{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:40:09Z","timestamp":1784544009878,"version":"3.55.0"},"reference-count":27,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Fosun Pharmaceutical Development, Co., Ltd"},{"name":"Wanbang Biopharmaceuticals"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["International Journal of Clinical Practice"],"published-print":{"date-parts":[[2024,3,6]]},"abstract":"<jats:p>Background. Tenapanor is a locally acting selective sodium-hydrogen exchanger 3 inhibitor with the potential to treat sodium\/phosphorus and fluid overload in various cardiac-renal diseases, which has been approved for constipation-predominant irritable bowel syndrome in the US. The pharmacokinetics (PK) of tenapanor and its metabolite tenapanor-M1 (AZ13792925), as well as the safety and tolerability of tenapanor, were investigated in healthy Chinese and Caucasian subjects. Methods. This randomized, open-label, single-center, placebo-controlled phase 1 study (https:\/\/www.chinadrugtrials.org.cn; CTR20201783) enrolled Chinese and Caucasian healthy volunteers into 4 parallel cohorts (3 cohorts for Chinese subjects, 1 cohort for Caucasian subjects). In each cohort, 15 subjects were expected to be included and received oral tenapanor (10 or 30\u2009mg as single dose, or 50\u2009mg as a single dose followed by a twice-daily repeated dose from Day 5 to 11, with a single dose in the morning on Day 11) or placebo in a 4\u2009:\u20091 ratio. Results. 59 healthy volunteers received tenapanor 10\u2009mg (n\u2009=\u200912 Chinese), 30\u2009mg (n\u2009=\u200912 Chinese), or 50\u2009mg (n\u2009=\u200912 (Chinese), n\u2009=\u200911 (Caucasian)) or placebo (n\u2009=\u200912, 3 per cohort). After single and twice-daily repeated doses, tenapanor plasma concentrations were all below the limit of quantitation; tenapanor-M1 appeared slowly in plasma. In single-ascending dose evaluation (10 to 50\u2009mg) of Chinese subjects, the mean <jats:inline-formula><a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><a:msub><a:mrow><a:mi>C<\/a:mi><\/a:mrow><a:mrow><a:mi mathvariant=\"normal\">max<\/a:mi><\/a:mrow><\/a:msub><\/a:math><\/jats:inline-formula>, AUC0-t, and AUC0-\u221e of tenapanor-M1 increased with increasing dose level, and AUC0-t increased approximately dose proportionally. The <jats:inline-formula><d:math xmlns:d=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><d:msub><d:mrow><d:mi>C<\/d:mi><\/d:mrow><d:mrow><d:mi mathvariant=\"normal\">max<\/d:mi><\/d:mrow><\/d:msub><\/d:math><\/jats:inline-formula> accumulation ratio was 1.55 to 6.92 after 50\u2009mg repeated dose in Chinese and Caucasian subjects. Exposure to tenapanor-M1 was generally similar between the Chinese and Caucasian subjects. Tenapanor was generally well-tolerated and the safety profile was similar between the Chinese and Caucasian participants receiving tenapanor 50\u2009mg, as measured by vital signs, physical and laboratory examination, 12-lead ECG, and adverse events. No serious adverse event or adverse event leading to withdrawal occurred. Conclusion. Tenapanor was well-tolerated, with similar PK and safety profiles between Chinese and Caucasian subjects. This trial is registered with CTR20201783.<\/jats:p>","DOI":"10.1155\/2024\/1386980","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T18:20:08Z","timestamp":1709749208000},"page":"1-10","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetics, Safety, and Tolerability of Tenapanor in Healthy Chinese and Caucasian Volunteers: A Randomized, Open-Label, Single-Center, Placebo-Controlled Phase 1 Study"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7715-8787","authenticated-orcid":true,"given":"Gang","family":"Yuan","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8455-9378","authenticated-orcid":true,"given":"Yili","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Sun Yat-sen 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2998-1645","authenticated-orcid":true,"given":"Jiawei","family":"Zeng","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3688-1570","authenticated-orcid":true,"given":"Ai-Min","family":"Hui","sequence":"additional","affiliation":[{"name":"Global R&D Center, Shanghai Fosun Pharmaceutical Development, Co., Ltd, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4394-683X","authenticated-orcid":true,"given":"Yueyun","family":"Jiang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 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