{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T12:41:35Z","timestamp":1697460095693},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,7,19]],"date-time":"2005-07-19T00:00:00Z","timestamp":1121731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2005,11]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Dexloxiglumide is a new CCK<jats:sub>1<\/jats:sub> receptor antagonist under investigation for treatment of functional gastrointestinal disorders and is metabolized by CYP3A4 and CYP2C9. The objectives of these two separate randomized, two\u2010period, two\u2010treatment crossover studies were to investigate the effects of steady\u2010state ketoconazole, a model CYP3A4 inhibitor (Study\u20031), and steady\u2010state fluconazole, a model CYP2C9 inhibitor (Study\u20032), on the pharmacokinetics of dexloxiglumide in healthy subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Plasma samples were analysed for dexloxiglumide and its primary metabolites: O\u2010demethyl dexloxiglumide (ODM; Study\u20031 and 2) and dexloxiglumide carboxylic acid (DCA; Study\u20032).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Following ketoconazole coadministration, dexloxiglumide <jats:italic>C<\/jats:italic><jats:sub><jats:italic>max<\/jats:italic><\/jats:sub> increased by 32% (90% confidence intervals (CI) 112\u2013154), with unchanged ODM <jats:italic>C<\/jats:italic><jats:sub><jats:italic>max<\/jats:italic><\/jats:sub>; AUC of dexloxiglumide and ODM increased by 36% (90%\u2003CI 124\u2013140 and 128\u2013142, respectively). No changes were observed in dexloxiglumide or ODM <jats:italic>t<\/jats:italic><jats:sub>\u00bd<\/jats:sub>. Fluconazole coadministration caused a 77% increase (90%\u2003CI 154\u2013204) in dexloxiglumide <jats:italic>C<\/jats:italic><jats:sub><jats:italic>max<\/jats:italic><\/jats:sub>, no change in ODM <jats:italic>C<\/jats:italic><jats:sub><jats:italic>max<\/jats:italic><\/jats:sub> and a 32% decrease (90%\u2003CI 62\u201375) in DCA <jats:italic>C<\/jats:italic><jats:sub><jats:italic>max<\/jats:italic><\/jats:sub>. Fluconazole coadministration resulted in a 2.5\u2010fold increase (90%\u2003CI 235\u2013267) in dexloxiglumide AUC, 40% increase (90%\u2003CI 136\u2013156) in ODM AUC and an 18% decrease (90%\u2003CI 82\u201394) in DCA AUC. The <jats:italic>t<\/jats:italic><jats:sub>\u00bd<\/jats:sub> of all three analytes increased by approximately 2\u2010fold with fluconazole coadministration (<jats:italic>P<\/jats:italic>\u2010value &lt;\u200a0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Ketoconazole caused a minimal increase while fluconazole caused a moderate increase in dexloxiglumide systemic exposure with no change in the adverse event profile of dexloxiglumide.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2005.02465.x","type":"journal-article","created":{"date-parts":[[2005,10,19]],"date-time":"2005-10-19T09:23:14Z","timestamp":1129713794000},"page":"498-507","source":"Crossref","is-referenced-by-count":8,"title":["Effect of azole antifungals ketoconazole and fluconazole on the pharmacokinetics of dexloxiglumide"],"prefix":"10.1111","volume":"60","author":[{"given":"Abhijeet S.","family":"Jakate","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Partha","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alpita","family":"Patel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wattanaporn","family":"Abramowitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Persiani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Wangsa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ram","family":"Kapil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,7,27]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"703","article-title":"Pharmacological characterisation of a new potent and specific nonpolypeptidic cholecystokinin antagonist","volume":"37","author":"Setnikar I","year":"1987","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0196-9781(94)90104-X"},{"key":"e_1_2_6_4_2","first-page":"695","volume-title":"Physiology of the gastrointestinal tract.","author":"Ryan J","year":"1987"},{"key":"e_1_2_6_5_2","first-page":"403","volume-title":"The Pancreas: biology pathobiology, disease","author":"Chey W","year":"1993"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1994.tb44065.x"},{"key":"e_1_2_6_7_2","doi-asserted-by":"crossref","first-page":"1334S","DOI":"10.1093\/jn\/124.suppl_8.1334S","article-title":"Role of cholecystokinin in the regulation of gastrointestinal motility","volume":"124","author":"Grider JR","year":"1994","journal-title":"J Nutr"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0928-4257(93)90035-R"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.11.6917"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.1610"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90024-H"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.5414\/CPP40198"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.397"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200038020-00002"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.1.160-165.2002"},{"key":"e_1_2_6_16_2","first-page":"610","article-title":"Formation of (R)\u20108\u2010hydroxywarfarin in human liver microsomes. 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