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

Abstract

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.

Synergy between low‐dose ranitidine and antacid in decreasing gastric and oesophageal acidity and relieving meal‐induced heartburn

“…The onset of action of a low dose of ranitidine on gastric acidity observed in the present study agrees with a number of other reports. An over‐the‐counter dose of a histamine H 2 ‐receptor antagonist first reduced gastric acid concentration 1–2 h after dosing and this reduction persisted for several hours 15 , 28–31 , 35 …”

Impact of food intake on the antisecretory effect of low‐dose ranitidine and famotidine

“…Earlier studies have, however, demonstrated that at over‐the‐counter doses, cimetidine has a slightly lower antisecretory efficacy than famotidine and ranitidine 9 , . 11 On the other hand, a new effervescent preparation of 200 mg cimetidine has been shown to induce a more rapid suppressive effect on intragastric acidity than film‐coated tablets of famotidine 31 . This is likely to induce a more rapid symptom relief during the daytime.…”

“…Studies comparing the efficacy of the H 2 ‐antagonists at over‐the‐counter dosage were usually performed either in fasting or postprandial subjects 6 –11 . It is well known that meal intake reduces the acid inhibitory effect of high dose H 2 ‐antagonists 12 –14 .…”

Guidance on the use of over-the-counter proton pump inhibitors for the treatment of GERD

“…PPIs show stronger and longer acid suppression than H 2 -RAs [31][32][33][34][35]. Acid suppression lasts up to 24 h with PPIs versus 3 and 15 h with antacids and H 2 -RAs, respectively [36][37][38]. PPIs have an early onset of action (acid suppression approximately 1.5 h after administration; comparable with H 2 -RAs) that manifests clinically within 1-3 days [31,[39][40][41][42][43][44][45].…”