Persistent acid secretion during omeprazole therapy: a study of gastric acid profiles in patients demonstrating failure of omeprazole therapy

Am J Gastroenterol. 1996 Aug;91(8):1527-31.


Objective: To identify patients with gastroesophageal reflux disease (GERD) who, despite omeprazole 20 mg b.i.d., demonstrate continued abnormal gastric acid secretion.

Methods: Eighty-eight patients with GERD completed ambulatory gastric and esophageal pH monitoring for persistent symptoms on omeprazole 20 mg b.i.d.. Seventeen (19%) demonstrated abnormal gastric acid secretion (percentage time gastric pH < 4 > 50%). The 17 omeprazole failures (OF) were compared with: 1) 19 randomly selected patients with GERD (also studied on omeprazole 20 mg b.i.d. and 2) 19 normal volunteers studied on both placebo and omeprazole 20 mg b.i.d.. Total time intragastric pH < 4, 24-hr gastric pH frequency distribution, and 15-min median pH values for the 6-h period after the evening omeprazole dose were compared.

Results: Both the 24-hr frequency distribution for gastric pH and the 15-min median gastric pH profile for patients with GERD and volunteers on omeprazole 20 mg b.i.d. were almost identical. By contrast, gastric pH studies from the OF group receiving omeprazole 20 mg b.i.d. most closely resembled those of the normal subjects receiving placebo, with respect to these variables. Gastric pH monitoring in seven of the 17 OF patients while on omeprazole 80 mg/day demonstrated a significant decrease in the median percentage time gastric pH remained below 4 (32.8% on 80 mg/day vs 74.3% on 40 mg/day; p < 0.02).

Conclusion: There are individuals whose intragastric acidity persists despite conventional doses of omeprazole. Although the underlying mechanism remains unclear, the majority (six of seven) (87%) demonstrated improved gastric acid control when placed on high dose omeprazole, indicating that this is often a dose-dependent phenomenon.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Ulcer Agents / administration & dosage
  • Anti-Ulcer Agents / therapeutic use*
  • Case-Control Studies
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Gastric Acid / metabolism*
  • Gastric Acidity Determination
  • Gastroesophageal Reflux / drug therapy*
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Middle Aged
  • Monitoring, Ambulatory
  • Omeprazole / administration & dosage
  • Omeprazole / therapeutic use*
  • Random Allocation
  • Time Factors
  • Treatment Failure


  • Anti-Ulcer Agents
  • Omeprazole