{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:29:17Z","timestamp":1784939357636,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Paltusotine is a novel, nonpeptide, selective somatostatin receptor 2 agonist in development for the treatment of acromegaly and carcinoid syndrome. This study investigated the mass balance, routes of excretion, absolute bioavailability and metabolite profile of orally administered paltusotine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In Part A of the two\u2010part, phase 1 study, a single dose (oral solution) of 20\u2009mg paltusotine containing approximately 3.0\u00a0MBq (80\u2009\u03bcCi) of\n                      <jats:sup>14<\/jats:sup>\n                      C\u2010labelled paltusotine was administered to six healthy male participants to evaluate the mass balance and metabolite profile of paltusotine. In Part B, a single dose (oral solution) of paltusotine 20\u2009mg followed approximately 90\u2009min later by a single microtracer intravenous bolus injection of approximately 50\u2009\u03bcg paltusotine containing 0.0185\u2009MBq (0.5\u00a0\u03bcCi) of\n                      <jats:sup>14<\/jats:sup>\n                      C\u2010labelled paltusotine was administered to five healthy male participants to assess absolute bioavailability of paltusotine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The mean absolute bioavailability of paltusotine 20\u2009mg was 69% (90% CI 59\u201382%). The mean recovery of total radioactivity was 94% (90% in faeces and 3.9% in urine), with excretion primarily via the biliary route. The exposure (AUC\n                      <jats:sub>0\u2010inf<\/jats:sub>\n                      ) ratio of unchanged paltusotine to total reactivity in plasma was 0.75, indicating that there were no abundant circulating metabolites. The geometric mean half\u2010life (\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>1\/2<\/jats:sub>\n                      ) for paltusotine in plasma was 26\u201328\u2009h. Treatment\u2010emergent adverse events associated with paltusotine were mild and transient.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Oral dosing with paltusotine is associated with efficient absorption from the gastrointestinal tract. Most of the administered dose is excreted unchanged. Pharmacokinetic properties of paltusotine are supportive of once\u2010daily dosing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70020","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T16:27:11Z","timestamp":1741364831000},"page":"2070-2079","source":"Crossref","is-referenced-by-count":9,"title":["Oral paltusotine, a nonpeptide selective somatostatin receptor 2 agonist: Mass balance, absolute bioavailability and metabolism in healthy participants"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8003-2271","authenticated-orcid":false,"given":"Rosa","family":"Luo","sequence":"first","affiliation":[{"name":"Crinetics Pharmaceuticals  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Madan","sequence":"additional","affiliation":[{"name":"Crinetics Pharmaceuticals  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine T.","family":"Ferrara\u2010Cook","sequence":"additional","affiliation":[{"name":"Crinetics Pharmaceuticals  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Dalvie","sequence":"additional","affiliation":[{"name":"Crinetics Pharmaceuticals  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance","family":"Goulet","sequence":"additional","affiliation":[{"name":"Crinetics Pharmaceuticals  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Scott","family":"Struthers","sequence":"additional","affiliation":[{"name":"Crinetics Pharmaceuticals  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S.","family":"Krasner","sequence":"additional","affiliation":[{"name":"Crinetics Pharmaceuticals  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010019\u20100071\u20106"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018\u201000115"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2021.1908998"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154\u2010020\u201009588\u2010z"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2013.07.005"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab726"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20123049"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC\u201018\u20100495"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12902\u2010020\u201000595\u20104"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE\u201015\u20101042"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e318279d552"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008\u20100019"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac385"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.2c00431"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102\u2010021\u201001201\u2010z"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac643"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae385"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvae163.1201"},{"key":"e_1_2_10_20_1","volume-title":"European Neuroendocrine Tumor Society; March 13\u201015, 2024; Vienna, Austria","author":"Chauhan A"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13403"},{"key":"e_1_2_10_22_1","volume-title":"Clinical pharmacology considerations for human radiolabeled mass balance studies: guidance for industry","author":"US Department of Health and Human Services, US Food and Drug Administration, Center for Drug Evaluation and Research","year":"2022"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12466"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/js970486q"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14748"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425247.2021.1942838"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012\u20101179"},{"key":"e_1_2_10_28_1","volume-title":"Mycapssa clinical pharmacology review","author":"Office of Clinical Pharmacology, Center for Drug Evaluation and Research (CDER)","year":"2019"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvab048"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T03:49:30Z","timestamp":1764560970000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,5]]},"references-count":28,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/bcp.70020"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70020","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,5]]}}}