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The base model was empirically adapted to patients with primary biliary cirrhosis (PBC) based on current understanding of disease pathophysiology and clinical measurements. Simulations were performed for patients with PBC under two competing hypotheses: one for inhibition of ileal absorption of both UDCA and conjugates and the other only of conjugates. The simulations predicted distinctly different bile acid distribution patterns in plasma and bile. The UDCA model adapted to patients with PBC provides a platform to investigate a complex therapeutic drug interaction among UDCA, UDCA conjugates, and inhibition of ileal bile acid transport in this rare disease population.<\/jats:p>","DOI":"10.1002\/psp4.12100","type":"journal-article","created":{"date-parts":[[2016,8,18]],"date-time":"2016-08-18T14:02:49Z","timestamp":1471528969000},"page":"418-426","source":"Crossref","is-referenced-by-count":6,"title":["A Systems Model for Ursodeoxycholic Acid Metabolism in Healthy and Patients With Primary Biliary Cirrhosis"],"prefix":"10.1002","volume":"5","author":[{"given":"P","family":"Zuo","sequence":"first","affiliation":[{"name":"PAREXEL International, Durham  North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"RL","family":"Dobbins","sequence":"additional","affiliation":[{"name":"Cempra Pharmaceuticals Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"RL","family":"O'Connor\u2010Semmes","sequence":"additional","affiliation":[{"name":"PAREXEL International, Durham  North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MA","family":"Young","sequence":"additional","affiliation":[{"name":"PAREXEL International, Durham  North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,8,18]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0034-1383731"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.02.014"},{"key":"e_1_2_8_3_1","volume-title":"A comparative study of steroids with special reference to bile salts","author":"Tammar A.R.","year":"1970"},{"key":"e_1_2_8_4_1","volume-title":"The Biological Utility of Bile Salts","author":"Haslewood G.A.D.","year":"1978"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)35109-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)91610-2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(97)70183-5"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4939-1013-7","volume-title":"Cholestatic liver disease","author":"Carey E.J.","year":"2014"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26365"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.12.005"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22428"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.12.029"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.12"},{"key":"e_1_2_8_14_1","unstructured":"Clinicaltrials.gov. 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