Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 177, Issue 4, Pages 769-777Publisher
WILEY
DOI: 10.1111/bph.14641
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Funding
- Hungarian National Research, Development and Innovation Office [KH17_126766, K 129286]
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Background and Purpose ATB-346 is a hydrogen sulfide (H2S)-releasing anti-inflammatory and analgesic drug. Animal studies demonstrated negligible gastrointestinal (GI) damage despite marked inhibition of COX activity and significant analgesic and anti-inflammatory effects. In humans, ATB-346 (250 mg once daily) was found to inhibit COX to the same extent as naproxen (550 mg twice daily). Experimental Approach Two hundred forty-four healthy volunteers completed a 2-week, double-blind study, taking either ATB-346 (250 mg once daily) or naproxen (550 mg twice daily), with upper GI ulceration being examined endoscopically. Key Results Forty-two per cent of the subjects taking naproxen developed at least one ulcer (>= 3-mm diameter), while only 3% of the subjects taking ATB-346 developed at least one ulcer. The two drugs produced comparable and substantial (>94%) suppression of COX activity. Subjects in the naproxen group developed more ulcers per subject than ATB-346-treated subjects and a greater incidence of larger ulcers (>= 5-mm diameter). The incidence of dyspepsia, abdominal pain, gastro-oesophageal reflux, and nausea was lower with ATB-346 than with naproxen. Subjects treated with ATB-346 had significantly higher plasma levels of H2S than those treated with naproxen. Conclusions and Implications This Phase 2B study provides unequivocal evidence for a marked reduction of GI toxicity of the H2S-releasing analgesic/anti-inflammatory drug, ATB-346, as compared to the conventional dose of naproxen that produced equivalent suppression of COX. Linked Articles This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc
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