{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:53:28Z","timestamp":1791186808044,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,3,15]],"date-time":"2015-03-15T00:00:00Z","timestamp":1426377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:p>The functional impact of altered drug transport protein expression on the systemic pharmacokinetics of morphine, hepatically derived morphine glucuronide (morphine\u20103\u2010 and morphine\u20106\u2010glucuronide), and fasting bile acids was evaluated in patients with biopsy\u2010confirmed nonalcoholic steatohepatitis (NASH) compared to healthy subjects. The maximum concentration (C<jats:sub>max<\/jats:sub>) and area under the concentration\u2010time curve (AUC<jats:sub>0\u2010last<\/jats:sub>) of morphine glucuronide in serum were increased in NASH patients (343 vs. 225 nM and 58.8 vs. 37.2 \u00b5M*min, respectively; <jats:italic>P<\/jats:italic>\u2009\u2264\u20090.005); morphine pharmacokinetics did not differ between groups. Linear regression analyses detected an association of NASH severity with increased morphine glucuronide C<jats:sub>max<\/jats:sub> and AUC<jats:sub>0\u2010last<\/jats:sub> (<jats:italic>P &lt;<\/jats:italic> 0.001). Fasting serum glycocholate, taurocholate, and total bile acid concentrations were associated with NASH severity (<jats:italic>P &lt;<\/jats:italic> 0.006). Increased hepatic basolateral efflux of morphine glucuronide and bile acids is consistent with altered hepatic transport protein expression in patients with NASH and may partially explain differences in efficacy and\/or toxicity of some highly transported anionic drugs\/metabolites in this patient population.<\/jats:p>","DOI":"10.1002\/cpt.66","type":"journal-article","created":{"date-parts":[[2015,3,15]],"date-time":"2015-03-15T13:35:01Z","timestamp":1426426501000},"page":"419-427","source":"Crossref","is-referenced-by-count":77,"title":["Altered morphine glucuronide and bile acid disposition in patients with nonalcoholic steatohepatitis"],"prefix":"10.1111","volume":"97","author":[{"given":"BC","family":"Ferslew","sequence":"first","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CK","family":"Johnston","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Tsakalozou","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AS","family":"Bridges","sequence":"additional","affiliation":[{"name":"Department of Pathology, UNC School of Medicine University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MF","family":"Paine","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Jia","sequence":"additional","affiliation":[{"name":"Metabolomics Shared Resource University of Hawaii Cancer Center Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PW","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, UNC Gillings School of Global Public Health University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"IV","given":"AS","family":"Barritt","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, UNC School of Medicine University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KLR","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,15]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.04.001"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20466"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.09.038"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24558"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2013.06.024"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907929"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1872-034X.2012.01034.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.78"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.79"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.113.055558"},{"key":"e_1_2_10_11_1","first-page":"e20","article-title":"Effect of ritonavir on (99m) technetium\u2010mebrofenin disposition in humans: a semi\u2010PBPK modeling and in vitro approach to predict transporter\u2010mediated DDIs. 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