gms | German Medical Science

10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010)

Deutsche Gesellschaft für Infektiologie,
Deutsche AIDS-Gesellschaft,
Deutsche Gesellschaft für Tropenmedizin und Internationale Gesundheit,
Paul-Ehrlich-Gesellschaft für Chemotherapie

23.06. - 26.06.2010, Köln

Intracellular concentrations of azoles and echinocandins in different compartments of the peripheral blood

Intrazelluläre Konzentrationen von Azolen und Echinocandinen in verschiedenen Kompartimenten des peripheren Blutes

Meeting Abstract

  • F. Farowski - Uniklinik Köln, Klinik I für Innere Medizin, Köln, Germany
  • C. Müller - Uniklinik Köln, Institut für Pharmakologie, Köln, Germany
  • M.J. Rüping - Uniklinik Köln, Klinik I für Innere Medizin, Köln, Germany
  • J.J. Vehreschild - Uniklinik Köln, Klinik I für Innere Medizin (BMBF 01KI0771), Köln, Germany
  • O.A. Cornely - Uniklinik Köln, Klinik I für Innere Medizin, Köln, Germany; Zentrum für Klinische Studien (ZKS Köln, BMBF 01KN0706), Köln, Germany

10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010). Köln, 23.-26.06.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocMYK 04-4

DOI: 10.3205/10kit047, URN: urn:nbn:de:0183-10kit0475

Veröffentlicht: 2. Juni 2010

© 2010 Farowski et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: While serum and plasma concentrations of antifungal drugs are usually measured during routine therapeutic drug monitoring, little is known about the concentrations in other compartments of the peripheral blood, i.e. peripheral blood mononuclear cells (PBMCs), polymorphonuclear leucocytes (PMNs), and red blood cells (RBCs). Interactions with these cells might well influence the efficacy of antifungal drugs. Synergy on intracellular killing of fungi has been described for itraconazole and voriconazole. However, these experiments were conducted in protein-free medium; hence the intracellular concentrations studied were criticized. We developed a method to quantitate most clinically relevant antifungal drugs in different compartments of the peripheral blood. Based on this method we determine the intracellular concentrations of anidulafungin (ANF), caspofungin (CSF), micafungin (MCF), posaconazole (PSC), and voriconazole (VRC).

Methods: We developed a liquid chromatography tandem mass spectroscopy (LC-MS/MS) assay allowing the quantitation of ANF, CSF, isavuconazole (ISC), MCF, PSC, and VRC in different compartments of the peripheral blood. The lower limits of quantitation [ng/mL] were: ANF 64, CSF 108, ISC 4.5, MCF 160, PSC 10, and VRC 4.2. Samples: Whole blood from patients receiving antifungal treatment was collected in two EDTA salt containing tubes (2x8 mL). The blood was separated by double discontinuous Ficoll Hypaque density gradient centrifugation. Antifungals were extracted from cells with acetonitrile containing internal standard by sonication, vortexing and centrifugation.

Results: Up to now, 23 samples of 14 subjects receiving posaconazole for prophylaxis of fungal infections were analyzed. While posaconazole concentrations within the PBMCs and PMNs were significantly increased compared to the plasma concentration (12.8 µg/mL and 4.0 µg/mL versus 0.6 µg/mL, respectively; P<0.001, t-test), the concentration within RBCs was significantly decreased compared to all other compartments (0.05 µg/mL versus 0.6 µg/mL for plasma; P<0.001, t-test). At the time of writing data on the intracellular concentrations of other azoles and echinocandins is pending.

Conclusion: After establishing a method to determine the concentration of azoles and echinocandins in different compartments of the peripheral blood we showed that the intracellular posaconazole concentration within PBMCs and PMNs was significantly increased (22.5-fold and 7.66-fold).