{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T10:48:56Z","timestamp":1768819736771,"version":"3.49.0"},"reference-count":11,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T00:00:00Z","timestamp":1325808000000},"content-version":"vor","delay-in-days":1558,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:p><jats:bold>Study Objective<\/jats:bold>. To evaluate the potential of rifaximin, an oral nonabsorbed (&lt; 0.4%) structural analog of rifampin, to induce human hepatic and\/or intestinal cytochrome P450 (CYP) 3A enzymes, with use of a known CYP3A probe, midazolam.<\/jats:p><jats:p><jats:bold>Design<\/jats:bold>. Prospective, randomized, open\u2010label, two\u2010period, crossover study.<\/jats:p><jats:p><jats:bold>Setting<\/jats:bold>. Clinical research center.<\/jats:p><jats:p><jats:bold>Subjects<\/jats:bold>. Twenty\u2010seven healthy adult volunteers.<\/jats:p><jats:p><jats:bold>Intervention<\/jats:bold>. During the first treatment period, subjects received a single dose of either intravenous midazolam 2 mg over 30 minutes or oral midazolam 6 mg on day 0. From days 3\u201310, they received rifaximin 200 mg every 8 hours. On days 6 (after the 9th dose of rifaximin) and 10 (after the 21st dose of rifaximin), subjects received a concomitant single dose of intravenous or oral midazolam. After a 15\u2010day washout period, subjects were crossed over to the other formulation of midazolam, and the treatment schedule was repeated, with the second treatment period starting on day 26 and single\u2010dose administration of midazolam on days 26, 32, and 36. Serial plasma samples were collected for pharmacokinetic analyses.<\/jats:p><jats:p><jats:bold>Measurements and Main Results<\/jats:bold>. The pharmacokinetic parameters of single\u2010dose intravenous or oral midazolam were determined alone and after coadministration of rifaximin for 3 and 7 days. Rifaximin coadministration did not alter the measured pharmacokinetic parameters for midazolam or its major metabolite, 1\u2032\u2010hydroxymidazolam. The 90% confidence intervals for the maximum concentration and area under the concentration\u2010time curve from time zero extrapolated to infinity (bioavailability) were all within 80\u2013125% for intravenous and oral midazolam. Therefore, no drug interaction was observed between rifaximin and midazolam. Coadministration of midazolam and rifaximin was well tolerated.<\/jats:p><jats:p><jats:bold>Conclusion<\/jats:bold>. Overall, 3\u20137 days of rifaximin 200 mg 3 times\/day did not alter single\u2010dose midazolam pharmacokinetics. Rifaximin also does not appear to induce intestinal or hepatic CYP3A activity.<\/jats:p>","DOI":"10.1592\/phco.27.10.1361","type":"journal-article","created":{"date-parts":[[2007,9,27]],"date-time":"2007-09-27T07:52:53Z","timestamp":1190879573000},"page":"1361-1369","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["The Effect of Multiple\u2010Dose, Oral Rifaximin on the Pharmacokinetics of Intravenous and Oral Midazolam in Healthy Volunteers"],"prefix":"10.1002","volume":"27","author":[{"given":"Helen S.","family":"Pentikis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Connolly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol B.","family":"Trapnell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William P.","family":"Forbes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doug K.","family":"Bettenhausen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,1,6]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/499950"},{"key":"e_1_2_1_3_2","volume-title":"Xifaxan (rifaximin) prescribing information","author":"Salix Pharmaceuticals Inc.","year":"2007"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.162.9.985"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(99)70009-3"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.129068"},{"key":"e_1_2_1_7_2","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1201\/b14095","volume-title":"Pharmacokinetics","author":"Gibaldi M","year":"1982"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050426"},{"key":"e_1_2_1_9_2","first-page":"51","article-title":"Pharmacokinetic study of rifaximin after oral administration in healthy volunteers","volume":"14","author":"Descombe JJ","year":"1994","journal-title":"Int J Clin Pharmacol Res"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.1999.00553.x"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2003.11.366"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026648812439"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1592%2Fphco.27.10.1361","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1592\/phco.27.10.1361","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T11:45:48Z","timestamp":1761047148000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1592\/phco.27.10.1361"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,10]]},"references-count":11,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2007,10]]}},"alternative-id":["10.1592\/phco.27.10.1361"],"URL":"https:\/\/doi.org\/10.1592\/phco.27.10.1361","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,10]]},"assertion":[{"value":"2012-01-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}