Clinical efficacy and pharmacokinetics of montelukast in dyspeptic children with duodenal eosinophilia.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These data suggest a beneficial role for montelukast in the treatment of pediatric patients with dyspepsia associated with duodenal eosinophilia.
Friesen
Craig A
CA
Section of Gastroenterology, The Children's Mercy Hospital and Clinics, Kansas City, Missouri 64108, USA. cfriesen@cmh.edu
Kearns
Gregory L
GL
Andre
Linda
L
Neustrom
Mark
M
Roberts
Charles C
CC
Abdel-Rahman
Susan M
SM
D000085:Acetates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000293:Adolescent; D002648:Child; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004311:Double-Blind Method; D004378:Duodenal Diseases / Q000188:drug therapy* / Q000378:metabolism; D004415:Dyspepsia / Q000188:drug therapy* / Q000378:metabolism; D004802:Eosinophilia / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology; D020024:Leukotriene Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D010146:Pain / Q000209:etiology; D011804:Quinolines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013440:Sulfides; D016896:Treatment Outcome
D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; C093875:montelukast