Antifungal efficacy and pharmacodynamics of posaconazole in experimental models of invasive fungal infections

Abstract

Posaconazole is a novel lipophilic antifungal triazole with potent and broad-spectrum activity against opportunistic, endemic and dermatophytic fungi. This activity extends to organisms that are often refractory to existing triazoles, amphotericin B or echinocandins such as Candida glabrata, Candida krusei, Aspergillus terreus, Fusarium spp. and the Zygomycetes. A large number of experimental animal models of invasive fungal infections has demonstrated the potent and broad-spectrum efficacy of posaconazole in vivo, both in normal and in immunocompromised animals. Consistent with these preclinical data, posaconazole showed strong a antifungal efficacy in phase II and phase III clinical trials in immunocompromised patients with oropharyngeal and oesophageal candidiasis and as salvage therapy in patients with invasive fungal infections, and was effective as antifungal prophylaxis in high-risk patients. This paper reviews the preclinical disposition, antifungal efficacy and pharmacodynamics of posaconazole in and its implications for treatment and prevention of invasive fungal infections.