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Antimicrobial Agents and Chemotherapy, June 2005, p. 2372-2377, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2372-2377.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Cellular Uptake and Efflux of Azithromycin, Erythromycin, Clarithromycin, Telithromycin, and Cethromycin

Martina Bosnar,^* eljko Kelneri, Vesna Muni, Vesna Erakovi, and Michael J. Parnham

PLIVA Research Institute Ltd., Prilaz baruna Filipovia 29, HR-10000 Zagreb, Croatia

Received 9 November 2004/ Returned for modification 21 December 2004/ Accepted 22 February 2005

Macrolide antibiotics have an outstanding ability to concentrate within host cells, particularly phagocytes. In the study described in this paper five different macrolide antibiotics were compared regarding the uptake and release kinetics in human peripheral blood polymorphonuclear neutrophils (PMNs) and three different cell lines, two phagocytic cell lines (RAW 264.7 and THP-1) and an epithelial cell line (MDCK). Based on the results obtained, the substances tested could be clustered into different groups. Azithromycin constituted the first group, characterized by rapid and nonsaturable uptake into phagocytic cells and a high degree of retention in the preloaded cells. The second group included erythromycin and clarithromycin. These two substances do not exhibit cell specificity; consequently, they are taken up to a similar extent and are released by all cell types studied. Ketolides constituted the last group. Their uptake was saturable in cells of monocytic lineage as well as in nondifferentiated cells of myeloid lineage, and they were rapidly released from all the cell lines studied. However, in PMNs, ketolide uptake was not saturable; and unlike telithromycin, cethromycin rapidly egressed from the loaded cells.