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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: ATP Binding Cassette Transporter, Subfamily B, Member 1, Anti-Bacterial Agents, Antifungal Agents, Cells, Cultured, Clarithromycin, Dibenzocycloheptenes, Dose-Response Relationship, Drug, Epithelial Cells, Fluoresceins, Fluorescent Dyes, Humans, Itraconazole, Paranasal Sinuses, Quinolines, Th2 Cells.
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Do itraconazole and clarithromycin inhibit P-glycoprotein activity in primary human sinonasal epithelial cells? Context: Itraconazole and clarithromycin are clinically effective in the treatment of chronic rhinosinusitis (CRS) through incompletely understood anti-inflammatory properties. P-glycoprotein (P-gp) is overexpressed in CRS and inhibition results in decreased inflammatory cytokine secretion. Both itraconazole and clarithromycin have also been shown to have P-gp 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-gp specifically in sinonasal epithelial cells. This was an institutional review board (IRB)-approved study in which primary sinonasal epithelial cells were cultured in 96-well plates. A Calcein AM assay was used to quantify P-gp inhibition as determined by an increase in intracellular fluorescence. A dose-response curve was generated for itraconazole and clarithromycin (maximal concentration 100 μM) and compared to that of Zosuquidar, a highly specific known P-gp inhibitor. Results were compared using a Student t test with a significance defined as p < 0.05. Both itraconazole and clarithromycin demonstrated a dose-response curve for P-gp 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 μM, respectively, as demonstrated by a statistically significant increase in total intracellular fluorescence (p < 0.05 in all groups).
assistant
Both itraconazole and clarithromycin are capable of inhibiting sinonasal epithelial cell associated P-gp. The anti-inflammatory effects of these agents in CRS may be attributable, in part, to their heretofore unrecognized P-gp modulatory properties. Final Decision: yes