montelukast and Dyspepsia

Functional dyspepsia (FD) is common in children, with as many as 80% of those being evaluated for chronic abdominal pain reporting symptoms of epigastric discomfort, nausea, or fullness. It is known that patients with persistent complaints have increased comorbidities such as depression and anxiety. The interaction with psychopathologic variables has been found to mediate the association between upper abdominal pain and gastric hypersensitivity. These observations suggest that abnormal central nervous system processing of gastric stimuli may be a relevant pathophysiologic mechanism in FD. Despite increased understanding, no specific therapy has emerged; however, recent nonpharmacological-based options such as hypnosis may be effective. Novel approaches, including dietary manipulation and use of nutraceuticals such as ginger and Iberogast (Medical Futures Inc., Ontario, Canada), may also be considered.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Abdominal Pain; Acetates; Acupuncture Therapy; Adolescent; Animals; Child; Cognitive Behavioral Therapy; Cyclopropanes; Dyspepsia; Endoscopy, Gastrointestinal; Gastric Emptying; Gastrointestinal Motility; Helicobacter Infections; Helicobacter pylori; Humans; Hypnosis; Imagery, Psychotherapy; Lansoprazole; Leukotriene Antagonists; Phytotherapy; Plant Extracts; Proton Pump Inhibitors; Quinolines; Serotonin; Stomach; Sulfides; Viscera; Zingiber officinale

We have previously demonstrated the clinical efficacy of montelukast in a randomized double-blind controlled cross-over trial in patients with dyspepsia in association with duodenal eosinophilia. The mechanism of this clinical response is unknown but could involve a decrease in eosinophil density or activation.. Twenty-four dyspeptic patients 8-17 years of age underwent initial blood sampling and endoscopy with biopsy. Eighteen of these patients had elevated duodenal eosinophil density and underwent repeat blood sampling and endoscopy following 21 days of therapy with montelukast (10 mg/day). The following were determined: global clinical response on a 5-point Lickert-type scale, eosinophil density utilizing H & E staining, eosinophil activation determined by degranulation indices on electron microscopy, and serum cytokine concentrations. On day 21, pharmacokinetics and duodenal mucosal drug concentrations were determined.. Eighty-three percent of the patients had a positive clinical response to montelukast with regard to relief of pain with 50% having a complete or nearly complete clinical response. The response was unrelated to systemic drug exposure or to mucosal drug concentration. Other than a mild decrease in eosinophil density in the second portion of the duodenum, there were no significant changes in eosinophil density, eosinophil activation, or serum cytokine concentrations following treatment with montelukast. Pre-treatment TNF-alpha concentration was negatively correlated with clinical response.. The short-term clinical response to montelukast does not appear to result from changes in eosinophil density or activation. Whether the effect is mediated through specific mediators or non-inflammatory cells such as enteric nerves remains to be determined.. ClinicalTrials.gov; NCT00148603.

Topics: Acetates; Adolescent; Biopsy; Cell Count; Child; Cyclopropanes; Cytokines; Dose-Response Relationship, Drug; Duodenum; Dyspepsia; Eosinophilia; Eosinophils; Female; Humans; Intestinal Mucosa; Leukotriene Antagonists; Male; Quinolines; Sulfides; Treatment Outcome

Montelukast, a competitive cysteinyl leucotriene-1 receptor antagonist, reduces airway eosinophilia in asthmatics. We evaluated the effect of this drug in children with eosinophilic duodenitis, defined histologically as duodenal mucosa with peak eosinophil count of more than 10 eosinophils/hpf.. Forty children and adolescents (6-18 yr) with dyspepsia and duodenal eosinophilia were enrolled in a double blind, randomized, placebo-controlled, cross-over study of monteleukast therapy. Subjects were randomized to receive either 10 mg montelukast or an identical placebo once daily and were evaluated on day 14 for symptomatic and biochemical responses. Subjects were also randomized to one of two blood sampling schemes to evaluate montelukast pharmacokinetics.. Using a post treatment global pain assessment, a positive clinical response was observed in 62.1% of patients receiving montelukast compared with 32.4% on placebo (p < 0.02). Pain assessment score deteriorated in 45% of montelukast responders (5/11) after cross-over to placebo and improved in 62% (8/13) of placebo non-responders on cross-over to montelukast. In patients with peak duodenal eosinophil counts between 20-29/hpf (n=19), a positive pain assessment response was observed in 84% of patients receiving montelukast compared to 42% receiving placebo (p < 0.01). Response rate did not differ by age, gender or histologic findings at baseline. Pharmacokinetic analysis yielded parameter estimates for absorption rate constant (Ka), apparent volume of distribution (Vd/F) and elimination rate constant (Kel) of 0.42 h, 0.19 L/kg and 0.26 h, respectively. The relative extent of systemic drug exposure was comparable to that observed in previous pediatric investigations with similar weight-adjusted montelukast doses. Neither dose nor calculated drug exposure were associated with the level of post treatment pain assessment or the change in biochemical markers.. These data suggest a beneficial role for montelukast in the treatment of pediatric patients with dyspepsia associated with duodenal eosinophilia.

Topics: Acetates; Adolescent; Child; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Duodenal Diseases; Dyspepsia; Eosinophilia; Female; Humans; Intestinal Mucosa; Leukotriene Antagonists; Male; Pain; Quinolines; Sulfides; Treatment Outcome