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.

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.

Aim: To compare the inhibitory effects of over‐the‐counter doses of famotidine or ranitidine on nocturnal intragastric acidity in a placebo‐controlled study. 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. 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. 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.

OCM is an extremely effective H. pylori eradication regimen. The 3-day regimens tested both have poor cure rates. Pre-treatment with a proton pump inhibitor, higher doses or more frequent dosing may be necessary to increase the cure rate of short duration regimens. However, this could make them less acceptable than the H. pylori eradication regimens currently available.

Inhibition of gastric acidity over the 12 h post-dose period was significantly greater and endured longer after famotidine 10 mg than after effervescent cimetidine 200 mg, but for the 60 min period immediately after dosing the effect on intragastric pH was significant following effervescent cimetidine 200 mg but not famotidine 10 mg. This suggests effervescent formulations of H2-receptor antagonists with an acid buffer have a more rapid effect on intragastric pH than film-coated tablets.