The efficacy of BW942C, a novel enkephalinlike pentapeptide antidiarrheal agent, was compared with the efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) and the combination of the two agents in a placebocontrolled trial of the 72-h treatment of acute diarrhea. Subjects with diarrhea but without bloody stools or fever greater than 102°F (38.9°C) were enrolled. Administered to 134 U.S. adults with diarrhea that developed shortly after their arrival in Guadalajara, Mexico, BW942C was more efficacious than TMP-SMX in relieving diarrhea and cramps in the first 12 h of therapy, especially among subjects with diarrhea caused by enterotoxigenic E. coli. In the BW942C treatment group, 25% of subjects eventually took additional therapy because their diarrhea did not respond to BW942C alone. Neurological side effects such as dizziness and light-headedness occurred more frequently among BW942C-treated subjects. Therapy for 3 days with TMP-SMX provided lasting relief comparable with previously reported 5-day therapy. Use of the combination of both agents provided the benefits of prompt relief afforded by BW942C and lasting relief afforded by TMP-SMX. BW942C might prove to be an agent suitable for the treatment of acute diarrhea, with TMP-SMX reserved for treatment of those who do not respond adequately. The empiric use of the combination of BW942C and TMP-SMX appears appropriate for the treatment of severe nondysenteric disease.BW942C is a novel, enkephalinlike pentapeptide [Tyr-DMet-(0)-Gly-pNO2-Phe-Pro-NH2 acetate] with demonstrated antidiarrheal properties in animal models and proven antisecretory activity against enterotoxins of Escherichia coli and Vibrio cholerae (10). In preliminary animal studies, BW942C appears to have a low abuse potential, limited effects on the central nervous system, a high therapeutic index, and a rapid onset' of action. In volunteers with castor oil-induced diarrhea, treatment with BW942C compared with placebo led to a decrease in overall stool frequency, abdominal cramping, nausea, and vomiting. The only adverse effects noted were dizziness and dry mouth that occurred more frequently at high dosages (J. Ryan, J.Leighton, D. Kirksey, and G. McMahon, Clin. Pharmacol.Ther., in press).This report examines the efficacy and safety of BW942C used alope as an antidiarrheal agent or in combination with an antibiotic, trimethoprim-sulfamethoxazole (TMP-SMX). The hypothesis was that use of BW942C might prove efficacious compared with placebo and that use of the agent in combination with TMP-SMX might afford earlier relief of diarrhea than is already possible with use of TMP-SMX alone. Although in a previous study TMP-SMX was given for 5 days (5), we administered it for only 3 days in this study in an effort to define a more cost-effective use of this antibiotic.
MATERIALS AND METHODSA total of 134 male and female students, newly arrived in Guadalajara, Mexico, from the United States, were enrolled in a prospective, randomized, double-blind study during the summer of 1983. Subjects who presented to the...