{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:26:37Z","timestamp":1792715197071,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T00:00:00Z","timestamp":1554940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>ATB\u2010346 is a hydrogen sulfide (H<jats:sub>2<\/jats:sub>S)\u2010releasing anti\u2010inflammatory and analgesic drug. Animal studies demonstrated negligible gastrointestinal (GI) damage despite marked inhibition of COX activity and significant analgesic and anti\u2010inflammatory effects. In humans, ATB\u2010346 (250\u00a0mg once daily) was found to inhibit COX to the same extent as naproxen (550\u00a0mg twice daily).<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Two hundred forty\u2010four healthy volunteers completed a 2\u2010week, double\u2010blind study, taking either ATB\u2010346 (250\u00a0mg once daily) or naproxen (550\u00a0mg twice daily), with upper GI ulceration being examined endoscopically.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Forty\u2010two per cent of the subjects taking naproxen developed at least one ulcer (\u22653\u2010mm diameter), while only 3% of the subjects taking ATB\u2010346 developed at least one ulcer. The two drugs produced comparable and substantial (&gt;94%) suppression of COX activity. Subjects in the naproxen group developed more ulcers per subject than ATB\u2010346\u2010treated subjects and a greater incidence of larger ulcers (\u22655\u2010mm diameter). The incidence of dyspepsia, abdominal pain, gastro\u2010oesophageal reflux, and nausea was lower with ATB\u2010346 than with naproxen. Subjects treated with ATB\u2010346 had significantly higher plasma levels of H<jats:sub>2<\/jats:sub>S than those treated with naproxen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>This Phase 2B study provides unequivocal evidence for a marked reduction of GI toxicity of the H<jats:sub>2<\/jats:sub>S\u2010releasing analgesic\/anti\u2010inflammatory drug, ATB\u2010346, as compared to the conventional dose of naproxen that produced equivalent suppression of COX.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Hydrogen Sulfide in Biology &amp; Medicine. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v177.4\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v177.4\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14641","type":"journal-article","created":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T03:13:29Z","timestamp":1551755609000},"page":"769-777","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":106,"title":["A proof\u2010of\u2010concept, Phase 2 clinical trial of the gastrointestinal safety of a hydrogen sulfide\u2010releasing anti\u2010inflammatory drug"],"prefix":"10.1111","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4853-1682","authenticated-orcid":false,"given":"John L.","family":"Wallace","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology University of Calgary  Calgary AB Canada"},{"name":"Antibe Therapeutics Inc.  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