IS THERE A PHARMACOKINETIC INTERACTION BETWEEN FOSCARNET AND ZALCITABINE DURING CONCOMITANT ADMINISTRATION

Foscarnet, an antiviral agent used in the treatment of cytomegalovirus infection, and zalcitabine, an antiretroviral nucleoside analogue use d in the treatment of human immunodeficiency virus infection, are comm only used concomitantly. Foscarnet and zalcitabine may interact pharma cokinetically, as both compounds are partially eliminated by renal tub ular secretion. Owing to dose-related toxicities associated with these two drugs, it is essential that we have data regarding their pharmaco kinetic disposition during concomitant therapy. Twelve patients random ly received either foscarnet (four doses) or zalcitabine (five doses) (Phase 1), followed by concomitant foscarnet (four doses) and zalcitab ine (six doses) (Phase 2), followed by dosing with the drug not receiv ed in Phase 1 (Phase 3). Following the last dose in each phase of the study, serial plasma samples were collected over 8 hours for zalcitabi ne and over 12 hours for fuscarnet to determine the pharmacokinetics o f each drug using noncompartmental analysis. Foscarnet plasma and urin e levels were determined using high-performance liquid chromatography, and zalcitabine levels were determined using radioimmunoassay. No cli nically significant alterations in the pharmacokinetics of foscarnet o r zalcitabine occurred in this study. Thus despite the potential for f oscarnet and zalcitabine to compete for renal tubular secretion, no ap parent pharmacokinetic interaction exists between these two drugs at t he clinically relevant doses studied.