Intracellular concentrations of anidulafungin in different compartments of the peripheral blood

Abstract

Pharmacokinetic studies usually focus on serum concentrations, hence little is known about intracellular drug concentrations. In this study, we determined the concentration of anidulafungin within different cellular compartments of the peripheral blood. Blood samples (n=17) from patients receiving anidulafungin were collected and separated by double-discontinuous Ficoll-Hypaque density gradient centrifugation. Intracellular concentrations within the obtained cells, i.e. peripheral blood mononuclear cells (PBMCs), polymorphonuclear leucocytes (PMNs) and red blood cells (RBCs), were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). Within the PBMCs and PMNs, the intracellular concentration of anidulafungin was significantly increased compared with the plasma concentration (P<0.001). However, the concentration within RBCs did not significantly differ from the plasma concentration. Anidulafungin reaches high concentrations in human PBMCs and PMNs and is present in RBCs. In vitro data showed that intracellular uptake of anidulafungin by PBMCs depends on the albumin concentration of the surrounding medium, but only at low, i.e. non-physiological, protein concentrations.