the treatment of severe
cytomegalovirus retinitis in immunodepressed patients. Foscarnet sodium acts by
inhibiting viral-specific DNA polymerases; its side-effects include decreased hemoglobin
levels and acute tubular necrosis.
Originator
Astra (Sweden)
Uses
Inhibits viral DNA polymerase and reverse transcriptase.
Foscarnet is the only antiviral approved by the FDA for the treatment of acyclovir-resistant HSV infections, a growing problem in the AIDS population. Foscarnet does not require HSV-encoded thymidine kinase. Foscarnet therapy reduces the healing time, pain, and viral shedding. It is administered intravenously, 40 mg/kg every 8 to 12 hours within 7 to 10 days in patients suspected of having acyclovir-resistant herpes simplex infection. Foscarnet is administered for 10 days. Associated side effects include azotemia secondary to nephrotoxicity, hyperphosphatemia, hypocalcemia, anemia, nausea, vomiting, and genital ulceration. Patients may eventually develop resistant strains. Preliminary trials indicate that topical 1%foscarnet cream may have some benefit for the treatment of acyclovir-resistant mucocutaneous HSV infection in patients with AIDS.
Definition
ChEBI: The trisodium salt of phosphonoformic acid. It is used as an antiviral agent in the treatment of cytomegalovirus retinitis (CMV retinitis, an inflamation of the retina that can lead to blindness) and as an alternative to ganciclovir for AIDS patients who r
quire concurrent antiretroviral therapy but are unable to tolerate ganciclovir due to haematological toxicity.
Brand name
Foscavir (AstraZeneca).
Therapeutic Function
Antiviral
General Description
pyrophosphateanalog that inhibits replication in herpesviruses(CMV, HSV, and VSV) and retroviruses (HIV).Foscarnet(Foscavir) is taken up slowly by the cells and does not undergosignificant intracellular metabolism. Foscarnet is a reversible,noncompetitive inhibitor at the pyrophosphatebindingsite of the viral DNA polymerase and RT. Theultimate effect is inhibition of the cleavage of pyrophosphatefrom deoxynucleotide triphosphates and a cessation ofthe incorporation of nucleoside triphosphates into DNA(with the concomitant release of pyrophosphate).Becausethe inhibition is noncompetitive with respect to nucleosidetriphosphate binding, foscarnet can act synergistically withnucleoside triphosphate antimetabolites (e.g., zidovudineand didanosine triphosphates) in the inhibition of viral DNAsynthesis. Foscarnet does not require bioactivation by viralor cellular enzymes and, hence, can be effective against resistantviral strains that are deficient in virally encoded nucleosidekinases. Foscarnet is a second-line drug for the treatment of retinitiscaused by CMV in patients with AIDS. The drug causesmetabolic abnormalities including increases or decreases inblood Ca2 levels. Nephrotoxicity is common, and this sideeffect precludes the use of foscarnet in other infections causedby herpesvirus or as single-agent therapy for HIV infection.Foscarnet is an excellent ligand for metal ion binding,which undoubtedly contributes to the electrolyte imbalancesobserved with the use of the drug.Hypocalcemia, hypomagnesemia,hypokalemia, and hypophosphatemia and hyperphosphatemiaare observed in patients treated with foscarnet.Side effects such as paresthesias, tetani, seizures, and cardiacarrhythmias may result.
Clinical Use
Foscarnet sodium was approved by the U.S. FDA for the treatment of CMV retinitis in patients with AIDS.
In combination with ganciclovir, the results have been promising, even in progressive disease with
ganciclovir-resistant strains. Foscarnet sodium also is effective in the treatment of mucocutaneous
diseases caused by acyclovir-resistant strains of HSV and VZV in patients with AIDS. Foscarnet sodium
is administered IV at 60 mg/kg three times a day for initial therapy and at 90 to 120 mg/kg daily for
maintenance therapy. The plasma-half life is 3 to 6 hours. Foscarnet sodium penetrates into
the CSF and the eye. The drug is neurotoxic, and common adverse effects include phlebitis, anemia,
nausea, vomiting, and seizures. Foscarnet sodium carries the risk of severe hypocalcemia, especially
with concurrent use of IV pentamidine. Foscarnet sodium used with zidovudine (ZDV) has an additive
effect against CMV and acts synergistically against HIV.
Drug interactions
Potentially hazardous interactions with other drugs
Ciclosporin: may cause acute renal failure in
combination. Pentamidine: increased risk of hypocalcaemia with
parenteral pentamidine
Metabolism
There is no metabolic conversion of foscarnet and it is
eliminated by the kidneys as unchanged drug mainly
through glomerular filtration, with some active tubular
secretion.
Check Digit Verification of cas no
The CAS Registry Mumber 63585-09-1 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,3,5,8 and 5 respectively; the second part has 2 digits, 0 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 63585-09:
(7*6)+(6*3)+(5*5)+(4*8)+(3*5)+(2*0)+(1*9)=141
141 % 10 = 1
So 63585-09-1 is a valid CAS Registry Number.
InChI:InChI=1/CH3O5P.3Na/c2-1(3)7(4,5)6;;;/h(H,2,3)(H2,4,5,6);;;/q;3*+1/p-3
63585-09-1Relevant articles and documents
Acyloxymethyl and 4-acyloxybenzyl diester prodrugs of phosphonoformate
Briggs, Andrew D.,Camplo, Michel,Freeman, Sally,Lundstroem, Jan,Pring, Brian G.
, p. 14937 - 14950 (2007/10/03)
Sodium pivaloyloxymethyl (pivaloyloxymethoxycarbonyl)phosphonate 4, sodium 4-acyloxybenzyl phenoxycarbonylphosphonates 14a-c and sodium 4-acyloxybenzyl benzyloxycarbonylphosphonates 15a,b have been prepared as bioreversible prodrugs of the antiviral phosphonoformate 1. Their hydrolyses, in vivo systemic bioavailability and antiviral activity are reported. Of the compounds evaluated 4 was the best prodrug.
Method for combating virus infection
-
, (2008/06/13)
A method for the selective treatment of virus infections in animals and man comprising administering to a host so infected a therapeutically effective amount of phosphonoformic acid or a physiologically acceptable salt thereof.
Synthesis of esters of phosphonoformic acid and their antiherpes activity
Noren,Helgstrand,Johansson,Misiorny,Stening
, p. 264 - 270 (2007/10/02)
Aliphatic and aromatic mono-, di-, and triesters of phosphonoformic (foscarnet) were synthesized. The triesters were prepared by the Michaelis-Arbuzov reaction and were hydrolyzed to di- and monoesters. The compounds were tested for antiviral activity on isolated herpes simplex virus type 1 (HSV-1) DNA polymerase, in a HSV-1 plaque reduction assay, and on a cutaneous HSV-1 infection in guinea pigs. None of the esters inhibited the activity of isolated HSV-1 polymerases. Monoesters with a free carboxylic group and diesters with an aromatic carboxylic ester function were active against the cutaneous herpesa infection. Mono- and diesters with an aromatic phosphonic ester group also showed activity in the plaque-reduction assay. However, mono- and diesters with aliphatic carboxylic ester groups were inactive in all test systems. The results show that all three acidic groups of phosphonoformic acid must be free in order to get antiviral activity at the enzyme level. However, certain esters of this acid may be biotransformed to the acid itself to give antiherpes activity.
