{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:25:45Z","timestamp":1786976745143,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,4,23]],"date-time":"2015-04-23T00:00:00Z","timestamp":1429747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Itraconazole and clarithromycin are clinically effective in the treatment of chronic rhinosinusitis (CRS) through incompletely understood anti\u2010inflammatory properties. P\u2010glycoprotein (P\u2010gp) is overexpressed in CRS and inhibition results in decreased inflammatory cytokine secretion. Both itraconazole and clarithromycin have also been shown to have P\u2010gp inhibitory properties in other tissues, suggesting a novel explanation for their immunomodulatory effects in CRS. The purpose of this study is to therefore confirm whether these drugs are capable of inhibiting P\u2010gp specifically in sinonasal epithelial cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This was an institutional review board (IRB)\u2010approved study in which primary sinonasal epithelial cells were cultured in 96\u2010well plates. A Calcein AM assay was used to quantify P\u2010gp inhibition as determined by an increase in intracellular fluorescence. A dose\u2010response curve was generated for itraconazole and clarithromycin (maximal concentration 100\u00a0\u03bcM) and compared to that of Zosuquidar, a highly specific known P\u2010gp inhibitor. Results were compared using a Student\n                      <jats:italic>t<\/jats:italic>\n                      test with a significance defined as\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both itraconazole and clarithromycin demonstrated a dose\u2010response curve for P\u2010gp inhibition similar to that of Zosuquidar. The respective maximal inhibitory concentrations of Zosuquidar, itraconazole, and clarithromycin prior to induction of cytotoxicity were 0.31, 3.13, and 1.56\u00a0\u03bcM, respectively, as demonstrated by a statistically significant increase in total intracellular fluorescence (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05 in all groups).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Both itraconazole and clarithromycin are capable of inhibiting sinonasal epithelial cell associated P\u2010gp. The anti\u2010inflammatory effects of these agents in CRS may be attributable, in part, to their heretofore unrecognized P\u2010gp modulatory properties.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alr.21454","type":"journal-article","created":{"date-parts":[[2015,4,24]],"date-time":"2015-04-24T01:01:02Z","timestamp":1429837262000},"page":"477-480","source":"Crossref","is-referenced-by-count":17,"title":["Itraconazole and clarithromycin inhibit P\u2010glycoprotein activity in primary human sinonasal epithelial cells"],"prefix":"10.1002","volume":"5","author":[{"given":"Allen","family":"Lam","sequence":"first","affiliation":[{"name":"Massachusetts Eye and Ear Infirmary Harvard Medical School  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Hoang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Boston University  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Singleton","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Boston University  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Boston University  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin S.","family":"Bleier","sequence":"additional","affiliation":[{"name":"Massachusetts Eye and Ear Infirmary Harvard Medical School  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,4,23]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOO.0b013e32835bc3f9"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2010.02381.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2005.11.016"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21004"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21176"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21316"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2009.07.006"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2009.23.3315"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.2500\/aap.2013.34.3636"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOO.0000000000000022"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/000164801300006326"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0022215112000485"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-009-0033-2"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajr.2008.22.3115"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000345861"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21166"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.10109FP"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.22566"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2011.587033"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.34.469"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-199712000-00016"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200001000-00023"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-013-0416-2"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1385\/CRIAI:30:3:187"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.03.038"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.09.037"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.20064"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/194589240301700101"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-2586"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12354"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1586\/ers.12.35"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-277269"},{"key":"e_1_2_5_34_1","volume-title":"Clarithromycin","year":"2013"},{"key":"e_1_2_5_35_1","volume-title":"Itraconazole","year":"2013"}],"container-title":["International Forum of Allergy &amp; 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