{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:08:55Z","timestamp":1784099335656,"version":"3.55.0"},"reference-count":18,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Fluorescence\u2010guided surgery enhances intraoperative visualization of anatomical structures. Nizaracianine is a near\u2010infrared fluorescent agent that is exclusively renally cleared in animal models. It enables real\u2010time ureteral imaging and identification, potentially reduces risk of injury and facilitates assessment before surgical closure. While a single dose has shown to be safe, repeated administration may be necessary during prolonged abdominopelvic procedures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This Phase 1 study evaluated the safety, pharmacokinetics and fluorescence properties of repeated nizaracianine dosing in healthy volunteers. Participants received three doses at 0, 1 and 2\u2009h across four dose cohorts: 3\u2009\u00d7\u20090.5, 3\u2009\u00d7\u20091.0, 3\u2009\u00d7\u20092.5 and 3\u2009\u00d7\u20095.0\u2009mg. Safety assessments included vital signs, electrocardiography and laboratory testing. Plasma and urine samples were collected to determine pharmacokinetics. A Foley catheter was used for urine collection and measurement of fluorescence intensity over time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010one participants were included in the final analysis. Thirty\u2010six adverse events were reported, mostly related to catheter placement. Nine events were possibly related to nizaracianine. In all cohorts, geometric means of\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>Max Plasma<\/jats:sub>\n                      (61.83, 122.9, 249.2 and 625.7), AUC\n                      <jats:sub>all<\/jats:sub>\n                      (137.0, 276.9, 694.9 and 1835) and half\u2010life (1.53, 1.52, 1.74 and 1.82) increased, suggesting dose proportionality. Cumulative renal clearance was 65%, indicating possible non\u2010renal clearance pathways. Fluorescence signals were observed in all cohorts within 5\u2009min of administration, persisting up to 8\u2009h after the first dose.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Repeated intravenous doses of nizaracianine were well tolerated. PK suggests dose proportionality for\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      , AUC (area under the curve of the plasma concentration over time) and half\u2010life, and fluorescence imaging of urine was possible from 5\u2009min up until 8\u2009h after initial dose.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70459","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T04:28:58Z","timestamp":1770611338000},"page":"2085-2094","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics, safety, tolerability and fluorescence imaging of nizaracianine triflutate administered in three divided doses to healthy volunteers"],"prefix":"10.1002","volume":"92","author":[{"given":"Lisanne K. A.","family":"Neijenhuis","sequence":"first","affiliation":[{"name":"Department of Surgery Leiden University Medical Center  Leiden The Netherlands"},{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Department of Medicine, Division of Gastroenterology and Hepatology Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7712-7556","authenticated-orcid":false,"given":"Cedric M. W.","family":"Pesch","sequence":"additional","affiliation":[{"name":"Department of Surgery Leiden University Medical Center  Leiden The Netherlands"},{"name":"Centre for Human Drug Research  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John V.","family":"Frangioni","sequence":"additional","affiliation":[{"name":"Curadel Surgical Innovations, Inc.  Bonita Springs Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander L.","family":"Vahrmeijer","sequence":"additional","affiliation":[{"name":"Department of Surgery Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacobus","family":"Burggraaf","sequence":"additional","affiliation":[{"name":"Department of Surgery Leiden University Medical Center  Leiden The Netherlands"},{"name":"Centre for Human Drug Research  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi B.","family":"Klarenbeek","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100030\u20101254297"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00464\u2010014\u20103814\u20101"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOU.0000000000000175"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiographics.22.5.g02se081005"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2013.123"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201012\u20103598"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1998.tb08185.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11014-1"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.5173\/ceju.2021.0177"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13226783"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.7363"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/1553350619827152"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/codi.15407"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.02.3187"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1089\/lap.2016.0264"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1117\/1.JBO.24.6.066004"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmig.2020.06.022"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201019\u20104156"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70459","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bcp.70459","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70459","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:33:49Z","timestamp":1784097229000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,8]]},"references-count":18,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/bcp.70459"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70459","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,8]]}}}