Ranitidine controls nocturnal gastric acid breakthrough on omeprazole: a controlled study in normal subjects

Gastroenterology. 1998 Dec;115(6):1335-9. doi: 10.1016/s0016-5085(98)70010-1.


Background & aims: Proton pump inhibitors administered twice daily do not provide complete nocturnal acid suppression. Acid breakthrough, or decrease in intragastric pH to <4 for an hour or longer, occurs in three quarters of normal subjects and patients at night. We compared the effect of a third dose of omeprazole at bedtime with that of a dose of ranitidine at bedtime on residual nocturnal acid secretion in patients receiving omeprazole twice daily.

Methods: Twelve volunteers underwent overnight intragastric pH monitoring after 7 days of treatment with omeprazole, 20 mg twice daily, followed by different treatment supplements at bedtime: placebo; additional omeprazole, 20 mg; ranitidine, 150 mg; and ranitidine, 300 mg.

Results: Additional omeprazole at bedtime reduced the percentage of time with intragastric pH of <4 from 48% to 31% (P < 0.005) compared with omeprazole twice daily with placebo at bedtime. Ranitidine at bedtime reduced this parameter more, 5% with 150 mg and 6% with 300 mg (P <0.01 vs. omeprazole twice daily plus bedtime). Results for percentage of time with intragastric pH <3 were similar. Eleven subjects had acid breakthrough with placebo at bedtime; 7 with omeprazole at bedtime (P = NS); 4 with ranitidine, 150 mg at bedtime; and 3 with ranitidine, 300 mg at bedtime (P < 0. 05, ranitidine vs. placebo).

Conclusions: Bedtime ranitidine is more effective than bedtime omeprazole on residual nocturnal acid secretion in patients receiving omeprazole twice daily. This finding suggests that fasting breakthrough nocturnal acid secretion in patients receiving omeprazole twice daily is most likely histamine related.

Publication types

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

MeSH terms

  • Adult
  • Anti-Ulcer Agents / therapeutic use*
  • Circadian Rhythm
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Gastric Acid / metabolism*
  • Gastric Acidity Determination
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • Male
  • Omeprazole / therapeutic use*
  • Ranitidine / therapeutic use*


  • Anti-Ulcer Agents
  • Ranitidine
  • Omeprazole