LOW-DOSE FAMOTIDINE AND EFFERVESCENT CIMETIDINE IN HEALTHY-SUBJECTS -A PLACEBO-CONTROLLED OVERNIGHT PH STUDY

Background: Amongst the low-dose H-2-receptor antagonists available fo r the self-medication of dyspepsia, both famotidine 10 mg and cimetidi ne 200 mg have been shown to raise intragastric pH, but there is a del ay after ingestion before significant effects can be demonstrated. A n ew effervescent preparation of cimetidine 200 mg releases an acid buff er which has a more rapid effect on intragastric pH. Aim: To investiga te the relative abilities of low-dose famotidine and effervescent cime tidine to raise intragastric pH after a single postprandial evening do se, Methods: Twenty-four healthy subjects (12 men, 12 women, median ag e 32 years) completed a three-period crossover trial of famotidine 10 mg, effervescent cimetidine 200 mg and placebo. After a standard meal was given at 18.30 h to subjects fasted for 5.5 h, drug or placebo was given at 19.30 h, Intragastric pH was recorded with combined glass el ectrodes from 18.00 to 07.30 h by digital recorders. Results: Over the 12 h post-dose period the mean area under the pH/time curve (AUC) aft er famotidine 10 mg was 3.73, after cimetidine 200 mg effervescent 2.7 9, and after placebo 2.07, Over the same period the median pH and perc entage of time that recordings were above pH 3 were 3.45 and 52.5 afte r famotidine 10 mg, 2.40 and 33.8 after cimetidine 200 mg effervescent , and 1.68 and 15.9 after placebo, Both active treatments were signifi cantly different from placebo by each measure (P < 0.001), and famotid ine 10 mg was significantly more effective than cimetidine 200 mg effe rvescent by each measure over the 0-12 h period (P < 0,001), Compariso ns of mean AUCs for each 15 min period after dosing showed that decrea se in acidity was significantly greater after cimetidine 200 mg efferv escent than after famotidine 10 mg for the first 60 min, In the later post-dose period only famotidine 10 mg raised pH for all time points t o 12 h, whilst the effect of effervescent cimetidine 200 mg was detect able to approximate to 8 h. Conclusions: Inhibition of gastric acidity over the 12 h post-dose period was significantly greater and endured longer after famotidine 10 mg than after effervescent cimetidine 200 m g, but for the 60 min period immediately after dosing the effect on in tragastric pH was significant following effervescent cimetidine 200 mg but not famotidine 10 mg. This suggests effervescent formulations of H-2-receptor antagonists with an acid buffer have a more rapid effect on intragastric pH than film-coated tablets.