Blood and tissue distribution of posaconazole in a rat model of invasive pulmonary aspergillosis

Abstract

Posaconazole is the recommended prophylactic agent in patients at high risk of invasive fungal infection, since adequate drug levels seem to be reached in target sites despite the relatively low levels detected in blood. The objective of this study is to obtain pharmacokinetic (PK) information associated to blood and tissue distribution of posaconazole in an animal model of invasive pulmonary aspergillosis. The PK parameters in lung samples were systematically higher than in serum. After multiple-dose administration of posaconazole, a significant accumulation of the drug was evident in lung tissue. The PK behavior of posaconazole in this particular experimental model is similar to that observed in humans. Thus, we believe this model could be a valid tool to evaluate posaconazole exposure-response relationship.

Keywords: Aspergillus fumigatus; Posaconazole exposure; Tissue concentration.