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This study aimed to predict effects of rifampin\u2010mediated intestinal P\u2010glycoprotein (Pgp) induction on pharmacokinetics of Pgp substrates via <jats:styled-content style=\"fixed-case\">PBPK<\/jats:styled-content> modeling. First, we selected four Pgp substrates (digoxin, talinolol, quinidine, and dabigatran etexilate) to derive <jats:italic>in vitro<\/jats:italic> to <jats:italic>in vivo<\/jats:italic> scaling factors for intestinal Pgp kinetics. Assuming unbound\u00a0Michaelis\u2010Menten constant (<jats:italic>K<\/jats:italic><jats:sub>m<\/jats:sub>) to be intrinsic, we focused on the scaling factors for\u00a0maximal efflux rate (J<jats:sub>max<\/jats:sub>) to adequately recover clinically observed results. Next, we predicted rifampin\u2010mediated fold increases in intestinal Pgp abundances to reasonably recover clinically observed <jats:styled-content style=\"fixed-case\">DDI<\/jats:styled-content> results. The modeling results suggested that threefold to fourfold increases in intestinal Pgp abundances could sufficiently reproduce the <jats:styled-content style=\"fixed-case\">DDI<\/jats:styled-content> results of these Pgp substrates with rifampin. Hence, the obtained fold increases can potentially be applicable to <jats:styled-content style=\"fixed-case\">DDI<\/jats:styled-content> prediction with other Pgp substrates.<\/jats:p>","DOI":"10.1002\/psp4.12458","type":"journal-article","created":{"date-parts":[[2019,8,17]],"date-time":"2019-08-17T06:38:23Z","timestamp":1566023903000},"page":"634-642","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Physiologically\u2010Based Pharmacokinetic Modeling Approach to Predict Rifampin\u2010Mediated Intestinal P\u2010Glycoprotein Induction"],"prefix":"10.1002","volume":"8","author":[{"given":"Shinji","family":"Yamazaki","sequence":"first","affiliation":[{"name":"Pharmacokinetics, Dynamics and Metabolism Pfizer Worldwide Research &amp; Development San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chester","family":"Costales","sequence":"additional","affiliation":[{"name":"Pharmacokinetics, Dynamics and Metabolism Pfizer Worldwide Research &amp; Development Groton Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Lazzaro","sequence":"additional","affiliation":[{"name":"Pharmacokinetics, Dynamics and Metabolism Pfizer Worldwide Research &amp; Development Groton Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soraya","family":"Eatemadpour","sequence":"additional","affiliation":[{"name":"Pharmacokinetics, Dynamics and Metabolism Pfizer Worldwide Research &amp; Development Groton Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emi","family":"Kimoto","sequence":"additional","affiliation":[{"name":"Pharmacokinetics, Dynamics and Metabolism Pfizer Worldwide Research &amp; Development Groton Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manthena V.","family":"Varma","sequence":"additional","affiliation":[{"name":"Pharmacokinetics, Dynamics and Metabolism Pfizer Worldwide Research &amp; Development Groton Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,9,5]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2015.10.010"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1081\/DMR-120001389"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161211797440186"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.1.4.641"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.195"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.116.070011"},{"key":"e_1_2_10_7_1","unstructured":"CHMP.Guideline on the investigation of drug interactions<http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2012\/07\/WC500129606.pdf. 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