Oral Bioavailability of Nizatidine and Ranitidine Concurrently Administered with Antacid

Abstract

This four-way crossover open-label study on eight healthy subjects was designed to investigate the effect on bioavailability of orally administered nizatidine given concurrently with an antacid (magnesium hydroxide–aluminium hydroxide mixture). Ranitidine was used as a comparison. Subjects were hospitalized overnight for each drug application which was given as a single dose [nizatidine or ranitidine (300 mg) or antacid (20 ml) of a neutralizing capacity of 50 mmol hydrochloric acid]. Plasma nizatidine or ranitidine concentrations were measured by high performance liquid chromatography. No statistically significant difference occurred in the kinetic profile of nizatidine after antacid administration although it took longer to reach maximum concentration in plasma. The area under the concentration–time curve was also reduced (by ≤10%) and there was a longer lag between administration and absorption. Bioequivalence (Westlake test) for ranitidine in the presence or absence of antacid was confirmed (difference ≤12%). For nizatidine, with or without antacid, the value of the Westlake test was just above the limit for bioequivalence (21.4%), whereas the Student's t-test for related means (one-tailed distribution) gave P = 0.045. There was no clinically relevant nizatidine–antacid interaction at the doses used in this study.