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Notes: Background: There are no published comparative studies on the effect of low-dose H2-antagonists on pentagastrin-stimulated gastric acid secretion. Methods: Twenty-four healthy subjects were dosed with either famotidine 10 mg, ranitidine 75 mg or placebo in a balanced three-period cross-over design. The subjects were studied in groups of 12, simultaneously, under identical controlled environmental conditions. Gastric juice was aspirated in 15-min aliquots during sub-maximal (0.6 μg . h/kg) intravenous pentagastrin stimulation in the third and fourth hours (early period) and the eighth and ninth hours (late period) after oral dosing. The hydrogen ion (H+) content of gastric juice was measured ex vivo, by titrating to pH 7 known volumes of gastric aspirate against 0.1 m sodium hydroxide, using a versatile microprocessor-controlled auto-titration unit. Gastric acid output during the period of interest was calculated by adding the hydrogen ion content of 15-min aliquots collected during that period. The geometric mean of the cumulative pentagastrin-stimulated gastric acid output during the early and late periods was determined for the subjects dosed with either famotidine, ranitidine or placebo. Comparisons were performed by ANOVA. Results: During the early period (2–4 h post-dose), when the subjects were given placebo, mean gastric acid output was 46.6 mmol, decreasing by 76% to 11.3 mmol (P〈0.001) when treated with famotidine and by 76% to 11.1 mmol (P〈0.001) when treated with ranitidine. During the late period (7–9 h post-dose), when the subjects were dosed with placebo, mean gastric acid output was 41.2 mmol, decreasing by 38% to 25.7 mmol (P〈0.001) when treated with famotidine and by 27% to 30.0 mmol (P=0.007) when treated with ranitidine. The difference between the inhibitory effects of famotidine and ranitidine on gastric acid output were non-significant during either period. Conclusions: Low-dose famotidine and ranitidine, intended for over-the-counter use, inhibit stimulated gastric acid secretion profoundly in the third and fourth hours after an oral dose. Modest effects are still detectable up to 9 h after dosing.

Notes: 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.〈section xml:id="abs1-2"〉〈title type="main"〉MethodsProfiles 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.〈section xml:id="abs1-3"〉〈title type="main"〉ResultsThe 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.〈section xml:id="abs1-4"〉〈title type="main"〉ConclusionsIn 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.

Notes: To compare the inhibitory effects of over-the-counter doses of famotidine or ranitidine on nocturnal intragastric acidity in a placebo-controlled study.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:Twelve-hour intragastric acidity was measured simultaneously in 24 healthy subjects who ate a standard meal at 18.30 h and were dosed (at 19.30 h) with either famotidine 10 mg, ranitidine 75 mg or placebo in a balanced three-period crossover design. Five-millilitre aliquots of gastric juice were aspirated half-hourly 0–3 h post-dose, and then hourly until the end of the study. pH was measured with a glass electrode. Integrated pH (area under the curve (AUC) of the pH–time curve) was calculated for the intervals 0–12 h and 9–12 h post-dose. Statistical analysis was by ANOVA.〈section xml:id="abs1-3"〉〈title type="main"〉Results:In the 0–12 h post-dose period, when the 24 subjects were dosed with placebo, mean AUC was 2.12, dosed increasing by 75% to 3.70 with famotidine (P 〈 0.001) and by 81% to 3.83 with ranitidine (P 〈 0.001). In the 9–12 h post-dose period, when the subjects were dosed with placebo, mean AUC was 2.13 increasing by 91% to 4.07 with famotidine (P 〈 0.001) and by 79% to 3.82 with ranitidine (P 〈 0.001). There was no significant difference between the pH-raising effects of famotidine and ranitidine in both periods.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:Famotidine and ranitidine in over-the-counter doses have a similar, sustained, effect on post-prandial nocturnal intragastric acidity in healthy subjects lasting up to 12 h after oral dosing.