{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:59:51Z","timestamp":1787313591749,"version":"build-2736575974"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,4,16]],"date-time":"2016-04-16T00:00:00Z","timestamp":1460764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:p>\n                    Naloxegol, a peripherally acting \u03bc\u2010opioid receptor antagonist for the treatment of opioid\u2010induced constipation, is a substrate for cytochrome P450 (CYP) 3A4\/3A5 and the P\u2010glycoprotein (P\u2010gp) transporter. By integrating\n                    <jats:italic>in silico<\/jats:italic>\n                    , preclinical, and clinical pharmacokinetic (PK) findings, minimal and full physiologically based pharmacokinetic (PBPK) models were developed to predict the drug\u2010drug interaction (DDI) potential for naloxegol. The models reasonably predicted the observed changes in naloxegol exposure with ketoconazole (increase of 13.1\u2010fold predicted vs. 12.9\u2010fold observed), diltiazem (increase of 2.8\u2010fold predicted vs. 3.4\u2010fold observed), rifampin (reduction of 76% predicted vs. 89% observed), and quinidine (increase of 1.2\u2010fold predicted vs. 1.4\u2010fold observed). The moderate CYP3A4 inducer efavirenz was predicted to reduce naloxegol exposure by \u223c50%, whereas weak CYP3A inhibitors were predicted to minimally affect exposure. In summary, the PBPK models reasonably estimated interactions with various CYP3A modulators and can be used to guide dosing in clinical practice when naloxegol is coadministered with such agents.\n                  <\/jats:p>","DOI":"10.1002\/psp4.12070","type":"journal-article","created":{"date-parts":[[2016,4,16]],"date-time":"2016-04-16T05:12:46Z","timestamp":1460783566000},"page":"250-257","source":"Crossref","is-referenced-by-count":36,"title":["Simulation and Prediction of the Drug\u2010Drug Interaction Potential of Naloxegol by Physiologically Based Pharmacokinetic Modeling"],"prefix":"10.1002","volume":"5","author":[{"given":"D","family":"Zhou","sequence":"first","affiliation":[{"name":"AstraZeneca Pharmaceuticals Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Bui","sequence":"additional","affiliation":[{"name":"AstraZeneca Pharmaceuticals Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Sostek","sequence":"additional","affiliation":[{"name":"AstraZeneca Pharmaceuticals Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Al\u2010Huniti","sequence":"additional","affiliation":[{"name":"AstraZeneca Pharmaceuticals Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,16]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310246"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2013.04.024"},{"key":"e_1_2_9_3_1","unstructured":"Movantik\u2122 (naloxegol) [package insert]. 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