Low-dose famotidine and effervescent cimetidine in healthy subjects: a placebo-controlled overnight pH study.
BACKGROUND
Amongst the low-dose H2-receptor antagonists available for the self-medication of dyspepsia, both famotidine 10 mg and cimetidine 200 mg have been shown to raise intragastric pH, but there is a delay after ingestion before significant effects can be demonstrated. A new effervescent preparation of cimetidine 200 mg releases an acid buffer which has a more rapid effect on intragastric pH.


OBJECTIVE
To investigate the relative abilities of low-dose famotidine and effervescent cimetidine to raise intragastric pH after a single postprandial evening dose.


METHODS
Twenty-four healthy subjects (12 men, 12 women, median age 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 electrodes 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) after famotidine 10 mg was 3.73, after cimetidine 200 mg effervescent 2.79, and after placebo 2.07. Over the same period the median pH and percentage of time that recordings were above pH 3 were 3.45 and 52.5 after 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 significantly different from placebo by each measure (P < 0.001), and famotidine 10 mg was significantly more effective than cimetidine 200 mg effervescent by each measure over the 0-12 h period (P < 0.001). Comparisons of mean AUCs for each 15 min period after dosing showed that decrease in acidity was significantly greater after cimetidine 200 mg effervescent 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 to 12 h, whilst the effect of effervescent cimetidine 200 mg was detectable 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 mg, but for the 60 min period immediately after dosing the effect on intragastric pH was significant following effervescent cimetidine 200 mg but not famotidine 10 mg. This suggests effervescent formulations of H2-receptor antagonists with an acid buffer have a more rapid effect on intragastric pH than film-coated tablets.
Reilly
T G
TG
Department of Gastroenterology, Walsgrave Hospital, Coventry, UK.
Grimley
C E
CE
Usselmann
B
B
Cottrell
J
J
Mann
S G
SG
Raskin
S
S
Nwokolo
C U
CU
D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D002927:Cimetidine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D015738:Famotidine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D005744:Gastric Acid / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D019999:Pharmaceutical Solutions
D000897:Anti-Ulcer Agents; D019999:Pharmaceutical Solutions; D015738:Famotidine; D002927:Cimetidine