Predictable prolonged suppression of gastric acidity with a novel proton pump inhibitor, AGN 201904-Z.
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.


OBJECTIVE
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.
Hunt
R H
RH
Division of Gastroenterology, McMaster University and Hamilton Health Science Centre, Hamilton, ON, Canada. huntr@mcmaster.ca
Armstrong
D
D
Yaghoobi
M
M
James
C
C
Chen
Y
Y
Leonard
J
J
Shin
J M
JM
Lee
E
E
Tang-Liu
D
D
Sachs
G
G
D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D064098:Esomeprazole; D005745:Gastric Acidity Determination; D005764:Gastroesophageal Reflux / Q000517:prevention & control*; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D016896:Treatment Outcome
C532272:AGN 201904; D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D009853:Omeprazole; D064098:Esomeprazole