Foscarnet

Foscarnet is a phosphonoformate derivative that does not require phosphorylation for antiviral activity. Although it is not an antimetabolite, foscarnet inhibits viral RNA polymerase, DNA polymerase, and HIV reverse transcriptase. Resistance involves point mutations in the DNA polymerase gene. Foscarnet is given intravenously and penetrates well into tissues, including the CNS. The drug undergoes renal elimination in direct proportion to creatinine clearance. It is used for acyclovir-resistant HSV and herpes zoster infections. Foscarnet works by reversibly inhibiting viral DNA and RNA polymerases, thereby interfering with viral DNA and RNA synthesis. Mutation of the polymerase structure is responsible for resistant viruses. [Note: Cross-resistance between foscarnet and ganciclovir or acyclovir is uncommon.] Foscarnet is poorly absorbed orally and must be injected IV. It must also be given frequently to avoid relapse when plasma levels fall. It is dispersed throughout the body and greater than 10 percent enters the bone matrix, from which it slowly leaves. The parent drug is eliminated by glomerular filtration andtubular secretion into the urine