INHIBITION OF INTRAGASTRIC ACIDITY IN HEALTHY-SUBJECTS DOSED WITH RANITIDINE 75 MG - A COMPARATIVE-STUDY WITH CIMETIDINE AND PLACEBO

Background: Despite the widespread use of over-the-counter H-2-recepto r 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: Pro files 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, acco rding to a standard protocol, Five-millilitre aliquots of gastric juic e were aspirated half-hourly during the day (0-10 h post-dose) and hou rly overnight (10-20 h post-dose). pH was measured to three decimal pl aces with a glass electrode. Weighted intragastric acidity (AUC/time) was calculated for both day- and night-times using 2.5-h intervals dur ing the day and 5-h intervals at night, Statistical analysis was by AN OVA. Results: The results are expressed as mean weighted intragastric acidity (mmol/L). (i) Daytime (0-10 h postdose): when dosed with place bo 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 w ith ranitidine and cimetidine, respectively. Ranitidine inhibited weig hted intragastric acidity to a greater degree than cimetidine (P < 0.0 01) during this period. (ii) Night-time (10-20 h post-dose): when dose d with placebo the weighted intragastric acidity was 21.36 decreasing to 16.65 (P < 0.001 vs. placebo) when dosed with ranitidine and remain ing unchanged at 20.03 (P = 0.886 vs. placebo) when dosed with cimetid ine. Ranitidine inhibited weighted intragastric acidity to a greater d egree than cimetidine (P = 0.010) during this period. A sub-analysis o f the two 5-h intervals showed that compared to placebo, ranitidine in hibited weighted intragastric acidity significantly in the 10-15 h per iod. However, its effect in the 15-20 h period did not differ from pla cebo. Conclusions: In healthy subjects, the inhibitory effect of ranit idine 75 mg on intragastric acidity can be detected 10-15 h after an o ral dose. By contrast, the inhibitory effect of cimetidine 200 mg seem s to be restricted to the first 10 h.