CIMETIDINE PHARMACODYNAMICS AND PHARMACOKINETICS IN HEALTHY-SUBJECTS - A COMPARISON OF TABLETS AND SUSPENSION

The objective of this study was to compare the effect of cimetidine 20 0 mg tablet with that of cimetidine suspension (200 mg/10 mL), a 20 mL suspension of 800 mg magnesium hydroxide and 912 mg aluminum hydroxid e, and matching placebo on intragastric pH of healthy volunteers. Ther e were 13 males and seven females, mean age 23 years (range 20 to 32) and mean weight 72 kg (range 55 to 89). The intragastric pH of each su bject was measured over 6 h starting immediately before dosing on each of five study days. Cimetidine plasma levels were measured for 6 h af ter dosing on each of the cimetidine study days. Cimetidine tablet and suspension were superior to placebo tablet or suspension or to the ma gnesium hydroxide/aluminum hydroxide suspension in the area under the pH time curve from 0 to 6 h, percentage time pH of at least 3.5, chang e from pretreatment pH area under the pH time curve (0 to 6 h) and max imum increase in pH. Mean plasma cimetidine levels were significantly and positively correlated to mean intragastric pH for both cimetidine tablets and cimetidine suspension. Comparing cimetidine concentration (Cmax) and lower percentage time plasma cimetidine concentration was a t least 0.5 mug/mL (the minimum therapeutic level). These pharmacokine tic variations between cimetidine suspension and tablets may have part ially explained the pharmacodynamic differences of the lower area unde r the pH time curve (0 to 6 h). The results indicate that both cimetid ine tablets and cimetidine suspension significantly increase intragast ric pH relative to the magnesium hydroxide/aluminum hydroxide suspensi on, placebo tablets or placebo suspension. Based on the assumption tha t elevation of intragastric pH is an important factor for alleviation of the symptoms and for the healing of peptic disorders, the results o f this study suggest that both cimetidine tablets and cimetidine suspe nsion should be effective treatment.