title: In vitro and in vivo intraleukocytic accumulation of azithromycin (CP-62, 993) and its influence on ex vivo leukocyte chemiluminescence.
abstract: The accumulation of azithromycin in phagocytic cells was studied both in vitro by using a radiolabelled drug and a bioassay and in vivo for 12 volunteers receiving 1.5 g (total dose) orally within 3 days. In vitro, neutrophils and unfractionated blood leukocytes accumulated azithromycin up to 160-fold the extracellular concentration within 1 h at 37 degrees C but less than 3-fold at 4 degrees C. Dead cells accumulated up to 30-fold azithromycin, whereas NaF-treated cells accumulated up to 60-fold arithromycin. The mean efflux from preloaded cells was at most 31.0% +/- 10.6% (standard error of the mean) of the cell-associated concentration within 4 h of incubation at 37 degrees C in drug-free buffer. In vivo, the azithromycin concentration was 45.2 +/- 6.1 mg/liter of intracellular fluid at 2 h after the third dose and 36.6 +/- 8.3 mg/liter at 1 week thereafter. The corresponding concentrations in serum were 0.2 +/- 0.1 (2 h) and less than 0.05 (1 week). The luminol-enhanced chemiluminescence response induced by phorbol myristate acetate, opsonized zymosan, and two opsonized strains of Haemophilus influenzae (a type b capsulated strain and a noncapsulated strain) was also studied ex vivo by using the blood leukocytes from the 12 test volunteers and 4 control volunteers at 2 and 6 h after the third oral dose of azithromycin and at 2, 4, and 7 days thereafter. Azithromycin did not influence this response despite high levels of cellular accumulation.
authors.affiliation: Service de Médecine, Institut Jules Bordet, Université Libre de Bruxelles, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Bonnet
authors.forename: P
authors.initials: P
authors.lastname: Van der Auwera
mesh_terms: D000328:Adult; D017963:Azithromycin; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006193:Haemophilus influenzae / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008163:Luminescent Measurements; D008165:Luminol / Q000494:pharmacology; D008297:Male; D010084:Oxidation-Reduction; D010587:Phagocytosis / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D008165:Luminol; D004917:Erythromycin; D017963:Azithromycin; D013755:Tetradecanoylphorbol Acetate