EFFECT OF NIZATIDINE AND RANITIDINE ON 24-HOUR INTRAGASTRIC PH, PEPSIN, PROSTAGLANDIN E(2) AND SERUM GASTRIN-CONCENTRATIONS IN HEALTHY-VOLUNTEERS

In order to achieve possible greater therapeutic efficacy, ranitidine 300 mg bid (R(2)) may be given rather than 300 mg qhs (R(1)), or nizatidine 300 mg bid (N-2) may be given rather than 300 mg qhs (N-1). A randomized placebo-controlled crossover study was performed in six healthy volunteers (four males, two females) who ranged in age from 23 to 43 years, comparing R(1), R(2), N-1 and N-2 versus placebo (P), measuring 24 h intragastric pH by the aspiration technique, gastric juice pepsin and prostaglandin E(2) (PGE(2)) concentrations, as well as serum gastrin concentrations. In all treatment groups, 24-h intragastric pH was higher than with P; the 24 h and daytime (0800-2200 h) pH was higher with N-2 than with N-1, but not with R(2) versus R(1). The percentage pH greater than or equal to 3 was greater with N-2 than with N-2 during the daytime. Night-time (2200-0800 h) and 24 h pepsin concentrations were higher in R(2) than in R(1), were similar in N-1 and N-2, and were lower in these treatment groups than in P. The gastric juice PGE(2) concentration at night-time, but not at daytime, was increased in the four treatment groups compared with P. Despite the higher pH values at night-time in the treatment groups, the night-time concentrations of serum gastrin were unchanged, and yet-during the daytime the higher values of pH were associated with increased gastrin concentrations when R(2) or N-2 were given, but not with R(1) and N-1. There was a negative correlation between intragastric juice pH and pepsin concentration during the daytime, and a positive correlation between pH and PGE(2) concentration during the night-time. The slopes and y-axis intercepts between pH and pepsin or PGE(2) concentrations differed between the placebo and the treatment groups, suggesting that these H-2-receptor antagonists may have an effect on lowering pepsin and raising PGE(2) concentrations in addition to their effects on pH. As the percentage of time over the 24 h period and night-time periods when the pH was greater than 3 was not different between ranitidine and nizatidine, the two regimens will likely have similar clinical efficacy.