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Effect of single oral dose of azithromycin, clarithromycin, and roxithromycin on polymorphonuclear leukocyte function assessed ex vivo by flow cytometry.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 1996 Sep; Vol. 40 (9), pp. 2039-42. - Publication Year :
- 1996
-
Abstract
- Azithromycin was given as a single oral dose (20 mg/kg of body weight) to 12 volunteers in a crossover study with roxithromycin (8 to 12 mg/kg) and clarithromycin (8 to 12 mg/kg). Flow cytometry was used to study the phagocytic functions and the release of reactive oxygen products following phagocytosis by neutrophil granulocytes prior to administration of the three drugs, 16 h after azithromycin administration, and 3 h after clarithromycin and roxithromycin administration. Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocyanate-labeled bacteria. Reactive oxygen generation after phagocytosis of unlabeled bacteria was estimated by the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly. Azithromycin resulted in decreased capacities of the cells to phagocytize Escherichia coli (median [range], 62% [27 to 91%] of the control values; P < 0.01) and generate reactive oxygen products (75% [34 to 26%] of the control values; P < 0.01). Clarithromycin resulted in reduced phagocytosis (82% [75 to 98%] of control values; P < 0.01) but did not alter reactive oxygen production (84% [63 to 113%] of the control values; P > 0.05). Roxithromycin treatment did not affect granulocyte phagocytosis (92% [62 to 118%] of the control values; P > 0.05) or reactive oxygen production (94% [66 to 128%] of the control value; P > 0.05). No relation between intra- and/or extracellular concentrations of azithromycin and/or roxithromycin and the polymorphonuclear phagocyte function and/or reactive oxygen production existed (P > 0.05 for all comparisons). These results demonstrate that the accumulation of macrolides in neutrophils can suppress the response of phagocytic cells to bacterial pathogens after a therapeutic dose.
- Subjects :
- Adult
Anti-Bacterial Agents metabolism
Azithromycin metabolism
Chromatography, High Pressure Liquid
Clarithromycin metabolism
Cross-Over Studies
Escherichia coli drug effects
Female
Flow Cytometry
Humans
Male
Neutrophils metabolism
Phagocytosis drug effects
Reactive Oxygen Species metabolism
Roxithromycin metabolism
Anti-Bacterial Agents pharmacology
Azithromycin pharmacology
Clarithromycin pharmacology
Neutrophils drug effects
Roxithromycin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0066-4804
- Volume :
- 40
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 8878577
- Full Text :
- https://doi.org/10.1128/AAC.40.9.2039