Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1      Pharmacodynamic Properties
Pharmacotherapeutic group: Antivirals for systemic use; direct acting antivirals; phosphonic acid derivatives, ATC code: J05AD01


Foscarnet is an antiviral agent with a broad spectrum inhibiting all known human viruses of the herpes group: herpes simplex virus type 1 and 2; human herpes virus 6; varicella zoster virus; Epstein-Barr virus and cytomegalovirus (CMV) and some retroviruses, including human immunodeficiency virus (HIV) at concentrations not affecting normal cell growth. Foscarnet also inhibits the viral DNA polymerase from hepatitis B virus.


Foscarnet exerts its antiviral activity by a direct inhibition of viral specific DNA polymerase a reverse transcriptase at concentrations that do not affect cellular DNA polymerases. Foscarnet does not require activation (phosphorylation) by thymidine kinase or other kinases and therefore is active in vitro against HSV mutants deficient in thymidine kinase. CMV strains resistant to ganciclovir may be sensitive to foscarnet.
Sensitivity test results expressed as concentration of the drug required to inhibit growth of virus by 50% in cell culture (IC50) vary greatly depending on the assay method used and cell type employed. A number of sensitive viruses and their IC50 are listed below.
Table 3 Foscarnet inhibition of virus multiplication cell culture 

Virus                              IC50 (μm)
CMV                                50 - 800*
HSV-1, HSV-2                       10-130
VZV                                48- 90
EBV                                < 500**
HHV-6                              49
Ganciclovir resistant CMV          190
HSV - TK Minus Mutant              67
HSV - DNA Polymerase Mutant        5-443
HIV-1                              11-32
Zidovudine resistant HTV-1         10-32
* Mean = 269 micrograms
** 97% of viral antigen synthesis inhibited at 500 micrograms 

If no clinical response to foscarnet is observed, viral isolates should be tested for sensitivity to foscarnet since naturally resistant mutants may exist or emerge under selective pressure both in vitro and in vivo.


The mean foscarnet 50% inhibition value for more than one hundred clinical CMV isolates was approximately 270 micrograms /L, while a reversible inhibition of normal cell growth was observed at about 1000 micrograms /L.


There is no evidence of an increased myelotoxicity when foscarnet is used in combination with zidovudine (AZT).

Pharmacokinetic Properties