| Indication |
For the treatment of CMV retinitis in patients with acquired
immunodeficiency syndrome (AIDS) and for treatment of
acyclovir-resistant mucocutaneous HSV infections in immunocompromised
patients. |
| Pharmacodynamics |
Foscarnet 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 action |
Foscarnet 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. |
| Absorption |
Poorly absorbed after oral administration (bioavailability from 12 to 22%). |
| Volume of distribution |
Not Available |
| Protein binding |
14-17% |
| Metabolism |
Not metabolized. |
| Route of elimination |
Not Available |
| Half life |
3.3-6.8 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]
|
| Toxicity |
Oral, rat LD50: >2,000 mg/kg. Signs of overdose include renal impairment. |
