title: Impact of a soluble phospholipase A2 inhibitor on inhaled allergen challenge in subjects with asthma.
abstract: The possible roles of secretory phospholipases A2 (sPLA2) in asthma include the release of arachidonic acid from cellular membranes, generation of lysophospholipids, sPLA2-mediated activation of cPLA2 with increased leukotriene production, and surfactant degradation. LY333013 is a potent inhibitor of sPLA2. This study examined the impact of two doses of LY333013 vs. placebo on allergen-induced bronchoconstriction following inhaled allergen challenge in atopic asthmatics. Fifty subjects were randomly assigned to treatment, and 40 subjects completed the study. A double-blind, placebo-controlled, random order, crossover study design was used. LY333013 had no impact on the primary outcome variables of the areas under the FEV1 response curve early (0-3 hours) (AUC(early)) and late (3-8 hours) (AUC(Iate)) following inhaled allergen challenge. No significant drug-related adverse effects were observed. The response to inhaled allergen challenge was reproducible and confirms the utility of this technique as a model in which to screen compounds for further testing in asthmatic patients.
authors.affiliation: Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1009, USA. dbowton@wfubmc.edu
authors.forename: David L
authors.initials: DL
authors.lastname: Bowton
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Dmitrienko
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.forename: Bernhardt G
authors.initials: BG
authors.lastname: Zeiher
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Sides
mesh_terms: D000085:Acetates / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007651:Keto Acids; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D012882:Skin Tests
chemical_list: D000085:Acetates; D007211:Indoles; D007651:Keto Acids; C117948:varespladib; D010741:Phospholipases A; D054467:Phospholipases A2