Effect of Macrolides on In Vivo Ion Transport across Cystic Fibrosis Nasal Epithelium
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 o...
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| Veröffentlicht in: | American journal of respiratory and critical care medicine 2005-04, Vol.171 (8), p.868-871 |
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| creator | Barker, Pierre M Gillie, Daniel J Schechter, Michael S Rubin, Bruce K |
| description | 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. |
| doi_str_mv | 10.1164/rccm.200311-1508OC |
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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.</description><identifier>ISSN: 1073-449X</identifier><identifier>EISSN: 1535-4970</identifier><identifier>DOI: 10.1164/rccm.200311-1508OC</identifier><identifier>PMID: 15657462</identifier><language>eng</language><publisher>New York, NY: Am Thoracic Soc</publisher><subject>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</subject><ispartof>American journal of respiratory and critical care medicine, 2005-04, Vol.171 (8), p.868-871</ispartof><rights>2005 INIST-CNRS</rights><rights>Copyright American Thoracic Society Apr 15, 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-c149de817f8bb878ce376400397ece79ff92138208ff7d97a8f8f558df31c9aa3</citedby><cites>FETCH-LOGICAL-c417t-c149de817f8bb878ce376400397ece79ff92138208ff7d97a8f8f558df31c9aa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,4011,4012,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16713039$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15657462$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Barker, Pierre M</creatorcontrib><creatorcontrib>Gillie, Daniel J</creatorcontrib><creatorcontrib>Schechter, Michael S</creatorcontrib><creatorcontrib>Rubin, Bruce K</creatorcontrib><title>Effect of Macrolides on In Vivo Ion Transport across Cystic Fibrosis Nasal Epithelium</title><title>American journal of respiratory and critical care medicine</title><addtitle>Am J Respir Crit Care Med</addtitle><description>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.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Azithromycin - pharmacokinetics</subject><subject>Azithromycin - pharmacology</subject><subject>Azithromycin - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Child</subject><subject>Clarithromycin - pharmacokinetics</subject><subject>Clarithromycin - pharmacology</subject><subject>Clarithromycin - therapeutic use</subject><subject>Cross-Over Studies</subject><subject>Cystic Fibrosis - drug therapy</subject><subject>Cystic Fibrosis - physiopathology</subject><subject>Cystic Fibrosis Transmembrane Conductance Regulator - genetics</subject><subject>Double-Blind Method</subject><subject>Emergency and intensive care: techniques, logistics</subject><subject>Humans</subject><subject>Intensive care medicine</subject><subject>Intensive care unit. Emergency transport systems. Emergency, hospital ward</subject><subject>Ion Transport - drug effects</subject><subject>Macrolides - pharmacokinetics</subject><subject>Macrolides - pharmacology</subject><subject>Macrolides - therapeutic use</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Potentials - drug effects</subject><subject>Membrane Potentials - physiology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred CFTR</subject><subject>Mice, Knockout</subject><subject>Nasal Mucosa - drug effects</subject><subject>Nasal Mucosa - physiopathology</subject><subject>Pharmacology. Drug treatments</subject><issn>1073-449X</issn><issn>1535-4970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkNFqFDEUhoMotlZfwAsJggUvpuZMMpOTS1m2ulDtTSvehWwmcbNkZtZkRunbN-ssFLzKCXznT_6PkLfArgBa8SlZ21_VjHGAChqGt6tn5Bwa3lRCSfa8zEzySgj184y8ynnPGNQI7CU5g6ZtpGjrc3K_9t7ZiY6efjM2jTF0LtNxoJuB_gh_Rrop810yQz6MaaJHJGe6eshTsPQ6bMs1ZPrdZBPp-hCmnYth7l-TF97E7N6czgtyf72-W32tbm6_bFafbyorQE6VBaE6hyA9brco0TouW1EKKemsk8p7VQPHmqH3slPSoEffNNh5DlYZwy_I5ZJ7SOPv2eVJ9yFbF6MZ3Dhn3UpZAyIU8P1_4H6c01D-pkGplgEKXqB6gf6VTM7rQwq9SQ8amD4a10fjejGuF-Nl6d0ped72rntaOSkuwIcTYLI10ReXNuQnrpXAS-PCfVy4Xfi1-xuS07k3MZZY0GZ_fBkkaNTYIn8E6QyXew</recordid><startdate>20050415</startdate><enddate>20050415</enddate><creator>Barker, Pierre M</creator><creator>Gillie, Daniel J</creator><creator>Schechter, Michael S</creator><creator>Rubin, Bruce K</creator><general>Am Thoracic Soc</general><general>American Lung Association</general><general>American Thoracic Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20050415</creationdate><title>Effect of Macrolides on In Vivo Ion Transport across Cystic Fibrosis Nasal Epithelium</title><author>Barker, Pierre M ; Gillie, Daniel J ; Schechter, Michael S ; Rubin, Bruce K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-c149de817f8bb878ce376400397ece79ff92138208ff7d97a8f8f558df31c9aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Azithromycin - pharmacokinetics</topic><topic>Azithromycin - pharmacology</topic><topic>Azithromycin - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Child</topic><topic>Clarithromycin - pharmacokinetics</topic><topic>Clarithromycin - pharmacology</topic><topic>Clarithromycin - therapeutic use</topic><topic>Cross-Over Studies</topic><topic>Cystic Fibrosis - drug therapy</topic><topic>Cystic Fibrosis - physiopathology</topic><topic>Cystic Fibrosis Transmembrane Conductance Regulator - genetics</topic><topic>Double-Blind Method</topic><topic>Emergency and intensive care: techniques, logistics</topic><topic>Humans</topic><topic>Intensive care medicine</topic><topic>Intensive care unit. Emergency transport systems. Emergency, hospital ward</topic><topic>Ion Transport - drug effects</topic><topic>Macrolides - pharmacokinetics</topic><topic>Macrolides - pharmacology</topic><topic>Macrolides - therapeutic use</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Potentials - drug effects</topic><topic>Membrane Potentials - physiology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred CFTR</topic><topic>Mice, Knockout</topic><topic>Nasal Mucosa - drug effects</topic><topic>Nasal Mucosa - physiopathology</topic><topic>Pharmacology. Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barker, Pierre M</creatorcontrib><creatorcontrib>Gillie, Daniel J</creatorcontrib><creatorcontrib>Schechter, Michael S</creatorcontrib><creatorcontrib>Rubin, Bruce K</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of respiratory and critical care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barker, Pierre M</au><au>Gillie, Daniel J</au><au>Schechter, Michael S</au><au>Rubin, Bruce K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Macrolides on In Vivo Ion Transport across Cystic Fibrosis Nasal Epithelium</atitle><jtitle>American journal of respiratory and critical care medicine</jtitle><addtitle>Am J Respir Crit Care Med</addtitle><date>2005-04-15</date><risdate>2005</risdate><volume>171</volume><issue>8</issue><spage>868</spage><epage>871</epage><pages>868-871</pages><issn>1073-449X</issn><eissn>1535-4970</eissn><abstract>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.</abstract><cop>New York, NY</cop><pub>Am Thoracic Soc</pub><pmid>15657462</pmid><doi>10.1164/rccm.200311-1508OC</doi><tpages>4</tpages></addata></record> |
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| source | MEDLINE; American Thoracic Society (ATS) Journals Online; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Journals@Ovid Complete |
| 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 |
| title | Effect of Macrolides on In Vivo Ion Transport across Cystic Fibrosis Nasal Epithelium |
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