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Predictable prolonged suppression of gastric acidity with a novel proton pump inhibitor, AGN 201904‐Z
Author(s) -
HUNT R. H.,
ARMSTRONG D.,
YAGHOOBI M.,
JAMES C.,
CHEN Y.,
LEONARD J.,
SHIN J. M.,
LEE E.,
TANGLIU D.,
SACHS G.
Publication year - 2008
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2008.03725.x
Subject(s) - esomeprazole , omeprazole , proton pump inhibitor , medicine , nocturnal , gastric acid , pharmacokinetics , gastroenterology , pharmacology , pharmacodynamics , stomach
Summary Background AGN 201904‐Z is a new, slowly absorbed, acid‐stable pro‐proton pump inhibitor (pro‐PPI) rapidly converted to omeprazole in the systemic circulation giving a prolonged residence time. Aim To investigate pharmacodynamics and pharmacokinetics of AGN 201904‐Z compared to esomeprazole. Methods A randomized, open‐label, parallel group, investigator‐blinded intragastric pH study was conducted in 24 healthy Helicobacter pylori negative male volunteers. AGN 201904‐Z enteric‐coated capsules (600 mg/day) or esomeprazole delayed‐release tablets (40 mg/day) were administered for 5 days. Twenty‐four‐hour intragastric pH recordings were acquired at baseline, days 1, 3 and 5 with blood levels of omeprazole, AGN 201904‐Z and gastrin. Results On day 1, median nocturnal pH and proportion of nocturnal time with pH ≥4 and 24‐h and nocturnal time pH ≥5 were significantly higher with AGN 201904‐Z than esomeprazole. At day 5, 24‐h and median nocturnal pH were significantly higher for AGN 201904‐Z than esomeprazole ( P < 0.0001). There was also a marked reduction in periods of nocturnal pH <4.0. Area under curve of the AGN 201904‐Z active metabolite (omeprazole) in the blood was twice that of esomeprazole at day 5. Conclusions AGN 201904‐Z produced a significantly greater and more prolonged acid suppression than esomeprazole, and nocturnal acid suppression was more prolonged over all 5 days. AGN 201904‐Z should provide true once‐a‐day treatment and better clinical efficacy than current PPIs.