Dirithromycin concentrations in bronchial mucosa and secretions.
Since a high tissue penetration of dirithromycin (D) has been assessed in early studies, the aims of this study were to determine D concentrations in bronchial mucosa and secretions in patients suffering from an acute exacerbation of chronic bronchitis (AECB), to compare intra-individual bronchial mucosa and secretion concentrations and to relate bronchial concentrations of D and clinical efficacy. The main inclusion criteria were comprised of (1) AECB, defined by the presence of an increase in dyspnea, sputum production and change in sputum purulence, and (2) clinical indication of fiberoptic bronchoscopy allowing performance of bronchial biopsies. All patients were treated with a 500-mg once-daily D dose for 5 days. Patients were randomly divided into three groups, according to sampling times (24, 48 and 72 h after the last dose). Tissue concentration analyses were performed by one blinded microbiologist (microbiological agar diffusion assay). The results showed: (1) 37 out of the 46 patients (80.4%) had a favorable response to treatment at the time of fiberoptic bronchoscopy (14 cured, 23 improved); (2) bronchial mucosa concentrations were high in all groups, and (3) mean values at 24, 48 and 72 h after the last dose were respectively 6.51 +/- 1.44, 6. 61 +/- 2.7, 5.67 +/- 1.02 mg.kg-1; no statistical difference was observed between the groups. In bronchial secretions collected simultaneously, concentrations were lower, i.e. 1.26 +/- 0.3, 0.61 +/- 0.12, 0.84 +/- 0.12. Significant associations were observed between bronchial mucosa and secretion concentrations (r = 0.71, p = 0.0001), and between clinical response and bronchial concentrations (p = 0.03, Kruskall-Wallis test). In conclusion, these results may confirm the clinical significance of tissue concentrations measured in bronchial tissues of patients with AECB.
Department of Chest Diseases and Internal Medicine, Hôpital de la Cavale Blanche, Brest, France. christophe-leroyer@univ-brest.fer
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Leroyer
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Muller-Serieys
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Quiot
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Benhamou
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Clavier
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Bergogne-Bérézin
D000900:Anti-Bacterial Agents / Q000032:analysis / Q000493:pharmacokinetics; D001980:Bronchi / Q000737:chemistry* / Q000378:metabolism*; D001991:Bronchitis / Q000188:drug therapy / Q000378:metabolism*; D002908:Chronic Disease; D004917:Erythromycin / Q000031:analogs & derivatives / Q000032:analysis / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D018942:Macrolides; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000737:chemistry; D009093:Mucus / Q000737:chemistry; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D018942:Macrolides; C053853:dirithromycin; D004917:Erythromycin