{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:47:40Z","timestamp":1787014060999,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    It remains uncertain whether pharmacokinetic changes following Roux\u2010en\u2010Y gastric bypass (RYGB) can be attributed to surgery\u2010induced gastrointestinal alterations per se and\/or the subsequent weight loss. The aim was to compare short\u2010 and long\u2010term effects of RYGB and calorie restriction on CYP3A\u2010activity, and cross\u2010sectionally compare CYP3A\u2010activity with normal weight to overweight controls using midazolam as probe drug. This three\u2010armed controlled trial included patients with severe obesity preparing for RYGB (\n                    <jats:italic>n\u00a0<\/jats:italic>\n                    =\u00a041) or diet\u2010induced (\n                    <jats:italic>n\u00a0<\/jats:italic>\n                    =\u00a041) weight\u2010loss, and controls (\n                    <jats:italic>n\u00a0<\/jats:italic>\n                    =\u00a018). Both weight\u2010loss groups underwent a 3\u2010week low\u2010energy\u2010diet (&lt;1200\u00a0kcal\/day) followed by a 6\u2010week very\u2010low\u2010energy\u2010diet or RYGB (both &lt;800\u00a0kcal\/day). Patients were followed for 2\u00a0years, with four pharmacokinetic investigations using semisimultaneous oral and intravenous dosing to determine changes in midazolam absolute bioavailability and clearance, within and between groups. The RYGB and diet groups showed similar weight\u2010loss at week 9 (13\u00a0\u00b1\u00a02.4% vs. 11\u00a0\u00b1\u00a03.6%), but differed substantially after 2\u00a0years (\u221230\u00a0\u00b1\u00a07.0% vs. \u22123.1\u00a0\u00b1\u00a06.3%). At baseline, mean absolute bioavailability and clearance of midazolam were similar in the RYGB and diet groups, but higher compared with controls. On average, absolute bioavailability was unaltered at week 9, but decreased by 40\u00a0\u00b1\u00a07.5% in the RYGB group and 32\u00a0\u00b1\u00a06.1% in the diet group at year 2 compared with baseline, with no between\u2010group difference. No difference in clearance was observed over time, nor between groups. In conclusion, neither RYGB per se nor weight loss impacted absolute bioavailability or clearance of midazolam short term. Long term, absolute bioavailability was similarly decreased in both groups despite different weight loss, suggesting that the recovered CYP3A\u2010activity is not only dependent on weight\u2010loss through RYGB.\n                  <\/jats:p>","DOI":"10.1111\/cts.13142","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T07:11:19Z","timestamp":1629961879000},"page":"221-233","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Short\u2010 and long\u2010term effects of body weight loss following calorie restriction and gastric bypass on CYP3A\u2010activity \u2013 a non\u2010randomized three\u2010armed controlled trial"],"prefix":"10.1111","volume":"15","author":[{"given":"Kine Eide","family":"Kvitne","sequence":"first","affiliation":[{"name":"Section for Pharmacology and Pharmaceutical Biosciences Department of Pharmacy University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Robertsen","sequence":"additional","affiliation":[{"name":"Section for Pharmacology and Pharmaceutical Biosciences Department of Pharmacy University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Skovlund","sequence":"additional","affiliation":[{"name":"Department of Public Health and Nursing Norwegian University of Science and Technology, NTNU  Trondheim Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hege","family":"Christensen","sequence":"additional","affiliation":[{"name":"Section for Pharmacology and Pharmaceutical Biosciences Department of Pharmacy University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Krogstad","sequence":"additional","affiliation":[{"name":"Section for Pharmacology and Pharmaceutical Biosciences Department of Pharmacy University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Wegler","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Uppsala University  Uppsala Sweden"},{"name":"DMPK, Research and Early Development, Cardiovascular, Renal and Metabolism BioPharmaceuticals R&amp;D, AstraZeneca  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip Carlo","family":"Angeles","sequence":"additional","affiliation":[{"name":"Vestfold Hospital Trust The Morbid Obesity Center  T\u00f8nsberg Norway"},{"name":"Department of Surgery Vestfold Hospital Trust  T\u00f8nsberg Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit Malene","family":"Wollmann","sequence":"additional","affiliation":[{"name":"Center for Psychopharmacology Diakonhjemmet Hospital  Oslo 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Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Late\u2010stage Development, Cardiovascular, Renal and Metabolism BioPharmaceuticals R&amp;D, AstraZeneca  M\u00f6lndal Sweden"},{"name":"Department of Molecular and Clinical Medicine Institute of Medicine Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Andersson","sequence":"additional","affiliation":[{"name":"Research and Early Development, Discovery Sciences BioPharmaceuticals R&amp;D, AstraZeneca  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommy B.","family":"Andersson","sequence":"additional","affiliation":[{"name":"DMPK, Research and Early Development, Cardiovascular, Renal and Metabolism BioPharmaceuticals R&amp;D, AstraZeneca  M\u00f6lndal 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