Early and late effects of low-dose famotidine, ranitidine or placebo on pentagastrin-stimulated gastric acid secretion in man.
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 microgram.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 pH7 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.
Department of Gastroenterology, Walsgrave Hospital, Coventry, UK.
C E
CE
Grimley
J M
JM
West
D E
DE
Loft
J
J
Cottrell
S G
SG
Mann
L
L
Stauffer
C U
CU
Nwokolo
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018592:Cross-Over Studies; D015738:Famotidine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D016480:Helicobacter pylori / Q000187:drug effects; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010418:Pentagastrin / Q000008:administration & dosage / Q000009:adverse effects; D010437:Peptic Ulcer / Q000188:drug therapy; D011899:Ranitidine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D015738:Famotidine; D011899:Ranitidine; D010418:Pentagastrin