Royal Free Hospital Protocol for 24-Hour Intragastric Acidity and Plasma Gastrin Concentration

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Background: Histamine H2‐receptor antagonists are available over the counter for the treatment of heartburn. Aim: To compare the effects of low doses of ranitidine and famotidine on intragastric acidity in a three‐way crossover study. Methods: Healthy subjects (12 male, 12 female) were dosed on three occasions with single oral doses of placebo, ranitidine, 75 mg, and famotidine, 10 mg, 1 h after lunch. The pH of gastric aspirates was then measured for 20 h. Subjects ate standard meals and snacks. Analysis of variance was used to determine the statistical significance of differences in acidity (mmol/L) during the day (12.30–22.30 hours) and night (22.30–08.30 hours). Results: Ranitidine and famotidine were superior (P < 0.05) to placebo in decreasing acidity for daytime and night‐time intervals. There were no significant differences in mean gastric acidity between ranitidine and famotidine during the daytime (11.37 mmol/L vs. 13.42 mmol/L, respectively) and night‐time (23.57 mmol/L vs. 24.74 mmol/L, respectively). Intragastric acidity after ranitidine was significantly lower than that after famotidine in the first 2.5‐h period following dosing (4.32 mmol/L vs. 9.28 mmol/L; P < 0.05). Conclusions: Lunchtime doses of ranitidine and famotidine decreased acidity during day‐ and night‐time periods. The effect of ranitidine was significantly greater for the first 2.5 h after dosing.

Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

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Control of intragastric acidity with over‐the‐counter doses of ranitidine or famotidine

Hamilton

Sercombe

Pounder

2001

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“…Subjects were evaluated (medical history, physical examination and laboratory tests) at a pre‐study screening visit to confirm eligibility and were asked to return on five separate occasions to undergo intragastric pH measurements using a modified form of the Royal Free protocol for measuring intragastric acidity 10 …”

Section: Methodsmentioning

confidence: 99%

The effects of low doses of ranitidine on intragastric acidity in healthy men

Wyeth

Pounder

Sercombe

et al. 1998

Background: H2‐receptor antagonists are becoming widely available as over‐the‐counter medications for the treatment of heartburn and excess gastric acidity. Aim: To determine the effects of single low doses of ranitidine on intragastric acidity. Methods: Intragastric pH was measured for 9 h after lunch in five studies involving 24 healthy male volunteers. Antacid was given to all subjects on day 1. They then received single oral doses of a study drug 45 min after lunch on four separate occasions: placebo and either ranitidine 25 mg, 75 mg or 125 mg were given double‐blind according to a predetermined randomization schedule. Results: During both of the post‐dosing time periods (0–5 h and 5–9 h) there were significant decreases in integrated intragastric acidity for each ranitidine dose compared with placebo (P < 0.0001). There was a significant linear relationship between dose and integrated intragastric acidity with a greater decrease in acidity with increasing ranitidine doses (P < 0.0001). Compared with placebo, time with pH > 3 was significantly greater for ranitidine 75 mg and 125 mg (P < 0.001), but not ranitidine 25 mg. Results with the antacid were similar to placebo. Conclusions: Using low doses of ranitidine (25, 75 or 125 mg) there was a dose‐related decrease in intragastric acidity for 9 h after dosing. A single dose of antacid did not decrease intragastric acidity significantly.

“…9 They were assigned to one of six dosing sequences as determined by two three-period Latin squares. There was a washout period of at least 6 days between each study.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of intragastric acidity in healthy subjects dosed with ranitidine 75 mg: a comparative study with cimetidine and placebo

Grimley

Constantinides

Snell

et al. 1997

Background Despite the widespread use of over‐the‐counter H2‐receptor antagonists little is known about their duration of action on human gastric acid secretion. There are studies reporting inhibitory effects for up to 9 h post‐dose but few data beyond this period. Methods Profiles of 20‐h intragastric acidity were measured simultaneously in 24 healthy subjects who were dosed (at 12.30 h) with either ranitidine 75 mg, cimetidine 200 mg or placebo in a three‐way crossover study, according to a standard protocol. Five‐millilitre aliquots of gastric juice were aspirated half‐hourly during the day (0–10 h post‐dose) and hourly overnight (10–20 h post‐dose). pH was measured to three decimal places with a glass electrode. Weighted intragastric acidity (AUC/time) was calculated for both day‐ and night‐times using 2.5‐h intervals during the day and 5‐h intervals at night. Statistical analysis was by ANOVA. Results The results are expressed as mean weighted intragastric acidity (mmol/L). (i) Daytime (0–10 h post‐dose): when dosed with placebo the weighted intragastric acidity was 31.03, decreasing to 10.37 (P < 0.001 vs. placebo) and 16.23 (P < 0.001 vs. placebo) when treated with ranitidine and cimetidine, respectively. Ranitidine inhibited weighted intragastric acidity to a greater degree than cimetidine (P < 0.001) during this period. (ii) Night‐time (10–20 h post‐dose): when dosed with placebo the weighted intragastric acidity was 21.36 decreasing to 16.65 (P < 0.001 vs. placebo) when dosed with ranitidine and remaining unchanged at 20.03 (P = 0.886 vs. placebo) when dosed with cimetidine. Ranitidine inhibited weighted intragastric acidity to a greater degree than cimetidine (P = 0.010) during this period. A sub‐analysis of the two 5‐h intervals showed that compared to placebo, ranitidine inhibited weighted intragastric acidity significantly in the 10–15 h period. However, its effect in the 15–20 h period did not differ from placebo. Conclusions In healthy subjects, the inhibitory effect of ranitidine 75 mg on intragastric acidity can be detected 10–15 h after an oral dose. By contrast, the inhibitory effect of cimetidine 200 mg seems to be restricted to the first 10 h.