Effect of Macrolides on In Vivo Ion Transport across Cystic Fibrosis Nasal Epithelium

• Published in: American journal of respiratory and critical care medicine Vol. 171; no. 8; pp. 868 - 871
• Main Authors: Barker, Pierre M, Gillie, Daniel J, Schechter, Michael S, Rubin, Bruce K
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 15.04.2005; American Lung Association; American Thoracic Society
• Subjects: Adolescent; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Azithromycin - pharmacokinetics; Azithromycin - pharmacology; Azithromycin - therapeutic use; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Child; Clarithromycin - pharmacokinetics; Clarithromycin - pharmacology; Clarithromycin - therapeutic use; Cross-Over Studies; Cystic Fibrosis - drug therapy; Cystic Fibrosis - physiopathology; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Double-Blind Method; Emergency and intensive care: techniques, logistics; Humans; Intensive care medicine; Intensive care unit. Emergency transport systems. Emergency, hospital ward; Ion Transport - drug effects; Macrolides - pharmacokinetics; Macrolides - pharmacology; Macrolides - therapeutic use; Male; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred CFTR; Mice, Knockout; Nasal Mucosa - drug effects; Nasal Mucosa - physiopathology; Pharmacology. Drug treatments; Intensive care; Respiratory disease; therapy; Ion transport; Metabolic diseases; Cystic fibrosis; Epithelium; Macrolide; Genetic disease; Antibiotic; Treatment; nasal potential difference; Chlorides; Digestive diseases; chloride; Resuscitation; Pancreatic disease
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200311-1508OC

Fourteen- and 15-member macrolide antibiotics are under investigation as potential therapeutic agents for cystic fibrosis (CF). The nonantibiotic mechanisms of action of these compounds in CF are not understood. We used nasal potential difference (NPD) measurements to test the effect of macrolides on airway epithelial ion (chloride, sodium) transport of CF mice and humans. We tested clarithromycin and azithromycin in mice, and clarithromycin in patients with CF. Baseline and post-treatment NPD was measured in two strains (C57Bl6 and BalbC) of CF transmembrane regulator "knockout" and littermate control mice, and in DeltaF508/DeltaF508 mice. In addition, NPD was measured in 18 human subjects with CF (17 DeltaF-508/DeltaF-508 and 1 DeltaF-508/other) who were undergoing a 12-month, randomized, double-blind crossover study of the effects of clarithromycin on pulmonary outcome in CF. Neither clarithromycin nor azithromycin affected ion transport characteristics of normal or CF nasal epithelium in either mouse or humans. We conclude that the apparent beneficial effects of macrolides on pulmonary outcome in CF are not mediated by their modulation of ion transport.