{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:01:22Z","timestamp":1773010882493,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":197,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advances in Pharmacological and Pharmaceutical Sciences"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    NorUrsodeoxycholic acid (norUDCA) is a side\u2010chain\u2010shortened derivative of ursodeoxycholic acid (UDCA) with specific pharmacological properties, including cholehepatic shunting, making it a promising candidate for a range of cholestatic and metabolic liver diseases. This phase I study evaluates the safety, tolerability, and pharmacokinetics of single ascending doses of norUDCA in healthy adults under fasting conditions. In this open\u2010label, dose\u2010escalation study, healthy adults (aged 18\u201345\u2009years) were enrolled into 3 successive dose escalation cohorts, receiving norUDCA oral tablets of 500\u2009mg (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200914), 1000\u2009mg (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200914), and 1500\u2009mg (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200914) once daily. The primary endpoints were the incidence rate of dose\u2010limiting toxicities (DLTs), assessment of maximum tolerated dose (MTD) after single dose administration, and an establishment of the recommended phase II dose. Secondary endpoints included pharmacokinetic assessments and evaluation of dose proportionality. Following single\u2010dose administration of 500\u2009mg, 1000\u2009mg, and 1500\u2009mg, no DLTs were observed, and the MTD was determined to be 1500\u2009mg\/day. Maximum plasma concentration (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ) and plasma exposure [area under the curve (AUC)] to norUDCA increased dose proportionally from 500 to 1500\u2009mg\/day. Median time to achieve maximum plasma concentration (\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ) for norUDCA at 1500\u2009mg\/day cohort (3\u2009h) was comparable to 1000\u2009mg\/day cohort (3\u2009h) but lower than 500\u2009mg\/day cohort (4\u2009h). The half\u2010life was longer in 1500\u2009mg\/day (16\u2009h) cohort compared to 500\u2009mg\/day (15\u2009h) and 1000\u2009mg\/day cohorts (14\u2009h). The 90% confidence interval of the slope estimates for\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    (22.41, 59.70), AUC\n                    <jats:sub>\n                      0\u2212\n                      <jats:italic>t<\/jats:italic>\n                    <\/jats:sub>\n                    (11.71, 61.14), and AUC\n                    <jats:sub>0\u2212inf<\/jats:sub>\n                    (10.74, 61.86) did not consistently fall within the predefined acceptable limits (79.69, 120.31) for formal dose proportionality criteria. No serious adverse events or deaths occurred in any cohort. One treatment\u2010emergent adverse event was observed (an increase in the white blood cell count), which was not related to the study drug. A single dose of norUDCA is safe and well\u2010tolerated, with favorable plasma pharmacokinetic profiles in healthy subjects. Based on the safety and pharmacokinetic data, the recommended dosage for further clinical trials is 1500\u2009mg\/day.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    Clinical Trials Registry\u2010India: CTRI\/2022\/11\/047561\n                  <\/jats:p>","DOI":"10.1155\/adpp\/6613969","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T17:33:43Z","timestamp":1752773623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety, Tolerability, and Pharmacokinetics of NorUrsodeoxycholic Acid (Shilpa Medicare Limited, India) in Healthy Adults: Results From a Phase I Open\u2010Label Dose\u2010Escalation Study"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2623-5032","authenticated-orcid":false,"given":"Veerendra Kumar","family":"Panuganti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5362-1007","authenticated-orcid":false,"given":"Chandrasekhar Varma","family":"Alluri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8930-7153","authenticated-orcid":false,"given":"Mamatha Reddy","family":"Dundigalla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8983-2608","authenticated-orcid":false,"given":"Javeed","family":"Mohammad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3297-3805","authenticated-orcid":false,"given":"Pavan Kumar","family":"Madala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4125-1200","authenticated-orcid":false,"given":"Sanyasirao","family":"K. 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