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MNTX in oral immediate\u2010release (MNTX\u2010IR) and extended\u2010release (MNTX\u2010ER) dosage forms may antagonize the opioid induced delay in oro\u2010cecal transit time (OCT) as measured by using radiolabeled lactulose. Because lactulose acts laxative by its own and efficacy of MNTX on colon transit time (CTT) was unknown, the opioid antagonistic effects MNTX\u2010IR and MNTX\u2010ER (both 500\u2009mg) relative to MNTX\u2010SC (12\u2009mg) were evaluated in 15 healthy subjects with loperamide (LOP, 3\u2009\u00d7\u20094\u2009mg, 12\u2009hourly) induced experimental constipation using the sulfasalazine\/sulfapyridine method and radio\u2010opaque markers to measure OCT and whole gut transit time (WGT). MNTX\u2010ER significantly antagonized the LOP effects in 12 of our 15 subjects who responded to LOP with prolongation of WGT by 20.6\u201374.1\u2009h (OCT by 0.50\u201310.5\u2009h, CTT by 18.3\u201373.6\u2009h). MNTX\u2010SC and MNTX\u2010IR were without significant influence. Compared to MNTX\u2010SC, bioavailability of MNTX\u2010IR and MNTX\u2010ER was 1.53\u20135.49\u2009% and 0.11\u20131.24\u2009%, respectively. MNTX\u2010SC and MNTX\u2010IR achieved active serum levels only for \u223c3\u20135\u2009h. MNTX\u2010ER antagonized the opioid\u2010induced delay of CTT most likely by local effects on \u00b5\u2010opioid receptors in the colon.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcph.624","type":"journal-article","created":{"date-parts":[[2015,8,27]],"date-time":"2015-08-27T23:44:52Z","timestamp":1440719092000},"page":"239-245","source":"Crossref","is-referenced-by-count":17,"title":["Extended\u2010release but not immediate\u2010release and subcutaneous methylnaltrexone antagonizes the loperamide\u2010induced delay of whole\u2010gut transit time in healthy subjects"],"prefix":"10.1002","volume":"56","author":[{"given":"Julia","family":"Kolbow","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Center of Drug Absorption and Transport University Medicine Greifswald Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiane","family":"Modess","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Center of 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