Abstract
Posaconazole is a second-generation triazole agent with a potent and broad antifungal activity. In addition to the oral suspension, a delayed-release tablet and intravenous formulation with improved pharmacokinetic properties have been introduced recently. Due to the large interindividual and intraindividual variation in bioavailability and drug-drug interactions, therapeutic drug monitoring (TDM) is advised to ensure adequate exposure and improve clinical response for posaconazole. Here, we highlight and discuss the most recent findings on pharmacokinetics and pharmacodynamics of posaconazole in the setting of prophylaxis and treatment of fungal infections and refer to the challenges associated with TDM of posaconazole.
Highlights
Invasive fungal disease (IFD) is associated with substantial morbidity and mortality [1]
We present recent findings on pharmacokinetics and pharmacodynamics of posaconazole in the setting of prophylaxis and treatment of fungal infections
A target trough level of 0.9 mg/l can be suggested based on AUC/minimum fungicidal inhibitory concentration (MIC) ratios (Table 2), a trough level of >0.5 mg/l was recently found to be effective in hematology patients treated with posaconazole tablets [37]
Summary
Invasive fungal disease (IFD) is associated with substantial morbidity and mortality [1]. We present recent findings on pharmacokinetics and pharmacodynamics of posaconazole in the setting of prophylaxis and treatment of fungal infections. A limited role may remain for the oral suspension, for example, in the treatment of patients who are unable to take tablets, such as patients with dysphagia, children, or patients with enteral feeding tubes [8], as the tablet must be swallowed whole (not divided, crushed, or chewed) For these patients, TDM should be applied to assure adequate exposure (see below). With the introduction of the new posaconazole formulations, two additional suitable treatment options can be chosen, which have significantly improved the pharmacokinetics and clinical utility of this antifungal agent compared to the oral suspension [24]. The proposed targets could only be reached by a limited number of subjects for less sensitive strains of Aspergillus spp., which are still considered to be susceptible
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