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 >or=4 and 24-h and nocturnal time pH >or=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.
RCT Entities:
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 >or=4 and 24-h and nocturnal time pH >or=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.
Authors: L Lundell; P Miettinen; H E Myrvold; S A Pedersen; B Liedman; J G Hatlebakk; R Julkonen; K Levander; J Carlsson; M Lamm; I Wiklund Journal: J Am Coll Surg Date: 2001-02 Impact factor: 6.113
Authors: Donald O Castell; Peter J Kahrilas; Joel E Richter; Nimish B Vakil; David A Johnson; Seth Zuckerman; Wendy Skammer; Jeffrey G Levine Journal: Am J Gastroenterol Date: 2002-03 Impact factor: 10.864
Authors: J E Richter; P J Kahrilas; J Johanson; P Maton; J R Breiter; C Hwang; V Marino; B Hamelin; J G Levine Journal: Am J Gastroenterol Date: 2001-03 Impact factor: 10.864