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Intracellular concentrations of micafungin in different cellular compartments of the peripheral blood

Fedja Farowski1, Oliver A Cornely, Jörg J Vehreschild

  • 1Universitätsklinikum Köln, Klinik I für Innere Medizin, Köln, Germany. Fedja.Farowski@ctuc.de

International Journal of Antimicrobial Agents
|January 11, 2012
PubMed

Insights

Micafungin concentrates significantly within peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes (PMNs), but not red blood cells (RBCs), in patients. This antifungal drug achieves high intracellular levels in key immune cells.

Area of Science:

  • Pharmacokinetics
  • Cellular Biology
  • Infectious Diseases

Background:

  • Micafungin is an echinocandin antifungal agent.
  • Serum concentrations of micafungin are well-documented.
  • Limited data exist on micafungin's intracellular distribution in peripheral blood cells.

Purpose of the Study:

  • To quantify intracellular micafungin concentrations in peripheral blood cells.
  • To compare intracellular concentrations with plasma levels.
  • To investigate factors influencing micafungin uptake in peripheral blood mononuclear cells (PBMCs).

Main Methods:

  • Blood samples were collected from 26 patients receiving micafungin.
  • Peripheral blood mononuclear cells (PBMCs), polymorphonuclear leukocytes (PMNs), and red blood cells (RBCs) were isolated using Ficoll-Hypaque density gradient centrifugation.
  • Intracellular micafungin concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Main Results:

  • Intracellular micafungin concentrations were significantly higher in PBMCs and PMNs compared to plasma (P<0.001).
  • Intracellular micafungin concentrations in RBCs did not differ significantly from plasma concentrations.
  • In vitro studies indicated that albumin concentration affects PBMC uptake, but only at non-physiological levels.

Conclusions:

  • Micafungin achieves substantial intracellular concentrations in human PBMCs and PMNs.
  • Micafungin is present within RBCs, though not at elevated levels compared to plasma.
  • The uptake of micafungin into PBMCs is influenced by albumin, particularly under non-physiological conditions, suggesting potential implications for drug distribution.

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