This is one of the first studies to report on therapeutic drug monitoring (TDM) of posaconazole (PCZ) for antifungal prophylaxis in patients with acute myelogenous leukaemia or myelodysplastic syndrome outside of the rigours of clinical licencing trials. A number of factors have been identified or proposed as causing poor oral absorption of PCZ. Putative PCZ concentrations have been recommended for TDM (0.5 μg/mL or 0.7 μg/mL). In this study, 19 (90.5%) of 21 patients failed to reach the higher putative target of 0.7 μg/mL, and 16 patients (76.2%) failed to reach the lower target of 0.5 μg/mL. Increasing the dose did not help four of six patients reach target concentrations. Three of the patients developed 'proven' or 'possible' fungal infections, all with PCZ concentrations <0.5 μg/mL. Use of acid-suppressing agents appears to explain some of the poor absorption. TDM of PCZ is warranted in patients receiving this orally administered agent.

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http://dx.doi.org/10.1016/j.ijantimicag.2010.11.021DOI Listing

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