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Continuous 12\u2010lead electrocardiogram (<jats:styled-content style=\"fixed-case\">EKG<\/jats:styled-content>), heart rate, blood pressure, and respiratory rate were monitored, and pharmacokinetic parameters from the three visits were compared. The peak plasma concentration (C<jats:sub>max<\/jats:sub>) of midazolam increased by 66% and 71% at 3\u2010 and 12\u2010month post\u2010<jats:styled-content style=\"fixed-case\">RYGB<\/jats:styled-content> (p=0.017 and p=0.001, respectively), whereas the median time to peak concentration (T<jats:sub>max<\/jats:sub>) was reduced by 50%. The mean C<jats:sub>max<\/jats:sub> for 1\u2032\u2010hydroxymidazolam increased by 87% and 80% at 3 and 12 months (p=0.001 and p&lt;0.001, respectively). However, neither the area under the concentration\u2010time curve (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>) for midazolam nor the metabolite\u2010to\u2010parent <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content> ratio changed significantly over time. For digoxin, the median T<jats:sub>max<\/jats:sub> decreased from 40\u00a0minutes at baseline to 30 and 20\u00a0minutes at 3 and 12 months, respectively. The mean <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content> for digoxin, heart rate, and <jats:styled-content style=\"fixed-case\">EKG<\/jats:styled-content> patterns were similar across the three study phases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Contemporary proximal <jats:styled-content style=\"fixed-case\">RYGB<\/jats:styled-content> increases the rate of drug absorption without significantly changing the overall exposure to midazolam and digoxin. The C<jats:sub>max<\/jats:sub> of a <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4 substrate with a high extraction ratio was substantially increased after <jats:styled-content style=\"fixed-case\">RYGB<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.1560","type":"journal-article","created":{"date-parts":[[2015,3,10]],"date-time":"2015-03-10T04:01:54Z","timestamp":1425960114000},"page":"361-369","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Proximal Roux\u2010en\u2010Y Gastric Bypass Alters Drug Absorption Pattern But Not Systemic Exposure of <scp>CYP<\/scp>3A4 and P\u2010glycoprotein Substrates"],"prefix":"10.1002","volume":"35","author":[{"given":"Lingtak\u2010Neander","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Pharmacy School of Pharmacy University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne S.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica C.","family":"Tay\u2010Sontheimer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy","family":"Trawick","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brant K.","family":"Oelschlager","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of General Surgery School of Medicine University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Flum","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of General Surgery School of Medicine University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen K.","family":"Patton","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Cardiology School of Medicine University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny D.","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy School of Pharmacy University of Washington Seattle Washington"},{"name":"Department of Pharmaceutics School of Pharmacy University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Horn","sequence":"additional","affiliation":[{"name":"Department of Pharmacy School of Pharmacy University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2013.3654"},{"key":"e_1_2_6_3_1","first-page":"2416","article-title":"Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity","volume":"310","author":"Courcoulas AP","year":"2013","journal-title":"JAMA"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/annotation\/88dbb5b7\u20103f7e\u20104b26\u2010a5b6\u2010f020d33f0182"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112082"},{"key":"e_1_2_6_6_1","unstructured":"How many bariatric surgeries are taking place?Available fromhttp:\/\/www.amednews.com\/assets\/pdf\/2012gbisa0423b.pdf. 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