The Safety, Toleration, and Pharmacokinetics Comparison of Two Intravenous Voriconazole Formulations in Healthy Chinese Volunteers after Three Ascending Doses

Abstract

Voriconazole is a triazole antifungal agent with potent activity against a broad spectrum of clinically significant pathogens to treat infections and invasive aspergillosis and immunocompromised patients as prophylactic drug. The large variability of plasma exposure of voriconazole for injection is related with adverse drug reactions (ADRs), including visual impairment, rash and abnormal liver function test. Because the poorly dissolution of voriconazole in aqueous media, the toxicity of the excipient accumulation of sulfobutyl ether-beta-cyclodextrin sodium salt (SBECD) contained in the intravenous voriconazole may occur in renally impaired patients. The Betadex sulfobutyl ether sodium and SBECD as a solubilizer in the new formulation of intravenous voriconazole injection may improve the related ADRs. The present article evaluate the safety, toleration, and pharmacokinetics (PKs) comparison of two intravenous voriconazole injection formulations after three ascending dose administrations in healthy Chinese subjects by a randomized, double-blind, placebo- and positive-controlled trial.