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 used in the treatment of human immunodeficiency virus infection, are commonly used concomitantly. Foscarnet and zalcitabine may interact pharmacokinetically, as both compounds are partially eliminated by renal tubular secretion. Owing to dose-related toxicities associated with these two drugs, it is essential that we have data regarding their pharmacokinetic disposition during concomitant therapy. Twelve patients randomly received either foscarnet (four doses) or zalcitabine (five doses) (Phase 1), followed by concomitant foscarnet (four doses) and zalcitabine (six doses) (Phase 2), followed by dosing with the drug not received in Phase 1 (Phase 3). Following the last dose in each phase of the study, serial plasma samples were collected over 8 hours for zalcitabine and over 12 hours for foscarnet to determine the pharmacokinetics of each drug using noncompartmental analysis. Foscarnet plasma and urine levels were determined using high-performance liquid chromatography, and zalcitabine levels were determined using radioimmunoassay. No clinically significant alterations in the pharmacokinetics of foscarnet or zalcitabine occurred in this study. Thus despite the potential for foscarnet and zalcitabine to compete for renal tubular secretion, no apparent pharmacokinetic interaction exists between these two drugs at the clinically relevant doses studied.
Aweeka
F T
FT
Department of Clinical Pharmacy, University of California, San Francisco, USA.
Brody
S R
SR
Jacobson
M
M
Botwin
K
K
Martin-Munley
S
S
D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D005260:Female; D017245:Foscarnet / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006679:HIV Seropositivity / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D016047:Zalcitabine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D017245:Foscarnet; D016047:Zalcitabine