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 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.
Grimley
C E
CE
Department of Gastroenterology, Walsgrave Hospital, Coventry, UK.
Constantinides
S
S
Snell
C C
CC
Mills
J G
JG
Nwokolo
C U
CU
D000328:Adult; D002927:Cimetidine / Q000494:pharmacology; D018592:Cross-Over Studies; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D004366:Nonprescription Drugs / Q000494:pharmacology*; D010919:Placebos / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology*; D013997:Time Factors
D006635:Histamine H2 Antagonists; D004366:Nonprescription Drugs; D010919:Placebos; D002927:Cimetidine; D011899:Ranitidine