title: Worldwide clinical experience with the first marketed leukotriene receptor antagonist.
abstract: Pranlukast (SB 205312, ONO-1078) is an orally active, potent, selective blocker of peptidyl-leukotriene receptors. Pranlukast has been studied in a worldwide clinical development program and recently was approved in Japan for the treatment of asthma. This worldwide experience includes a pivotal safety and efficacy study conducted in Japan, a leukotriene D4 (LTD4) challenge study conducted in Europe, and two safety, tolerability, and clinical activity studies conducted in Europe and North America. The pivotal study was a randomized, double-blind, 8-week comparison of pranlukast, 225 mg bid, and azelastine, 2 mg bid. Improvements in asthma symptom scores, morning and evening peak expiratory flow rate (PEFR), and a decreased need for bronchodilators and corticosteroids in the pranlukast-treated group were statistically significant when compared with those in the azelastine-treated group. The most common adverse experiences were GI. The European challenge study evaluated the ability of 5-day therapy with pranlukast, 450 mg bid, to block the bronchoconstrictor effect of inhaled LTD4. A single dose of pranlukast resulted in a 10.6-fold increase in the concentration of LTD4 required to produce a 35% decrease in specific airways conduction; following 5 days of therapy, this increased to 25.9-fold. The two safety, tolerability, and clinical activity studies were randomized, double-blind, placebo-controlled, 4-week evaluations of pranlukast, 225 to 450 mg bid. Improvements in FEV1, PEFR, and asthma symptoms were noted. Ongoing studies will define further the role of pranlukast as a treatment for asthma and allergic rhinitis.
authors.affiliation: Department of Respiratory Medicine, London Chest Hospital, UK.
authors.forename: N C
authors.initials: NC
authors.lastname: Barnes
authors.forename: B
authors.initials: B
authors.lastname: de Jong
authors.forename: T
authors.initials: T
authors.lastname: Miyamoto
mesh_terms: D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002867:Chromones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D005060:Europe; D006801:Humans; D007564:Japan; D020024:Leukotriene Antagonists; D009656:North America
chemical_list: D018927:Anti-Asthmatic Agents; D002867:Chromones; D020024:Leukotriene Antagonists; C047681:pranlukast