title: Penetration of macrolides into human polymorphonuclear leucocytes.
abstract: Five 14C-labelled macrolide antibiotics (erythromycin, josamycin, clarithromycin (TE-031), rokitamycin and roxithromycin) were studied for their transport into human polymorphonuclear leucocytes. Intracellular/extracellular concentration ratios (transport ratios) of these macrolides were quite high: erythromycin, 6.6; josamycin, 15.5; clarithromycin, 16.4; rokitamycin, 30.5; and roxithromycin, 21.9. When polymorphonuclear leucocytes were pre-treated with formaldehyde or incubated at 4 degrees C, or at low pH, transport ratios were reduced. When extracellular macrolide was removed, intracellular macrolide concentrations became as low as 30% of the pre-wash concentrations in 5 min. KF lowered the transport ratios of josamycin and rokitamycin in particular and NaCN reduced the transport ratios of erythromycin and josamycin strikingly. Ouabain slightly lowered transport ratios of all the antibiotics tested except roxithromycin, and 2, 4-dinitrophenol decreased the transport ratio of clarithromycin markedly. The addition of various amino acids or hexose did not inhibit the transfer. Adenosine, however, inhibited the transfer of these antibiotics except erythromycin and lowered transport ratios by 83 to 92%. Puromycin reduced transport ratios of the same antibiotics by 59 to 95%. With polymorphonuclear leucocytes that had phagocytosed Legionella pneumophila serogroup 1, transport ratios of all five drugs tended to decrease. However, when Staphylococcus aureus ATCC 25923 or opsonized zymosan was phagocytosed, transport ratios for macrolides, except for roxithromycin, increased.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ishiguro
authors.forename: H
authors.initials: H
authors.lastname: Koga
authors.forename: S
authors.initials: S
authors.lastname: Kohno
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: M
authors.initials: M
authors.lastname: Hirota
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D000963:Antimetabolites / Q000494:pharmacology; D001693:Biological Transport, Active; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007875:Legionella / Q000187:drug effects / Q000378:metabolism; D018942:Macrolides; D009504:Neutrophils / Q000378:metabolism*; D009705:Nucleosides / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000963:Antimetabolites; D018942:Macrolides; D009705:Nucleosides; D015054:Zymosan