| Abstract: | The effectiveness of intravenous nizatidine in suppressing gastric acid secretion was evaluated by different methods of inducing secretion in two single-blind studies. In study 1, seven subjects were given single, 20-min intravenous infusions of nizatidine (6.25, 25, 75, 150, or 250 mg) before modified sham feeding (MSF). Gastric acid suppression after nizatidine was contrasted with that after placebo and MSF. All doses of nizatidine reduced secretion; the 150- and 250-mg doses of nizatidine suppressed secretion for at least 2.5 hr. In study 2, eight subjects received one 5-min intravenous infusion of placebo, cimetidine (300 mg), or nizatidine (25, 50, 100, or 250 mg) weekly for 6 wk. Secretion was induced by infusing pentagastrin (2 micrograms/kg/hr) 45 min before the study drug was dosed and for 3.5 hr thereafter. Again, all doses of nizatidine reduced gastric acid, chiefly by decreasing volume. Nizatidine induced a clear dose-response effect; nizatidine (100 mg) and cimetidine (300 mg) had approximately equal suppressive effects. Nizatidine (100 mg) and cimetidine (300 mg) reduced acid output by 62% and 63% and reduced volume of secretion by 48% and 51% over the 3.5-hr period. Gastric acid suppression and plasma nizatidine concentrations were directly related. Nizatidine kinetics were linear and proportional to dose. The t1/2 was 1.3 hr (range 0.7 to 2.1 hr), the volume of distribution was 1.2 +/- 0.5 l/kg, and clearance was 0.6 +/- 0.2 l/kg/hr. Laboratory abnormalities and side effects were minor in both studies. |
