Abstract

Trimoprostil, a prostaglandin E2 analog, was evaluated to determine if there was a relationship between plasma concentrations and inhibition of histamine-stimulated gastric acid secretion in dogs prepared with Heidenhain pouches. Trimoprostil was given p.o. followed by collection (drainage) of gastric juice from the pouch to determine acid output. In addition, serial blood samples were withdrawn to determine trimoprostil plasma concentrations. Trimoprostil was absorbed rapidly and eliminated with T1/2 ranging from 25 to 37 min. Trimoprostil was effective in inhibiting acid output compared with control. The maximal response and duration of activity were dependent on the concentration-time profile of trimoprostil. Trimoprostil produced a maximum inhibition of 98% and suppressed acid output for at least 3 hr. When plasma concentrations were related to the antisecretory response using a modified Hill equation, the response was found to lag behind plasma concentrations as evidenced by hysteresis loops. The predicted plasma concentration associated with a 50% inhibition of acid secretion (IC50) ranged from 0.58 to 0.79 ng/ml.