{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T10:34:42Z","timestamp":1761561282162},"reference-count":34,"publisher":"Wiley","issue":"11-12","license":[{"start":{"date-parts":[[2008,9,19]],"date-time":"2008-09-19T00:00:00Z","timestamp":1221782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Background\u2002<\/jats:bold> Constipation is a significant side effect of opioid therapy. We have previously demonstrated that naloxone\u20103\u2010glucuronide (NX3G) antagonizes the motility\u2010lowering\u2010effect of morphine in the rat colon.<\/jats:p><jats:p><jats:bold>Aim\u2002<\/jats:bold> To find out whether oral NX3G is able to reduce the morphine\u2010induced delay in colonic transit time (CTT) without being absorbed and influencing the analgesic effect.<\/jats:p><jats:p><jats:bold>Methods\u2002<\/jats:bold> Fifteen male volunteers were included. Pharmacokinetics: after oral administration of 0.16\u2003mg\/kg NX3G, blood samples were collected over a 6\u2010h period. Pharmacodynamics: NX3G or placebo was then given at the start time and every 4\u2003h thereafter. Morphine (0.05\u2003mg\/kg) or placebo was injected s.c. 2\u2003h after starting and thereafter every 6\u2003h for 24\u2003h. CTT was measured over a 48\u2010h period by scintigraphy. Pressure pain threshold tests were performed.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> Neither NX3G nor naloxone was detected in the venous blood. The slowest transit time was observed during the morphine phase, which was significantly different from morphine with NX3G and placebo. The pain perception was not significantly influenced by NX3G.<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> Orally administered NX3G is able to reverse the morphine\u2010induced delay of CTT in humans without being detected in peripheral blood samples. Therefore, NX3G may improve symptoms of constipation in\u2010patients using opioid medication without affecting opioid\u2010analgesic effects.<\/jats:p>","DOI":"10.1111\/j.1365-2036.2008.03855.x","type":"journal-article","created":{"date-parts":[[2008,9,19]],"date-time":"2008-09-19T05:53:52Z","timestamp":1221803632000},"page":"1334-1341","source":"Crossref","is-referenced-by-count":11,"title":["The effect of naloxone\u20103\u2010glucuronide on colonic transit time in healthy men after acute morphine administration: a placebo\u2010controlled double\u2010blinded crossover preclinical volunteer study"],"prefix":"10.1111","volume":"28","author":[{"given":"P.","family":"NETZER","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"SENDENSKY","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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