The effect of cimetidine, a new histamine H2-receptor antagonist, on gastric acid secretion stimulated by a homogenised meal was studied in six normal volunteers using an in vivo intragastric titration technique. The subjects were studied twice, no more than 48 h apart, receiving either cimetidine 200 mg or placebo in random order. Cimetidine administered either 32 men before (three subjects) or with the meal (three subjects) significantly inhibited gastric acid secretion in all the subjects throughout the period of study; 96 min after food, total acid secretion decreased by 67 and 57% respectively. When the drug was taken with the meal absorption was slower (mean peak blood level 2-34 mumol/l, 80-128 min after dosing) than when administered on an empty stomach (mean peak blood level 5-08 mumol/l, 48-64 min after dosing). Blood cimetidine concentration correlated significantly (P less than 0-01) with percentage inhibition of acid output and the calculated concentration resulting in 50% inhibition of gastric acid secretion (IC50) was 1-6 mumol/l. Secretion of gastrin in response to food was unaffected by cimetidine. The results suggest that 200 mg cimetidine effectively inhibits food-stimulated acid secretion and that the bioavailability of the drug may be affected by the timing of dosage in relation to meals. No unwanted effect were observed.
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