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Management of Asthma with Zafirlukast

Clinical Experience and Tolerability Profile

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Summary

This article reviews the literature on the use of zafirlukast in the treatment of asthma, with particular focus on its ability to attenuate the asthma-causing effects of leukotrienes.

Leukotrienes produced by the 5-lipoxygenase enzyme pathway have various biological activities. These include the specific inflammatory effects associated with asthma, such as increased vascular permeability, enhanced mucus production and decreased mucociliary transport. Leukotriene receptors in the airways also mediate a potent bronchoconstriction and this is particularly important in asthma. Zafirlukast was developed with the goal of attenuating the inflammatory effects of leukotrienes in asthma.

Zafirlukast attenuates the responses to inhaled leukotrienes and allergen challenges, and produces beneficial effects in cold air- and exercise-induced asthma. Zafirlukast has been compared with placebo and sodium cromoglycate in clinical trials involving asthma patients. Zafirlukast brings about a significant bronchodilation within 1 hour of administration that is additive to the effects of β2 agonists. These studies showed that zafirlukast improves pulmonary function and reduces the symptoms of asthma. Zafirlukast is well tolerated with an incidence of adverse events similar to that seen with the use of placebo. As an oral twice-daily formulation, zafirlukast may improve patient adherence to therapy. As an anti-inflammatory agent, zafirlukast may in the future find a role in the treatment of a variety of diverse inflammatory conditions.

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References

  1. Feldberg W, Kellaway CH. Liberation of histamine and formation of lysocithin-like substances by cobra venom. J Physiol 1938; 94: 187–226

    PubMed  CAS  Google Scholar 

  2. Kellaway CH, Trethewie RE. The liberation of a slow reacting smooth muscle stimulating substance of anaphylaxis. J Exp Physiol 1940; 30: 121–45

    CAS  Google Scholar 

  3. Samuelsson B. Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science 1983; 220: 568–75

    Article  PubMed  CAS  Google Scholar 

  4. Henderson WRJ. Eicosanoids and lung inflammation. Am Rev Respir Dis 1987; 135: 1176–85

    PubMed  CAS  Google Scholar 

  5. Executive Summary. Guidelines for the diagnosis and management of asthma. In: National Institutes of Health Expert Panel Report: publication no. 91-3042, 1991; Bethesda, Maryland: 1-136

  6. Spector SL, Nicklas RA, editors. Practice parameters for the diagnosis and treatment of asthma. J Allergy Clin Immunol 1995; 96 Suppl.: 707–858

    Google Scholar 

  7. Drazen JM, Austen KF, Lewis RA, et al. Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro. Proc Natl Acad Sci USA 1980; 77: 4354–8

    Article  PubMed  CAS  Google Scholar 

  8. Rinkema LE, Bemis KG, Fleish JH. Production and antagonism of cutaneous vascular permeability in the guinea pig in response to histamine, leukotrienes, and A23187. J Pharmacol Exp Ther 1984; 230: 550–7

    PubMed  CAS  Google Scholar 

  9. Marom Z, Shelhamer JH, Bach MK, et al. Slow-reacting substances, leukotrienes LTC4 and LTD4, increase the release of mucus from human airways in vitro. Am Rev Respir Dis 1982; 126: 449–51

    PubMed  CAS  Google Scholar 

  10. Drazen JM. Inhalation challenge with sulfidopeptide leukotrienes in human subjects. Chest 1986; 89: 414–9

    Article  PubMed  CAS  Google Scholar 

  11. Ford-Hutchinson AW, Evans JE Leukotriene B4: biologic properties and regulation of biosynthesis. In: Piper PJ, editor. The leukotrienes: their biological significance. New York: Raven Press, 1986: 141–50

    Google Scholar 

  12. Goldman DW. Regulation of the receptor system for leukotriene B4 on human neutrophils. Ann NY Acad Sci 1988; 524: 187–95

    Article  PubMed  CAS  Google Scholar 

  13. Schuil PJ, van Gelder JM, ten Berge M, et al. Histamine and leukotriene C4 effects on in vitro ciliary beat frequency of human upper respiratory cilia. Eur Arch Otorhinolaryngol 1994; 251: 325–8

    Article  PubMed  CAS  Google Scholar 

  14. Dahlen S-E, Hansson G, Hedqvist P, et al. Allergen challenge of lung tissue from asthmatics elicits bronchial contraction that correlates with release of leukotrienes C4, D4, and E4. Proc Natl Acad Sci USA 1983; 80: 1712–6

    Article  PubMed  CAS  Google Scholar 

  15. Hedqvist P, Dahlen S-E, Gustafsson L, et al. Biological profile of leukotrienes C4 and D4. Acta Physiol Scand 1980; 110: 331–3

    Article  PubMed  CAS  Google Scholar 

  16. Fabbri LM, Boschetto P, Zocca E, et al. Bronchoalveolar neutrophilia during late asthmatic reactions induced by toluene diisocyanate. Ann Rev Respir Dis 1987; 136(1): 36–42

    Article  CAS  Google Scholar 

  17. Bousquet J, Chanez P, Lacoste JY, et al. Eosinophilic inflammation in asthma. N Eng J Med 1991; 324: 1514–5

    Google Scholar 

  18. Buckner CK, Fedyna JS, Robertson JL, et al. An examination of the influence of the epithelium on contractile responses to peptidoleukotrienes and blockade by ICI 204,219 in isolated guinea-pig trachea and human intralobar airways. J Pharmacol Exp Ther 1989; 252: 77–85

    Google Scholar 

  19. Chanarin N, Johnston SL. Leukotrienes as a target in asthma therapy. Drugs 1994; 47: 12–24

    Article  PubMed  CAS  Google Scholar 

  20. Smith LJ, Geller S, Ebright L, et al. Inhibition of leukotriene D4-induced bronchoconstriction in normal subjects by the oral LTD4 receptor antagonist ICI 204,219. Am Rev Respir Dis 1990; 141: 988–92

    Article  PubMed  CAS  Google Scholar 

  21. Smith LJ, Glass M, Minkwitz MC. Inhibition of leukotriene D4-induced bronchoconstriction in subjects with asthma: a concentration-effect study of ICI-204,219. Clin Pharmacol Ther 1993; 54: 430–6

    Article  PubMed  CAS  Google Scholar 

  22. Schellenberg RR, Walker B. Platelet-dependent contraction of human bronchus by platelet-activating factor. J Allergy Clin Immunol 1983; 71: 154

    Article  Google Scholar 

  23. Taylor IK, Ward PS, Taylor GW, et al. Inhaled PAF stimulates leukotriene and thromboxane A2 production in humans. J Appl Physiol 1991; 71: 1396–402

    PubMed  CAS  Google Scholar 

  24. Kidney JC, Ridge SM, Chung KF, et al. Inhibition of platelet-activating factor-induced bronchoconstriction by the leukotriene D4 receptor antagonist, ICI 204,219. Am Rev Respir Dis 1993; 147: 215–7

    Article  PubMed  CAS  Google Scholar 

  25. Taylor IK, O’Shaughnessy KM, Fuller RW, et al. Effect of cysteinyl-leukotriene receptor antagonist ICI 204,219 on allergen induced bronchoconstriction and airways hyperreactivity in atopic subjects. Lancet 1991; 337: 690–4

    Article  PubMed  CAS  Google Scholar 

  26. Findlay SR, Barden JM, Easley CB, et al. Effect of the oral leukotriene antagonist, ICI-204,219, on antigen-induced bronchoconstriction in subjects with asthma. J Allergy Clin Immunol 1992; 89: 1040–5

    Article  PubMed  CAS  Google Scholar 

  27. Dahlen B, Zetterstrom O, Bjorck T, et al. The leukotriene-antagonist ICI-204, 219 inhibits the early airway reaction to cumulative bronchial challenge with allergen in atopic asthmatics. Eur Respir J 1994; 7: 324–31

    Article  PubMed  CAS  Google Scholar 

  28. O’Shaughnessy KM, Taylor IK, O’Connor B, et al. Potent leukotriene D4 receptor antagonist ICI 204,219 given by the inhaled route inhibits the early but not the late phase response of allergen-induced bronchoconstriction. Am Rev Respir Dis 1993; 147: 1431–5

    PubMed  Google Scholar 

  29. Nathan RA, Glass M, Minkwitz MC. Inhaled ICI 204,219 blocks antigen-induced bronchoconstriction in subjects with bronchial asthma. Chest 1994; 105: 483–8

    Article  PubMed  CAS  Google Scholar 

  30. Calhoun WJ, Lavins BJ, Glass M. Effect of ‘Accolate’ (zafirluk-ast) on bronchoalveolar lavage fluid (BAL) after segmental bronchoprovocation (SBP) in patients with mild to moderate asthma [abstract]. Am J Respir Crit Care Med 1995; 151: A42

    Google Scholar 

  31. Lazarus SC, Lavins BJ, Wong HH, et al. Effect of oral Accolate (zafirlukast) on sulfur dioxide (SO2)-induced bronchoconstriction in patients with asthma [abstract]. Am J Respir Crit Care Med 1995; 151: A41

    Google Scholar 

  32. Juniper EF, Kline PA, Vanzielehgem MA, et al. Effect of long-term treatment with an inhaled corticosteroid on airway hyperresponsiveness and clinical asthma in non-steroid dependent asthmatics. Am Rev Respir Dis 1990; 142: 832–6

    PubMed  CAS  Google Scholar 

  33. Glass M, Snader LA. Effect of the inhaled LTD4-receptor antagonist, ICI 204,219, on cold-air-induced bronchoconstriction in patients with asthma [abstract]. J Allergy Clin Immunol 1994; 93: 295

    Google Scholar 

  34. Spector SL. Update on exercise-induced asthma. Ann Allergy 1993; 71: 571–7

    PubMed  CAS  Google Scholar 

  35. Finnerty JP, Wood-Baker R, Thomson H, et al. Role of leukotrienes in exercise-induced asthma. Inhibitory effect of ICI-204-219, a potent leukotriene D4 antagonist. Am Rev Respir Dis 1992; 145: 746–9

    PubMed  CAS  Google Scholar 

  36. Makker HK, Lau LC, Thomson HW, et al. The protective effect of inhaled leukotriene D4 receptor antagonist ICI 204,219 against exercise-induced asthma. Am Rev Respir Dis 1993; 147: 1413–8

    PubMed  CAS  Google Scholar 

  37. Hui KP, Barnes NC. Lung function improvement in asthma with a cysteinyl-leukotriene receptor antagonist. Lancet 1991; 337: 1062–3

    Article  PubMed  CAS  Google Scholar 

  38. Kemp JP, Glass M, Minkwitz MC. Onset of action of the leukotriene-receptor antagonist, zafirlukast (Accolate™), in patients with asthma [abstract]. J Allergy Clin Immunol 1995; 95: 351

    Google Scholar 

  39. Spector SL, Glass M, Minkwitz M, et al. The effect of six weeks of therapy with oral doses of ICI 204,219 in asthmatics [abstract]. Am Rev Respir Dis 1992; 145: A16

    Google Scholar 

  40. Spector SL, Smith LJ, Glass M, et al. Effects of 6 weeks of therapy with oral doses of ICI 204,219, a leukotriene D4 receptor antagonist, in subjects with bronchial asthma. Am J Respir Crit Care Med 1994; 150: 618–23

    PubMed  CAS  Google Scholar 

  41. Howland WI, Segal A, Glass M, et al. 6-week therapy with the oral leukotriene-receptor antagonist, ICI 204, 219 in the treatment of asthma [abstract]. J Allergy Clin Immunol 1994; 93: 259

    Google Scholar 

  42. Spector S, Miller CJ, Glass M. 13-week dose-response study with Accolate™ (zafirlukast) in patients with mild-to-moderate asthma [abstract]. Am J Resp Crit Care Med 1995; 151: A379

    Google Scholar 

  43. Lockey RF, Lavins BJ, Snader L. Effects of 13 weeks of treatment with ICI 204, 219 (Accolate™) in patients with mild-to-moderate asthma [abstract]. J Allergy Clin Immunol 1995; 95: 350

    Article  Google Scholar 

  44. Holgate ST, Anderson KD, Rodgers EM. Comparison of ‘Accolate’ (zafirlukast) with sodium cromoglycate in mild to moderate asthmatic patients [abstract]. Allergy 1995; 50: 319–20

    Google Scholar 

  45. Nathan RA, Glass M, Snader L. Effects of 13 weeks of treatment with ICI 204,219 (‘Accolate’) or cromolyn sodium (“Intal”) in patients with mild to moderate asthma [abstract]. J Allergy Clin Immunol 1995; 95: 388

    Google Scholar 

  46. Kelloway JS, Wyatt RA, Adlis SA. Comparison of patients’ compliance with prescribed oral and inhaled asthma medications. Arch Intern Med 1994; 154: 1349–52

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Medicine, UCLA School of Medicine, 11620 Wilshire Blvd., Suite 200, Los Angeles, California, 90025, USA

    Sheldon L. Spector (Clinical Professor)

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Spector, S.L. Management of Asthma with Zafirlukast. Drugs 52 (Suppl 6), 36–46 (1996). https://doi.org/10.2165/00003495-199600526-00007

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