{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T18:29:06Z","timestamp":1765823346907,"version":"3.48.0"},"reference-count":23,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"unspecified","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000241","name":"Physicians\u2019 Services Incorporated Foundation","doi-asserted-by":"crossref","award":["#04-51"],"award-info":[{"award-number":["#04-51"]}],"id":[{"id":"10.13039\/501100000241","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","award":["#MOP 77569"],"award-info":[{"award-number":["#MOP 77569"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2023,1,27]]},"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The non-metabolised antihistamine fexofenadine has oral absorption resulting from transporter activity. Uptake by enterocyte organic anion transporting polypeptides and efflux by an ATP-binding cassette transporter (P-glycoprotein) are primary determinants. Coeliac disease-mediated lesions to the small intestinal mucosa may alter oral absorption of the drug probe, fexofenadine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A phase I, open-label, single-dose, pharmacokinetic study<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>London, Ontario, Canada<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Patients with coeliac disease (n=41) with positive serology and healthy individuals (n=48).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measures<\/jats:title>\n                    <jats:p>Patients with coeliac disease\u2014duodenal histology and oral fexofenadine pharmacokinetics within a 3-week period. Healthy individuals\u2014oral fexofenadine pharmacokinetics with water and grapefruit juice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with coeliac disease were stratified by disease severity: Group A (n=15, normal), B+C (n=14, intraepithelial lymphocytosis with\/without mild villous blunting) and D (n=12, moderate to severe villous blunting). Patients with coeliac disease in groups A, B+C\u2009and D and healthy individuals receiving water had similar fexofenadine AUC\n                      <jats:sub>0\u20138<\/jats:sub>\n                      (2038\u00b1304, 2259\u00b1367, 2128\u00b1410, 1954\u00b1138\u2009ng.h\/mL; p&gt;0.05; mean\u00b1SEM) and Cmax (440\u00b173, 513\u00b196, 523\u00b1104, 453\u00b132\u2009ng\/mL; p&gt;0.05), respectively. These four groups all had higher fexofenadine AUC\n                      <jats:sub>0\u20138<\/jats:sub>\n                      (1063\u00b159; p&lt;0.01) and Cmax (253\u00b118; p&lt;0.05) compared with those for healthy individuals receiving grapefruit juice. Coeliac groups had a positive linear trend between disease severity and fexofenadine Tmax (2.0\u00b10.3, 2.7\u00b10.4, 3.1\u00b10.5\u2009hours; p&lt;0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Coeliac disease severity based on duodenal histopathology did not affect oral fexofenadine bioavailability. Increased Tmax suggested absorption distal to the duodenum (jejunum + ileum), where histology seems more normal which may be the key determinant. Patients with coeliac disease may not require consideration for alternative clinical drug management for a number of non-metabolised and transport-mediated medications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2021-057151","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T21:15:27Z","timestamp":1677273327000},"page":"e057151","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Severity of coeliac disease and clinical management study when using a non-metabolised medication: a phase I pharmacokinetic study"],"prefix":"10.1136","volume":"13","author":[{"given":"Marc L","family":"Chretien","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9482-2552","authenticated-orcid":false,"given":"David G","family":"Bailey","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada"},{"name":"Lawson Health Research Institute, London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Asher","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy","family":"Parfitt","sequence":"additional","affiliation":[{"name":"Division of Pathology & Laboratory Medicine, Department of Medicine, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Driman","sequence":"additional","affiliation":[{"name":"Division of Pathology & Laboratory Medicine, Department of Medicine, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie","family":"Gregor","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George K","family":"Dresser","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada"},{"name":"Lawson Health Research Institute, London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"2025121510200382000_13.2.e057151.1","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1001\/jama.2017.9730","article-title":"Celiac disease and nonceliac gluten sensitivity: a review","volume":"318","author":"Leonard","year":"2017","journal-title":"JAMA"},{"key":"2025121510200382000_13.2.e057151.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31796-8"},{"key":"2025121510200382000_13.2.e057151.3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41572-018-0054-z","article-title":"Coeliac disease","volume":"5","author":"Lindfors","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"2025121510200382000_13.2.e057151.4","doi-asserted-by":"crossref","unstructured":"Chretien ML , Bailey DG , Asher L , et al . 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