{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T03:22:42Z","timestamp":1780543362577,"version":"3.54.1"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T00:00:00Z","timestamp":1510185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Opioid\u2010induced constipation (<jats:styled-content style=\"fixed-case\">OIC<\/jats:styled-content>) is a major side effect of opioid use. Centrally acting antagonists result in opioid withdrawal or worsening of pain and lead to use of peripherally acting mu\u2010opioid receptor antagonists (<jats:styled-content style=\"fixed-case\">PAMORA<\/jats:styled-content>s). The required doses of the <jats:styled-content style=\"fixed-case\">PAMORA<\/jats:styled-content>s, methylnaltrexone and naloxegol, in the treatment of <jats:styled-content style=\"fixed-case\">OIC<\/jats:styled-content> are well established in chronic opioid users. <jats:styled-content style=\"fixed-case\">OIC<\/jats:styled-content> may occur after short duration of opioid treatment; the required doses of naloxone, naltrexone, and <jats:styled-content style=\"fixed-case\">PAMORA<\/jats:styled-content>s in opioid\u2010na\u00efve subjects (with no opioid use for at least 3\u00a0months) are unclear. The aim of this review was to evaluate the <jats:styled-content style=\"fixed-case\">PAMORA<\/jats:styled-content> dose required for opioid\u2010na\u00efve subjects to achieve similar beneficial effects on symptoms or valid surrogates to those observed in chronic opioid users.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A PubMed search of \u03bc\u2010opioid antagonists to counter \u03bc\u2010opioid effects included terms: naloxone, naltrexone, methylnaltrexone, alvimopan, and naloxegol, as well as <jats:styled-content style=\"fixed-case\">OIC<\/jats:styled-content> and colonic transit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The approved dose of methylnaltrexone in chronic opioid users, 0.3\u00a0mg\/kg subcutaneous (<jats:styled-content style=\"fixed-case\">SQ<\/jats:styled-content>), did not affect motility in opioid\u2010na\u00efve subjects. Trials investigating the required dose of alvimopan showed 0.5\u20101\u00a0mg dose was efficacious in treating <jats:styled-content style=\"fixed-case\">OIC<\/jats:styled-content>; a 10\u2010fold higher dose (12\u00a0mg) of alvimopan is needed to block effects of codeine on small bowel and colonic transit in opioid\u2010na\u00efve subjects compared to chronic opioid users. Opioid\u2010na\u00efve users need 125\u00a0mg of naloxegol to reverse the effects of opioids on transit; this is in contrast to the 12.5 to 25\u00a0mg needed to treat <jats:styled-content style=\"fixed-case\">OIC<\/jats:styled-content> in chronic opioid users.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Opioid\u2010na\u00efve subjects require a higher dose of <jats:styled-content style=\"fixed-case\">PAMORA<\/jats:styled-content> than chronic opioid users to achieve \u03bc\u2010opioid antagonist effect.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13250","type":"journal-article","created":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T06:12:41Z","timestamp":1510207961000},"source":"Crossref","is-referenced-by-count":6,"title":["Insights on efficacious doses of <scp>PAMORA<\/scp>s for patients on chronic opioid therapy or opioid\u2010na\u00efve patients"],"prefix":"10.1111","volume":"30","author":[{"given":"K.","family":"van Malderen","sequence":"first","affiliation":[{"name":"Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Halawi","sequence":"additional","affiliation":[{"name":"Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6472-7514","authenticated-orcid":false,"given":"M.","family":"Camilleri","sequence":"additional","affiliation":[{"name":"Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-3150.2004.00554.x"},{"key":"e_1_2_9_3_1","unstructured":"WorldHealthOrganization.Cancer Pain Relief. Geneva:World Health Organization;1986:74."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1507771"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.99B7.BJJ-2016-1350.R1"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/pm\/pnw255"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(88)90673-7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-017-0560-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-012-1494-8"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/BCR.0b013e31829b399d"},{"key":"e_1_2_9_11_1","first-page":"1347","article-title":"Management of common opioid\u2010induced adverse effects","volume":"74","author":"Swegle JM","year":"2006","journal-title":"Am Fam Physician"},{"key":"e_1_2_9_12_1","first-page":"2407","article-title":"Constipation in people prescribed opioids","volume":"4","author":"Ahmedzai SH","year":"2010","journal-title":"BMJ Clin Evid"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-013-0102-0"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2012.05040.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2011.563236"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2007.00944.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9610(01)00783-8"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1K009"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0707377"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/papr.12535"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(97)90197-1"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2010.04422.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2016.01.027"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2007.11.008"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2010.06.013"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2010.06.012"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-3565(05)00434-9"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.116.239061"},{"key":"e_1_2_9_29_1","first-page":"1210","article-title":"Evaluation of single oral doses of NKTR\u2010118 (PEG\u2010Naloxol) as an oral peripheral opioid antagonist in healthy male subjects","volume":"47","author":"Neumann T","year":"2007","journal-title":"J Clin Pharmacol"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310246"},{"key":"e_1_2_9_31_1","first-page":"S230","article-title":"A phase I, randomized, double\u2010blind, placebo\u2010controlled study of the effects of naloxegol on gastric, small bowel, and colonic transit in healthy subjects receiving codeine or placebo","volume":"112","author":"Halawi H","year":"2017","journal-title":"Am J Gastroenterol"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnmo.13250","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.13250","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T15:04:37Z","timestamp":1695481477000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.13250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,9]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1111\/nmo.13250"],"URL":"https:\/\/doi.org\/10.1111\/nmo.13250","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,9]]},"article-number":"e13250"}}