{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:14:52Z","timestamp":1788243292938,"version":"build-2803163510"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      SPH3127 (Sitokiren), a novel direct renin inhibitor used to treat hypertension, is currently approved for marketing in China. The primary objective of this study was to determine the pharmacokinetics, mass balance, and biotransformation of [\n                      <jats:sup>14<\/jats:sup>\n                      C]SPH3127 in humans after the drug was administered to healthy Chinese male subjects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The absorption, metabolism, and excretion of SPH3127 were characterised via isotope labeling technology in six healthy Chinese male subjects after receiving a single 100\u00a0mg oral dose of [\n                      <jats:sup>14<\/jats:sup>\n                      C]SPH3127 (100\u00a0\u03bcCi).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SPH3127 was rapidly absorbed, with median T\n                      <jats:sub>max<\/jats:sub>\n                      values of 0.417 and 0.75\u00a0h observed for the parent drug and total radioactivity in human plasma. The arithmetic mean plasma half-life (t\n                      <jats:sub>1\/2<\/jats:sub>\n                      ) was approximately 4.83\u00a0h for SPH3127-related material. After 192\u00a0h of dosing, the mean cumulative excreted radioactivity was 101.66% of the dose, with 44.35% in urine and 57.31% in feces, indicating that urinary and fecal excretions were comparable and served as the primary elimination routes. Metabolite profiling revealed that the parent drug was detected in plasma, as well as in feces and urine. Twelve major metabolites in plasma, urine, and feces were analysed and identified. The principal metabolic pathways involved oxidation, dehydrogenation, hydrolysis, glucuronidation, and sulfation. SPH3127 was found to be safe, with no serious adverse events reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SPH3127 showed favourable pharmacokinetic characteristics and safety profiles in this study. SPH3127 was rapidly absorbed and extensively metabolized in humans. The main excretion route of SPH3127 and its metabolites was through urine and feces.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>http:\/\/www.chinadrugtrials.org.cn\/<\/jats:ext-link>\n                      , identifier CTR20222187.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1893643","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:33:39Z","timestamp":1788240819000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics, mass balance, and metabolism of [14C]SPH3127 (sitokiren), a novel direct renin inhibitor in humans"],"prefix":"10.3389","volume":"17","author":[{"given":"Sheng","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Pharmacy, the First Affiliated Hospital of Soochow University","place":["Suzhou, China"]},{"name":"Institute for Interdisciplinary Drug Research and Translational Sciences, Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xintong","family":"Huang","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]},{"name":"University of Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Yan","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haonan","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, the First Affiliated Hospital of Soochow University","place":["Suzhou, China"]},{"name":"Institute for Interdisciplinary Drug Research and Translational Sciences, Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Cui","sequence":"additional","affiliation":[{"name":"Shanghai Pharmaceuticals Holding Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cungang","family":"Ding","sequence":"additional","affiliation":[{"name":"Shanghai Pharmaceuticals Holding Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"Diao","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]},{"name":"University of Chinese Academy of Sciences","place":["Beijing, China"]},{"name":"Tianjin University of Traditional Chinese Medicine","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, the First Affiliated Hospital of Soochow University","place":["Suzhou, China"]},{"name":"Institute for Interdisciplinary Drug Research and Translational Sciences, Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2492","DOI":"10.1161\/01.CIR.0000131449.94713.AD","article-title":"Combined blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists","volume":"109","author":"Azizi","year":"2004","journal-title":"Circulation"},{"key":"B2","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1111\/bcp.14363","article-title":"Mass balance, pharmacokinetics and pharmacodynamics of intravenous HSK3486, a novel anaesthetic, administered to healthy subjects","volume":"87","author":"Bian","year":"2021","journal-title":"Br. 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