title: Cellular uptake and efflux of azithromycin, erythromycin, clarithromycin, telithromycin, and cethromycin.
abstract: 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.
authors.affiliation: PLIVA Research Institute Ltd., Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia. martina.bosnar@pliva.hr
authors.forename: Martina
authors.initials: M
authors.lastname: Bosnar
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Kelnerić
authors.forename: Vesna
authors.initials: V
authors.lastname: Munić
authors.forename: Vesna
authors.initials: V
authors.lastname: Eraković
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parnham
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000493:pharmacokinetics; D017963:Azithromycin / Q000378:metabolism / Q000493:pharmacokinetics; D002460:Cell Line; D017291:Clarithromycin / Q000378:metabolism / Q000493:pharmacokinetics; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism*; D004917:Erythromycin / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D048628:Ketolides / Q000378:metabolism / Q000493:pharmacokinetics; D018942:Macrolides / Q000378:metabolism* / Q000493:pharmacokinetics; D051379:Mice; D009504:Neutrophils / Q000378:metabolism*; D010586:Phagocytes / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D004917:Erythromycin; D017963:Azithromycin; D017291:Clarithromycin; C405499:cethromycin; C106791:telithromycin