title: Intracellular concentrations of posaconazole in different compartments of peripheral blood.
abstract: Therapeutic drug monitoring (TDM) of antifungal plasma concentrations is increasingly recommended. However, data on antifungal concentrations in the other compartments of the peripheral blood are limited. Hence, we collected 23 blood samples from 14 patients receiving posaconazole for prophylaxis of fungal infections. These samples were separated by double-discontinuous Ficoll-Hypaque density gradient centrifugation. The intracellular posaconazole concentrations of the obtained cells, i.e., the peripheral blood mononuclear cells (PBMCs), polymorphonuclear leukocytes (PMNs), and red blood cells (RBCs), were determined by liquid chromatography-tandem mass spectrometry. The intracellular concentrations of the PBMCs and PMNs were significantly higher than those of surrounding media (P < 0.001). The ratios between the intracellular and extracellular concentrations (C/E) were 22.5 +/- 21.2, 7.66 +/- 6.50, and 0.09 +/- 0.05 for the PBMCs, PMNs, and RBCs, respectively. Posaconazole reaches high concentrations within human PBMCs and PMNs and is, to a lesser extent, present in RBCs. The high intracellular concentrations might contribute to posaconazole efficacy and distribution.
authors.affiliation: Klinikum der Universität zu Köln, Klinik I für Innere Medizin, Klinisches Studienzentrum 2 für Infektiologie, Fedja Farowski, MSc, 50924 Cologne, Germany. Fedja.Farowski@ctuc.de
authors.forename: Fedja
authors.initials: F
authors.lastname: Farowski
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Cornely
authors.forename: Jörg J
authors.initials: JJ
authors.lastname: Vehreschild
authors.forename: Pia
authors.initials: P
authors.lastname: Hartmann
authors.forename: Tim
authors.initials: T
authors.lastname: Bauer
authors.forename: Angela
authors.initials: A
authors.lastname: Steinbach
authors.forename: Maria J G T
authors.initials: MJ
authors.lastname: Rüping
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000097:blood* / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D014230:Triazoles / Q000097:blood* / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole
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