{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:58:20Z","timestamp":1791068300972,"version":"4.1.0"},"reference-count":0,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2002,10,22]],"date-time":"2002-10-22T00:00:00Z","timestamp":1035244800000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2002,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Our objective was to examine the effects of itraconazole on the pharmacokinetics and cortisol\u2010suppressant activity of budesonide administered by inhalation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a randomized, double\u2010blind, 2\u2010phase crossover study, 10 healthy subjects took 200 mg itraconazole or placebo orally once a day for 5 days. On day 5, 1 hour after the last dose of itraconazole or placebo, 1000 \u03bcg budesonide was administered by inhalation. Plasma budesonide and cortisol concentrations were measured up to 23 hours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Itraconazole increased the mean total area under the plasma concentration\u2010time curve of inhaled budesonide 4.2\u2010fold (range, 1.7\u2010fold to 9.8\u2010fold; <jats:italic>P<\/jats:italic> &lt; .01) and the peak plasma concentration 1.6\u2010fold (<jats:italic>P<\/jats:italic> &lt; .01) compared with placebo. The mean terminal half\u2010life of budesonide was prolonged from 1.6 to 6.2 hours (ie, 3.7\u2010fold; range, 1.5\u2010fold to 9.3\u2010fold; <jats:italic>P<\/jats:italic> &lt; .001) by itraconazole. The suppression of cortisol production after inhalation of budesonide was significantly increased by itraconazole as compared with placebo, as shown by a 43% reduction in the area under the plasma cortisol concentration\u2010time curve from 0.5 to 10 hours (<jats:italic>P<\/jats:italic> &lt; .001) and a 12% decrease in the cortisol concentration measured 23 hours after administration of budesonide, at 8 am (<jats:italic>P<\/jats:italic> &lt; .05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Itraconazole markedly increased systemic exposure to inhaled budesonide, probably by inhibiting the cytochrome P4503A4\u2010mediated metabolism of budesonide during both the first\u2010pass and the elimination phases. This interaction resulted in enhanced systemic effects of budesonide, as shown by suppression of cortisol production. Long\u2010term coadministration of budesonide and a potent CYP3A4 inhibitor may be associated with an increased risk of adverse effects of budesonide.<\/jats:p><jats:p><jats:italic>Clinical Pharmacology &amp; Therapeutics<\/jats:italic> (2002) <jats:bold>72<\/jats:bold>, 362\u2013369; doi: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1067\/mcp.2002.127397\">10.1067\/mcp.2002.127397<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1067\/mcp.2002.127397","type":"journal-article","created":{"date-parts":[[2002,11,5]],"date-time":"2002-11-05T13:49:19Z","timestamp":1036504159000},"page":"362-369","source":"Crossref","is-referenced-by-count":60,"title":["Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole"],"prefix":"10.1111","volume":"72","author":[{"given":"Kari","family":"Raaska","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology University of Helsinki and Helsinki University Central Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikko","family":"Niemi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University of Helsinki and Helsinki University Central Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikko","family":"Neuvonen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University of Helsinki and Helsinki University Central Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pertti J.","family":"Neuvonen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University of Helsinki and Helsinki University Central Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari T.","family":"Kivist\u00f6","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology University of Helsinki and Helsinki University Central Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,10,22]]},"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1067\/mcp.2002.127397","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T10:03:48Z","timestamp":1700301828000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1067\/mcp.2002.127397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,10]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2002,10]]}},"alternative-id":["10.1067\/mcp.2002.127397"],"URL":"https:\/\/doi.org\/10.1067\/mcp.2002.127397","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,10]]}}}