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This is a prospective, single\u2010center, observational study aimed to evaluate the influence of genetic polymorphisms and cachexia status on plasma naldemedine and clinical responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Forty\u2010eight patients being treated with naldemedine for opioid\u2010induced constipation under treatment of cancer pain were enrolled. Plasma naldemedine concentrations were determined on the fourth day or later after administration of naldemedine, and the associations with genotypes, cachexia status, and clinical responses were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cancer patients exhibited a large variation in the plasma naldemedine concentrations, and it was correlated with serum total protein level. Patients who were homozygous <jats:italic>CYP3A5*3<\/jats:italic> had a higher plasma concentration of naldemedine than those with the <jats:italic>*1<\/jats:italic> allele. ABCB1 genotypes tested in this study were not associated with plasma naldemedine. A negative correlation was observed between the plasma naldemedine concentration and 4\u03b2\u2010hydroxycholesterol level. The plasma naldemedine concentration was lower in patients with refractory cachexia than in those with precachexia and cachexia. While serum levels of interleukin\u20106 (IL\u20106) and acute\u2010phase proteins were higher in patients with refractory cachexia, they were not associated with plasma naldemedine. A higher plasma concentration of naldemedine, <jats:italic>CYP3A5*3\/*3<\/jats:italic>, and an earlier naldemedine administration after starting opioid analgesics were related to improvement of bowel movements.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Plasma naldemedine increased under deficient activity of CYP3A5 in cancer patients. Cachectic patients with a higher serum IL\u20106 had a lower plasma naldemedine. Plasma naldemedine, related to CYP3A5 genotype, and the initiation timing of naldemedine were associated with improved bowel movements.<\/jats:p><\/jats:sec>","DOI":"10.1111\/fcp.12976","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T07:38:20Z","timestamp":1704785900000},"page":"596-605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Impacts of genetic polymorphisms and cancer cachexia on naldemedine pharmacokinetics and bowel movements in patients receiving opioid analgesics"],"prefix":"10.1111","volume":"38","author":[{"given":"Emi","family":"Nakatsugawa","sequence":"first","affiliation":[{"name":"Department of Hospital Pharmacy Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7447-3789","authenticated-orcid":false,"given":"Takafumi","family":"Naito","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Hamamatsu University School of Medicine  Hamamatsu Japan"},{"name":"Department of Pharmacy Shinshu University Hospital  Matsumoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaito","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Hamamatsu University School of Medicine  Hamamatsu Japan"},{"name":"Department of Pharmacy Shinshu University Hospital  Matsumoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Kitajima","sequence":"additional","affiliation":[{"name":"Division of Palliative Care Center Hamamatsu University Hospital  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,8]]},"reference":[{"issue":"1","key":"e_1_2_10_2_1","first-page":"62","article-title":"Methylnaltrexone: peripherally acting \u03bc\u2010opioid receptor antagonist","volume":"10","author":"Uritsky TJ","year":"2019","journal-title":"J Adv Pract Oncol"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.09.019"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310246"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526\u20104637.2008.00495.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.70.8453"},{"key":"e_1_2_10_7_1","unstructured":"Product information for Symproic. 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