{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T13:28:10Z","timestamp":1783949290430,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001543","name":"Neurological Foundation of New Zealand","doi-asserted-by":"publisher","award":["1639PG"],"award-info":[{"award-number":["1639PG"]}],"id":[{"id":"10.13039\/501100001543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["18\/063"],"award-info":[{"award-number":["18\/063"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Multiple sclerosis (MS) is a chronic autoimmune disease characterized by central nervous system demyelination, leading to sensory and motor dysfunction. Previous studies have demonstrated that the kappa opioid receptor agonist nalfurafine (Nalf) reduces disease severity and promotes remyelination in the experimental autoimmune encephalomyelitis (EAE) model of MS. However, the pharmacokinetics of Nalf and its optimal administration route for clinical translation remain unexplored. To investigate Nalf's pharmacokinetics and identify an effective oral delivery strategy, we successfully optimized a liquid chromatography\u2013mass spectrometry (LC\u2013MS) method for detecting Nalf in plasma and brain tissues of mice treated via intraperitoneal (ip) or oral administration. Nalf exhibited similar pharmacokinetic profiles following both ip and oral administration, with the oral route achieving almost 70% bioavailability and a longer elimination half\u2010life compared to ip. Nalf effectively reached the brain and significantly reduced a range of disease parameters in EAE in a dose\u2010dependent manner. Our findings demonstrate that oral administration of Nalf is pharmacokinetically favourable and effectively reduces disease disability and promotes remyelination in the EAE model. This study supports the clinical development of oral Nalf as a potential treatment for MS, offering an effective and noninvasive alternative to injections.<\/jats:p>","DOI":"10.1111\/bcpt.70178","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T05:53:45Z","timestamp":1766037225000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development and Application of an LC\u2013MS Method for the Pharmacokinetics and Pharmacodynamics of Oral Therapeutic Efficacy of Nalfurafine"],"prefix":"10.1111","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0568-8997","authenticated-orcid":false,"given":"Sven","family":"Sondhauss","sequence":"first","affiliation":[{"name":"School of Biological Sciences Victoria University of Wellington  Wellington New Zealand"},{"name":"Centre for Biodiscovery Victoria University of Wellington  Wellington New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie","family":"Kiernan","sequence":"additional","affiliation":[{"name":"School of Biological Sciences Victoria University of Wellington  Wellington New Zealand"},{"name":"Centre for Biodiscovery Victoria University of Wellington  Wellington New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Morizzi","sequence":"additional","affiliation":[{"name":"Monash Institute of Pharmaceutical Sciences  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil","family":"Wright","sequence":"additional","affiliation":[{"name":"Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas\u00a0E.","family":"Prisinzano","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bronwyn\u00a0M.","family":"Kivell","sequence":"additional","affiliation":[{"name":"School of Biological Sciences Victoria University of Wellington  Wellington New Zealand"},{"name":"Centre for Biodiscovery Victoria University of Wellington  Wellington New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6638-2679","authenticated-orcid":false,"given":"Katharina","family":"Robichon","sequence":"additional","affiliation":[{"name":"School of Biological Sciences Victoria University of Wellington  Wellington New Zealand"},{"name":"Department of Pathology and Molecular Medicine University of Otago  Wellington New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u00a0Camille","family":"La\u00a0Flamme","sequence":"additional","affiliation":[{"name":"School of Biological Sciences Victoria University of Wellington  Wellington New Zealand"},{"name":"Centre for Biodiscovery Victoria University of Wellington  Wellington New Zealand"},{"name":"Malaghan Institute of Medical Research  Wellington New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(00)00351-9"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1234"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1480"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24583"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2017.01.016"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp588"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2012.693164"},{"key":"e_1_2_13_9_1","volume-title":"Assay Guidance Manual","author":"Chung T. 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