Gastroenterology

Gastroenterology

Volume 115, Issue 6, December 1998, Pages 1335-1339
Gastroenterology

Alimentary Tract
Ranitidine controls nocturnal gastric acid breakthrough on omeprazole: A controlled study in normal subjects☆,☆☆

Presented at the Annual Scientific Meeting of the American College of Gastroenterology, Chicago, Illinois, November 1997.
https://doi.org/10.1016/S0016-5085(98)70010-1Get rights and content

Abstract

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.

GASTROENTEROLOGY 1998;115:1335-1339

Section snippets

Subjects

Twelve healthy, asymptomatic volunteers, with a mean age of 31 years (range, 21–40 years; 7 men and 5 women; ethnic distribution: white, 9; black, 2; Asian, 1) were studied. All had negative serological results for immunoglobulin (Ig) G antibodies to Helicobacter pylori (FlexSure HP; SmithKline Diagnostics, Inc., San Jose, CA).

Study design

Subjects were pretreated with oral omeprazole, 20 mg twice daily 15–30 minutes before breakfast and dinner, for 7 days. Beginning on day 8, additional treatments with

Results

Median intragastric pH values for the 8-hour overnight period were 4.2 (IQR, 2.9–5.0) for omeprazole twice daily with placebo at bedtime; 5.7 (IQR, 5.0–6.4) for the regimen with three doses of omeprazole (P < 0.005 vs. placebo); and 7.2 (IQR, 6.3–7.4) and 7.2 (IQR, 6.9–7.4) for 150 mg and 300 mg ranitidine, respectively, in addition to omeprazole twice daily (P < 0.001 vs. placebo and vs. additional omeprazole; Figure 1).

. Median intragastric (IG) pH values with 4 treatments in 12 subjects. The

Discussion

This study confirms our previous findings of a high prevalence of nocturnal acid breakthrough in patients being treated with proton pump inhibitor twice daily.1 Acid breakthrough, defined as a decrease in intragastric pH to <4 for 1 hour or more, occurred in more than 90% of the volunteers. Although this observation appears to be in conflict with general knowledge regarding acid suppression by omeprazole, the discrepancy is explained by differences in the way the acid-inhibiting effect of

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Address requests for reprints to: Donald O. Castell, M.D., Department of Medicine, Suite 501, Pepper Pavilion, Allegheny University Hospitals, Graduate, One Graduate Plaza, 1800 Lombard Street, Philadelphia, Pennsylvania 19146. Fax: (215) 893-2472.

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Supported by grants from the American College of Gastroenterology Institute of Research, from Glaxo Welcome, Inc., and from the Theodor and Ida Herzog-Egli Foundation, Zürich, Switzerland.

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