{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:19:26Z","timestamp":1788459566030,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,11,9]],"date-time":"2015-11-09T00:00:00Z","timestamp":1447027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"AstraZeneca Pharmaceuticals LP"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Naloxegol is a PEGylated, oral, peripherally acting \u03bc\u2010opioid receptor antagonist approved in the United States for treatment of opioid\u2010induced constipation in patients with noncancer pain. Naloxegol is metabolized by CYP3A, and its properties as a substrate for the P\u2010glycoprotein (PGP) transporter limit its central nervous system (CNS) permeability. This double\u2010blind, randomized, 2\u2010part, crossover study in healthy volunteers evaluated the effect of quinidine (600\u2009mg PO), a CYP3A\/PGP transporter inhibitor, on the pharmacokinetics and CNS distribution of naloxegol (25\u2009mg PO). In addition, the effects of quinidine on morphine (5\u2009mg\/70\u2009kg IV)\u2010induced miosis and exposure to naloxegol were assessed. Coadministration of quinidine and naloxegol increased naloxegol's AUC 1.4\u2010fold and C<jats:sub>max<\/jats:sub> 2.5\u2010fold but did not antagonize morphine\u2010induced miosis, suggesting that PGP inhibition does not increase the CNS penetration of naloxegol. Naloxegol pharmacokinetics was unaltered by coadministration of morphine and either quinidine or placebo; conversely, pharmacokinetics of morphine and its metabolites (in the presence of quinidine) were unaltered by coadministration of naloxegol. Naloxegol was safe and well tolerated, alone or in combination with quinidine, morphine, or both. The observed increase in exposure to naloxegol in the presence of quinidine is primarily attributed to quinidine's properties as a weak CYP3A inhibitor.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcph.613","type":"journal-article","created":{"date-parts":[[2015,8,6]],"date-time":"2015-08-06T13:09:23Z","timestamp":1438866563000},"page":"497-505","source":"Crossref","is-referenced-by-count":22,"title":["The effect of quinidine, a strong P\u2010glycoprotein inhibitor, on the pharmacokinetics and central nervous system distribution of naloxegol"],"prefix":"10.1002","volume":"56","author":[{"given":"Khanh","family":"Bui","sequence":"first","affiliation":[{"name":"AstraZeneca Pharmaceuticals Waltham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahua","family":"She","sequence":"additional","affiliation":[{"name":"AstraZeneca Pharmaceuticals Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diansong","family":"Zhou","sequence":"additional","affiliation":[{"name":"AstraZeneca Pharmaceuticals Waltham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Butler","sequence":"additional","affiliation":[{"name":"AstraZeneca Pharmaceuticals Wilmington DE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidal","family":"Al\u2010Huniti","sequence":"additional","affiliation":[{"name":"AstraZeneca Pharmaceuticals Waltham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Sostek","sequence":"additional","affiliation":[{"name":"AstraZeneca Pharmaceuticals Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,11,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9610(01)00782-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4637.2008.00495.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.09.019"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2009.01458.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2011.592830"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000165778"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310246"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2013.04.024"},{"key":"e_1_2_7_10_1","unstructured":"Movantik\u2122 (naloxegol). 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Accessed October 27 2014."},{"issue":"4","key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1358\/mf.2004.26.4.831332","article-title":"Pupillometry in the detection of concomitant drug use in opioid\u2010maintained patients","volume":"26","author":"Murillo R","year":"2004","journal-title":"Methods Find Exp Clin Pharmacol"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2011.10111704"},{"key":"e_1_2_7_18_1","unstructured":"BuiK ZhouD SostekM SheF Al\u2010HunitiN.Effects of CYP3A modulators on the pharmacokinetics of naloxegol [poster]. Paper presented at: American Society for Clinical Pharmacology and Therapeutics Annual Meeting; March 18\u201022 2014; Atlanta GA."},{"key":"e_1_2_7_19_1","unstructured":"ZhouD BuiK SostekM Al\u2010HunitiN.A physiologically\u2010based pharmacokinetic (PBPK) model for simulation of naloxegol pharmacokinetics and drug\u2010drug interaction (DDI) potential [poster]. 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