EFFECT OF INCREASING GASTRIC PH WITH FAMOTIDINE ON THE ABSORPTION ANDORAL PHARMACOKINETICS OF THE INOTROPIC AGENT VESNARINONE

The effect of famotidine, an H2 receptor blocker, on the oral absorpti on and pharmacokinetics of the novel agent vesnarinone was investigate d after oral administration of 60 mg vesnarinone with and without pret reatment with intravenous famotidine. The single-blind, randomized, tw o-way crossover study was conducted in 12 volunteers, with a washout p eriod of 7 days between the two treatments. A pH monitor was used to e nsure that gastric pH of the subjects was less than or equal to 3 in t he absence of and greater than or equal to 5 in the presence of famoti dine. A significant decrease in maximum concentration (C-max) and incr ease in time to C-max (t(max)) was observed for vesnarinone during tre atment with famotidine, whereas area under the concentration-time curv e (AUC) was similar for both treatments. The physicochemical propertie s of the drug support the above observations. Therefore, therapies tha t increase gastric pH will affect the rate but not the extent of absor ption of vesnarinone or the safety or efficacy profile of vesnarinone. (C) 1998 The American College of Clinical Pharmacology.