Intracellular Concentrations of Posaconazole in Different Compartments of Peripheral Blood

被引：44

作者：

Farowski, Fedja ^{[1
]}

Cornely, Oliver A. ^{[1
,2
]}

Vehreschild, Joerg J. ^{[3
]}

Hartmann, Pia

Bauer, Tim ^{[4
]}

Steinbach, Angela ^{[1
]}

Rueping, Maria J. G. T. ^{[1
]}

Mueller, Carsten ^{[4
]}

机构：

[1] Klinikum Univ Koln, Klin Studienzentrum Infektiol 2, Innere Med Klin 1, D-50924 Cologne, Germany

[2] Univ Cologne, ZKS Koln, BMBF 01KN0706, D-50924 Cologne, Germany

[3] Klinikum Univ Koln, Innere Med Klin 1, BMBF 01KI0771, D-50924 Cologne, Germany

[4] Klinikum Univ Koln, Inst Pharmakol, D-50924 Cologne, Germany

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2010年 / 54卷 / 07期

关键词：

INTRAPULMONARY PHARMACOKINETICS; PHARMACODYNAMICS; ITRACONAZOLE; VORICONAZOLE;

D O I：

10.1128/AAC.01407-09

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：2928 / 2931

页数：4

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