CLINICAL-PHARMACOLOGY - FOSCARNET

Foscarnet exerts its antiviral effects via reversible inhibition of viral polymerases. Pharmacodynamic data indicate that herpesvirus and human immunodeficiency virus replication is inhibited by therapeutically achievable concentrations of foscarnet; however, the concentrations of foscarnet required for such inhibition have been found to vary widely. Pharmacokinetic data indicate that foscarnet is eliminated via the renal route, undergoes negligible metabolism, and appears to be distributed widely from the circulation. However, the available data indicate that the pharmacokinetics of the drug varies among patients and within the individual patient, particularly with regard to plasma drug levels; furthermore, such factors as the intracellular kinetics of the drug have yet to be well characterized. It is thus difficult to formulate optimal dosing regimens on the basis of what is known of foscarnet pharmacodynamics and pharmacokinetics. Nevertheless, dosages that produce clear-cut therapeutic benefits without unacceptable toxicity have been identified in clinical trials of foscarnet in acquired immunodeficiency syndrome (AIDS) patients with cytomegalovirus (CMV) retinitis.