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

Okhuysen, Pablo C.; DuPont, Herbert L.; Ericsson, Charles D.; Marani, Salma K.; Martínez-Sandoval, Francisco; Olesen, Mikkel Runge; Ravelli, G. P.

doi:10.1093/clinids/21.2.341

Cited by 31 publications

(12 citation statements)

References 8 publications

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“…Zaldaride is a calmodulin-inhibiting drug that has antisecretory properties related to intracellular concentrations of calcium ( 100 ). Th e drug signifi cantly shortened the stools passed in subjects studied with TD compared with placebo therapy ( 96,101,102 ). Racecadotril, a specifi c enkephalinase inhibitor that prevents degradation of the endogenous antisecretory peptide neurotransmitter enkephalins that inhibit cyclic nucleotide secretory pathways without eff ect on gut motility ( 103 ) and has been used successfully in pediatric diarrhea ( 104 ).…”

Section: Recommendationmentioning

confidence: 99%

ACG Clinical Guideline: Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults

Riddle

DuPont

Connor

2016

American Journal of Gastroenterology

328

250

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Acute diarrheal infections are a common health problem globally and among both individuals in the United States and traveling to developing world countries. Multiple modalities including antibiotic and non-antibiotic therapies have been used to address these common infections. Information on treatment, prevention, diagnostics, and the consequences of acute diarrhea infection has emerged and helps to inform clinical management. In this ACG Clinical Guideline, the authors present an evidence-based approach to diagnosis, prevention, and treatment of acute diarrhea infection in both US-based and travel settings. Am J Gastroenterol 2016; 111:602-622; doi: 10.1038/ajg.2016 A follow-up survey where 3,568 respondents (median age 51) were asked at random about illness in the previous 7 days or previous month found that recall bias had an important eff ect on estimates of acute gastrointestinal illness ( 10 ). Using a 7-day exposure window, the estimated incidence of acute diarrhea was 1.6 episodes per person-year, compared with 0.9 episodes per person-year if asked about illness within the preceding month. Other population-based studies from Canada and western European countries using varied methodologies estimate annual incidence between 0.1 to 3.5 episodes per person-year ( 11 18. Antibiotic chemoprophylaxis has moderate to good effectiveness and may be considered in high-risk groups for short-term use. (Strong recommendation, high level of evidence) TD, traveler's diarrhea.

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Section: Recommendationmentioning

confidence: 99%

ACG Clinical Guideline: Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults

Riddle

DuPont

Connor

2016

American Journal of Gastroenterology

328

250

View full text Add to dashboard Cite

show abstract

“…It was evaluated in phase III randomized controlled trials in which effi cacy was demonstrated. However, future development was discontinued because of no additional benefi t compared with standard antidiarrheal agents [75,76] . In addition, there was evidence that zaldaride had some unwanted cardiovascular effects when used at the upper end of the therapeutic dosage range for acute diarrhea.…”

Section: Calcium-calmodulin Antagonistsmentioning

confidence: 99%

Antisecretory Drugs for Diarrheal Disease

Farthing

2006

Dig Dis

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Acute diarrhea is a major cause of morbidity and mortality worldwide. Infants and pre-school children are the most vulnerable in whom there are 2–3 million deaths each year as a result of the associated dehydration and acidosis. Although oral rehydration therapy has reduced mortality during the past 30 years ago, the search for agents that will directly inhibit intestinal secretory mechanisms and thereby reduce faecal losses in patients with high-volume watery diarrhea has continued for more than 20 years. A variety of potential targets for antisecretory agents have been explored which include loci within the enterocyte (the chloride channel, calcium-calmodulin) and other sites such as enteric nerves and endogenous mediators (such as 5-HT, prostaglandins). Although the potential of calcium-calmodulin inhibition has as yet not been realised, preliminary studies suggest that there are chloride channel blockers under development that will find a place in the management of secretory diarrheas. Recent work has highlighted the importance of neurohumoral mechanisms in the pathogenesis of acute diarrhea. Potentiation of the effects of endogenous enkephalin activity by enkephalinase inhibition has already produced a safe, effective anti-secretory drug, racecadotril. Speculative early work indicates that there may be a role for antagonists of 5-HT, substance P, and VIP receptors. There now seems to be a real possibility that antisecretory therapy will become more widely available in the future.

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“…Other ‘purely antisecretory’ agents for treatment of TD include zaldaride maleate (a potent and selective calmodulin inhibitor) [36] and racecadotril (an enkephalinase inhibitor) [37]. Both these compounds are devoid of any effect on gastrointestinal motility and their use is not followed by treatment-related rebound constipation.…”

Section: Treatmentmentioning

confidence: 99%

Prevention and Treatment of Traveler’s Diarrhea

et al. 2006

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Diarrhea, mostly due to bacterial infection of the gut, is the most frequent health complaint in the international traveler, affecting 20–70% of the traveling population depending on the destination and other factors. It is usually benign and self-limiting in nature, but symptoms may occasionally be distressing causing modifications of normal activities and sometimes confinement to bed or hospitalization. Prevention of traveler’s diarrhea should ideally be based on dietary restrictions, but experience shows that this target is extremely difficult to achieve. Antibiotic chemoprophylaxis should be restricted to selected groups of travelers at risk of severe complications of diarrhea or when diarrhea-driven alterations of planned activities are highly undesirable (crit- ical trips). The effectiveness of alternative prophylactic approaches, such as vaccination or the use of probiotics, still awaits confirmation. Treatment of mild diarrheal cases without intestinal symptoms may be limited to rehydration with or without antimotility agents. When antibiotic therapy is considered, non-absorbable antibiotics, such as rifaximin, may be considered a valid alternative to systemic antibiotics to treat uncomplicated cases, leaving fluoroquinolones and/or azithromycin for use in more severe cases or when invasive pathogens are suspected. Indeed, therapeutic use of doxycycline and trimethoprim-sulfamethoxazole (TMP-SMX) is limited by widespread resistance of many enteropathogens. The addition of loperamide or other antimotility agents usually provides symptom relief and further shortens the duration of illness and may be therefore safely adopted in the healthy adult unless dysentery is present.

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

Cited by 31 publications

References 8 publications

ACG Clinical Guideline: Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults

ACG Clinical Guideline: Diagnosis, Treatment, and Prevention of Acute Diarrheal Infections in Adults

Antisecretory Drugs for Diarrheal Disease

Prevention and Treatment of Traveler’s Diarrhea

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