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Int J Clin Pract. 2004 Jun;58(6):612-24.

Posaconazole: a potent, extended-spectrum triazole anti-fungal for the treatment of serious fungal infections.

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Département d'Hématologie et d'Oncologie, Hôpital de Hautepierre, Strasbourg, France.


Posaconazole is a potent, extended-spectrum, investigational triazole anti-fungal that is highly active in pre-clinical in vitro and in vivo models against a wide array of yeasts and moulds, including Aspergillus, Fusarium and Zygomycetes, which are often refractory to polyenes and older azoles. In humans, orally administered posaconazole is absorbed under fed or fasted conditions; however, absorption is significantly improved when it is coadministered with food or liquid nutritional supplements and when the daily dose is divided (into two or four daily doses). Unlike newer azoles, posaconazole is not extensively metabolised by cytochrome P450 (CYP) enzymes and is primarily excreted as parent compound in the faeces. Posaconazole is a CYP3A4 inhibitor, but it does not inhibit the activity of other CYP enzymes. Therefore, in comparison with other azole anti-fungal drugs, posaconazole may have the potential for fewer drug interactions. The pharmacokinetics of posaconazole are not influenced by age, gender or race. Dose adjustments for renal or hepatic impairment do not appear to be indicated based on results from single-dose studies. Preliminary efficacy data from clinical trials are promising. As salvage therapy, posaconazole elicited complete or partial responses in 44 to 75% of patients (N = 97) with invasive fungal infections who were intolerant of, or who had disease refractory to, amphotericin B or itraconazole. In an analysis of patients with aspergillosis, a 42% success rate was observed in the posaconazole arm (n = 107) compared with a 26% success rate in the control arm (n = 86). Importantly, Kaplan-Meier analysis demonstrated a survival benefit in posaconazole-treated patients. Moreover, posaconazole yielded complete or partial responses in 71% of patients with zygomycosis (N = 24). Posaconazole appears to be well tolerated over long-term administration (>1 year) and may represent an important addition to the anti-fungal armamentarium.

[Indexed for MEDLINE]

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