Zaldaride Maleate (a New Calmodulin Antagonist) Versus Loperamide in the Treatment of Traveler's Diarrhea: Randomized, Placebo-Controlled Trial

The present study was undertaken to compare the efficacy of a new calmodulin antagonist, zaldaride maleate, with that of placebo or loperamide in persons with traveler's diarrhea. One hundred seventy-nine patients were randomized to receive loperamide(4 mg followed by 2 mg after each unformed stool), zaldaride maleate (20 mg four times per day), or placebo. During the initial 48 hours of therapy, zaldaride maleate decreased the number of unformed stools by 30 % and the duration of illnessby 23%when compared with placebo. Loperamidewas superior to both zaldaride maleate and placebo during the initial hours of treatment. However, after 48 hours of treatment, loperamide and zaldaride maleate were equally efficacious, decreasing by>50 % the number of unformed stools passed in a 24-hour interval (P, not significant), and were both superior when compared with placebo (P <.0001 and P =.0048, respectively). The apparent superiority of loperamide early in the course of therapy appeared to be related to a loading-dose effect and not to any differences in antidiarrheal properties. Zaldaride maleate, a pyrrolo-benoxazepine with calmodulin-inhibiting properties, has previously been shown to be an effec-tive agent when compared with placebo for the treatment of diarrhea during short-term travel in Mexico [1]. Currently available antimotility agents, including loperamide, decrease gastrointestinal transit time, which may be deleterious in the treatment of certain enteric infections [2]. Thus, a distinct ad-vantage of this novel inhibitor is its effective antidiarrheal activity due to its antisecretory properties, which does not inter-fere with gastrointestinal transit time [3]. The objectives of the present study were to confirm the efficacy of zaldaride maleate for the symptomatic relief of acute diarrhea and to compare its efficacy with that of loperamide, an agent with known antidiar-rheal activity [4]