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Montelukast

A Review of its Therapeutic Potential in Persistent Asthma

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Summary

Abstract

Montelukast is a cysteinyl leukotriene receptor antagonist used to treat persistent asthma in patients aged ≥6 years.

The drug has a rapid onset of action. Improvements in lung function and reductions in as-needed β2-agonist usage are apparent within 1 day of initiating montelukast treatment in adults and adolescents (aged ≥15 years treated with 10 mg/day) or children (aged 6 to 14 years treated with 5 mg/day) with persistent asthma as shown in clinical trials.

In two 12-week, multicentre, randomised, double-blind studies in adults and adolescents aged ≥15 years with persistent asthma [forced expiratory volume in 1 second (FEV1) = 50 to 85% predicted] there was significantly (p ≤ 0.05) greater improvement in FEV1, symptom scores, peak expiratory flow (PEF), as-needed β2-agonist use, peripheral eosinophil counts and health-related quality of life (QOL) in patients treated with montelukast 10 mg/day than in recipients of placebo. Improvements were significantly greater in patients treated with inhaled beclomethasone 400 μg/day than in recipients of montelukast 10 mg/day in 1 of these studies. Nonetheless, 42% of montelukast recipients experienced ≥11% improvement in FEV1, the median improvement in this parameter in beclomethasone-treated patients.

In an 8-week multicentre, randomised, double-blind, study in children aged 6 to 14 years with persistent asthma (FEV1 50 to 85% predicted), montelukast 5 mg/day produced significantly greater improvements in FEV1, clinic PEF, as-needed β2-agonist use, peripheral eosinophil counts, asthma exacerbations and QOL scores than placebo.

The combination of montelukast 10 mg/day plus inhaled beclomethasone 200μg twice daily provided significantly better asthma control than inhaled beclomethasone 200μg twice daily in adults with poorly controlled asthma (mean FEV1 = 72% predicted) despite 4 weeks treatment with inhaled beclomethasone. Patients receiving the combination experienced significant improvements in FEV1 and morning PEF, significant reductions in daytime symptom scores, as-needed β2 agonist usage and night-time awakenings with asthma, and had significantly lower peripheral blood eosinophil counts after 16 weeks in this multicentre, randomised, double-blind, placebo-controlled study.

Among adults (FEV1 ≥70%) treated with montelukast 10 mg/day for 12 weeks, inhaled corticosteroid dosages were titrated downward by 47% (vs 30% in placebo recipients), 40% of patients were tapered off of inhaled corticosteroids (vs 29%), and significantly fewer patients (16 vs 30%) experienced failed corticosteroid rescues in a multicentre, randomised, double-blind study.

During clinical studies, the frequency of adverse events in montelukast-treated adults, adolescents and children was similar to that in placebo recipients.

In conclusion, montelukast is well tolerated and effective in adults and children aged ≥6 years with persistent asthma including those with exercise-induced bronchoconstriction and/or aspirin sensitivity. Furthermore, montelukast has glucocorticoid sparing properties. Hence, montelukast, as monotherapy in patients with mild persistent asthma, or as an adjunct to inhaled corticosteroids is useful across a broad spectrum of patients with persistent asthma.

Pharmacodynamic Properties

Cysteinyl leukotrienes [leukotriene C4 (LTC4), D4 (LTD4) and E4 (LTE4)] are important pro-inflammatory mediators in asthma. Montelukast is a competitive antagonist of these substances at the cysteinyl leukotriene type 1 (cysLT1) receptor. The affinity of montelukast (50% inhibitory concentration = ≥2.3 nmol/L) for the cloned human cysLT1 receptor was 2.5 to 5-fold lower than that of LTD4 and was generally similar to that of other commercially available cysLT1 receptor antagonists.

Montelukast 5 mg/day for ≥2 weeks reduced nitric oxide levels in exhaled air, a marker of inflammation, by ≥20% in children with mild asthma.

Peripheral blood eosinophil levels were significantly reduced from baseline in adult and paediatric patients treated with clinically relevant dosages of montelukast for ≥4 weeks.

Over a broad dose range (5 to 250mg), and at both peak and trough plasma concentrations, montelukast inhibited acute LTD4-induced bronchoconstriction in patients with asthma. Moreover, the onset of the antagonist effect of montelukast was readily apparent after absorption of a single dose.

Significant improvements in FEV1 were noted within 15 minutes of administration of montelukast 7mg intravenously.

Single oral doses of montelukast 100 or 250mg produced significant improvements in forced expiratory volume in 1 second (FEV1) within 1 hour of drug administration in patients with asthma including those receiving ongoing inhaled corticosteroids. Importantly, these improvements did not preclude a bronchodilator response to inhaled salbutamol (albuterol).

After 2 doses, montelukast 10 mg/day provided a significant protective effect against both early (EAR) and late asthmatic responses (LAR) in patients with mild asthma (FEV1 = 79 to 109% predicted) after allergen challenge in a double-blind, placebo-controlled, crossover study.

Montelukast reduced the deterioration in lung function after a standard exercise challenge (6-minute treadmill test) in patients with persistent asthma and exercise-induced bronchoconstriction treated for 8 or 12 weeks in well-designed trials. There was no evidence of tolerance to the protective effects of montelukast 10 mg/day, which were apparent within 3 days, in patients with exercise-induced bronchoconstriction. However, in patients treated with inhaled salmeterol 42μg twice daily, tolerance became apparent after an initial favourable response.

The frequency of as-needed β2-agonist usage after exercise challenge was significantly lower among patients treated with montelukast than placebo or salmeterol.

In children aged 6 to 14 years with exercise-induced bronchoconstriction, montelukast 5 mg/day for 2 days had similar protective effects to those achieved to those achieved in adults with 10 mg/day.

Pharmacokinetic Properties

After oral administration, approximately 64% of a 10mg dose of montelukast is absorbed, and maximum plasma concentrations are achieved within 3 to 4 hours. Steady state plasma concentrations are achieved on the second day of administration in volunteers. Montelukast is eliminated primarily by biliary excretion and hepatic oxidative metabolism. Oxidative metabolism of montelukast was attributed to cytochrome P450 isozymes (CYP3A4 and CYP2C9).

The pharmacokinetics of oral montelukast 10mg were generally similar in elderly volunteers (aged ≥65 years) and younger adults (aged 20 to 45 years).

In children aged 6 to 14 years, a 5mg dose administered as a chewable tablet provided similar systemic exposure to that obtained in adults after a 10mg dose.

Montelukast appears to have a low potential for drug-drug interactions. No pharmacokinetic drug-drug interactions were evident in patients receiving clinically significant doses of montelukast (10 mg/day) and warfarin, digoxin, terfenadine, fexofenadine, combined oral contraceptives, theophylline, prednisone or prednisolone.

Phenobarbital appeared to increase the metabolism of montelukast; however, dosage adjustments are not warranted in patients receiving this combination.

Therapeutic Potential in Patients With Persistent Asthma

Montelukast has been evaluated in randomised, placebo-controlled studies in adults, adolescents and children with persistent asthma. The drug was administered in the evening in all clinical trials.

In multicentre randomised, double-blind, placebo-controlled trials of 8 or 12 weeks’ duration in adults (aged ≥15 years) or children (aged 5 to 14 years) montelukast had a rapid onset of action (i.e. within 1 day).

In Adults

Adult patients with persistent asthma (FEV1 = 50 to 85% predicted) received montelukast 10 mg/day or placebo (n = 681) in 1 study, and montelukast 10 mg/day, inhaled beclomethasone 400 μg/day or placebo in another trial (n = 895). After 12 weeks of treatment in both studies, significant improvements in all outcome variables (FEV1, daytime symptom scores, morning and evening peak expiratory flow rate (PEF), frequency of as-needed β2-agonist usage, frequency of nocturnal awakenings, health-related quality of life scores and peripheral eosinophil counts) were obtained in montelukast- or inhaled beclomethasone-treated patients, but not in recipients of placebo. Improvements with inhaled beclomethasone were significantly greater than with montelukast. Recipients of montelukast or inhaled beclomethasone experienced significantly more asthma control days and significantly fewer asthma exacerbation days than placebo recipients in these trials.

The combination of montelukast 10 mg/day plus inhaled beclomethasone 200μg twice daily provided significantly better asthma control than inhaled beclomethasone 200μg twice daily in patients with poorly controlled asthma (mean FEV1 = 72% predicted, n = 642) despite 4 weeks treatment with inhaled beclomethasone. Patients were randomised to 1 of 4 double-blind treatments (montelukast 10mg daily plus inhaled placebo, inhaled beclomethasone 200μgtwice daily plus oral placebo, montelukast plus beclomethasone, or oral and inhaled placebos) in the study. When compared with patients continuing on inhaled beclomethasone alone, patients receiving the combination experienced significant improvements in FEV1 and morning PEF, significant reductions in daytime symptom scores, as-needed β2 agonist usage and night-time awakenings with asthma, and had significantly lower peripheral blood eosinophil counts after 16 weeks. Asthma control generally deteriorated in patients assigned to placebo and the frequency of discontinuation from the study because of worsening asthma was 15, 11.4, 4 and 1%, respectively, among patients who received placebo, montelukast, inhaled beclomethasone or the 2 drugs combined. These findings indicate that montelukast is not suitable for monotherapy in patients with moderate or severe persistent asthma.

Montelukast 10 mg/day allowed for significant reductions in inhaled cortico-steroid dosages in patients with persistent asthma receiving ongoing treatment with inhaled corticosteroids. Between the start of treatment and the end of a randomised, double-blind, 12-week study, the mean daily dosage of inhaled corticosteroid was decreased by 47 and 30% in patients treated with montelukast or placebo, respectively. A higher proportion of montelukast (40%) than placebo recipients (29%) were successfully tapered off of inhaled corticosteroids and significantly fewer patients discontinued montelukast than placebo because of failed corticosteroid rescues (16 vs 30%).

Montelukast 10 mg/day plus loratadine 20 mg/day produced significantly greater improvements in FEV1, symptom scores and β2-agonist use than montelukast plus placebo in a 2-week, randomised, crossover study in patients with mild to severe persistent asthma.

Meta-analysis of data from 4 multicentre, placebo-controlled trials demonstrated that there was no apparent differences in the magnitude of improvement in clinical end-points between patients with or without a history of allergic rhinitis after treatment with montelukast 10 mg/day.

In aspirin-sensitive adults with persistent asthma, 4 weeks’ treatment with montelukast 10 mg/day produced significant improvements in most outcome measures (i.e. FEV1, morning PEF, β2-agonist usage and nocturnal, but not daytime symptom scores) compared with placebo.

In Children

In paediatric patients aged 6 to 14 years, montelukast 5 mg/day for 8 weeks produced significant improvements in FEV1, the primary outcome variable, in a multicentre, randomised, double-blind study. Significant improvement was also obtained in many (frequency of as-needed β2-agonist use, clinic PEF, Paediatric AQLQ scores and peripheral eosinophil counts) but not all secondary outcome variables (daytime symptom scores, morning and evening PEF in patient diaries, nocturnal awakenings). Montelukast significantly reduced the frequency of days with asthma exacerbations and the proportion of patients with asthma exacerbations compared with placebo.

Among children randomised to further treatment with montelukast or inhaled beclomethasone at the end of this study the mean change from baseline in FEV1 was similar (6.47 and 6.39%) after 1.4 years of follow-up.

Four weeks of treatment with montelukast 5 mg/day was compared with inhaled sodium cromoglycate 1.6 mg four times daily in 2 randomised, crossover studies in children aged 6 to 11 years with persistent asthma. Withdrawal rates were greater during treatment with sodium cromoglycate than montelukast. ≥86% of parents and ≥79% of patients expressed a preference for montelukast. In 1 of these studies, in which adherence with inhaled sodium cromoglycate was poor compared with montelukast (45 vs 82%, respectively), as-needed β2-agonist usage was significantly lower during treatment with montelukast.

Tolerability

During clinical trials in adults or children with persistent asthma the frequencyof adverse events in montelukast-treated patients was similar to that in placebo recipients. Headache was the most frequent adverse event, reported by 18.4 and 18.1% of adult recipients of montelukast and placebo, respectively.

In paediatric patients treated for 8 weeks, diarrhoea, laryngitis, pharyngitis, nausea, otitis, sinusitis and viral infections occurred in more than 2% of patients treated with montelukast and were more prevalent in recipients of montelukast 5 mg/day than placebo.

Churg-Strauss syndrome has been reported rarely in adult patients during treatment with montelukast; however, it is unlikely that there is a causal relationship between the drug and the emergence of this condition.

Dosage and Administration

Montelukast is indicated for the treatment of persistent asthma in patients aged ≥6 years. The recommended dosage of montelukast is 10 mg/day in adults and adolescents aged ≥15 years and 5 mg/day in children aged 6 to 14 years. The drug is administered in the evening with or without food. Dosage adjustments are not required in elderly patients or in those with renal or mild to moderate hepatic dysfunction.

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Notes

  1. The maximum LTD4 concentration tested was approximately 100-fold greater than the mean of 2 baseline PC50 values.

  2. In accord with US labelling requirements, the dose of salmeterol was reported as the amount delivered through the mouthpiece (42μg) rather than the amount delivered per actuation (50μg).

  3. The dosage of sodium cromoglycate was reported as 1.6[125] and 2mg[126] 4 times daily in these studies. The differences in reported dosages reflect labelling requirements in the US where the proportion of the dose delivered through the mouthpiece (1.6mg) is used and elsewhere, where the amount actuated (2mg) is used.

References

  1. Sheffer AL, Bartal M, Bousquet J, et al. Global initiative for asthma. Global strategy for asthma management and prevention [on line]. [Accessed 22 Mar, 2000] NHLBI/WHO workshop report. National Institutes of Health. National Heart, Lung and Blood Institute. 1995 Mar; Publication No. 95-3659. Available at http://www.ginasthma.com

  2. National Asthma Education and Prevention Program. Expert Panel Report II: Guidelines for the diagnosis and management of asthma [on line]. [Accessed 2 Jul, 1999] Bethesda: National Institutes of Health, National Heart Lung and Blood Institute. 1997 Jul; Publication no. 97-4051. Available at: http://www.nhbli.nih.gov.pdf

  3. British Thoracic Society, National Asthma Campaign, Royal College of Physicians of London, et al. The British guidelines on asthma management 1995 review and position statement. Thorax 1997 Feb; 52 Suppl. 1: S1–21

    Article  Google Scholar 

  4. Malmstrom K, Meltzer E, Prenner B, et al. Effects of montelukast (a leukotriene receptor antagonist), loratadine, montelukast + loratadine and placebo in seasonal allergic rhinitis and conjunctivitis [abstract]. J Allergy Clin Immunol 1998 Jan; 101 (Pt 2): S97

    Google Scholar 

  5. Sheftell FD, Rapoport AM, Walker B, et al. Leukotriene (LK) antagonists in the prophylaxis of migraine: a potential role for a new class of agents [abstract]. Headache 1999 May; 39(5): 381

    Google Scholar 

  6. Markham A, Faulds D. Montelukast. Drugs 1998 Aug; 56: 251–6

    Article  PubMed  CAS  Google Scholar 

  7. Drazen JM, Israel E, O’Byrne PM. Treatment of asthma with drugs modifying the leukotriene pathway. N Engl J Med 1999 Jan 21; 340: 197–206

    Article  PubMed  CAS  Google Scholar 

  8. Crooks SW, Stockley RA. Leukotriene B4. International Journal of Biochemistry and Cell Biology 1998; 30: 173–8

    Article  PubMed  CAS  Google Scholar 

  9. Peters-Golden M, Brock TG. Intracellular compartmentalization of leukotriene biosynthesis. Am J Respir Crit Care Med 2000; 161 Suppl.: S36–40

    PubMed  CAS  Google Scholar 

  10. Samuelsson B. The discovery of the leukotrienes. Am J Respir Crit Care Med 2000; 161 Suppl.: S2–6

    PubMed  CAS  Google Scholar 

  11. Dahlén S-E. Pharmacological characterization of leukotriene receptors. Am J Respir Crit Care Med 2000; 161 Suppl.: S41–5

    PubMed  Google Scholar 

  12. Busse W. The role and contribution of leukotrienes in asthma. Ann Allergy Asthma Immunol 1998 Jul; 81: 17–29

    Article  PubMed  CAS  Google Scholar 

  13. Rodger IW. Leukotrienes, asthma, and the preclinical science of montelukast. Eur Resp Rev 1998 Sep; 8: 358–60

    Google Scholar 

  14. Howarth PH. ABC of allergies: pathogenic mechanisms: a rational basis for treatment. BMJ 1998 Mar 7; 316: 758–61

    Article  PubMed  CAS  Google Scholar 

  15. O’Byrne PM, Israel E, Drazen JM. Antileukotrienes in the treatment of asthma. Ann Intern Med 1997 Sep 15; 127: 472–80

    PubMed  Google Scholar 

  16. Rachelefsky G. Childhood asthma and allergic rhinitis: the role of leukotrienes. J Pediatr 1997; 131(3): 348–55

    Article  PubMed  CAS  Google Scholar 

  17. Leff JA. Leukotriene modifiers as novel therapeutics in asthma. Clin Exp Allergy 1998 Nov; 28 Suppl. 5: 147–53

    Article  PubMed  CAS  Google Scholar 

  18. Lazarus SC. Inflammation, inflammatory mediators, and mediator antagonists in asthma. J Clin Pharmacol 1998; 38: 577–82

    PubMed  CAS  Google Scholar 

  19. Claesson H-E, Dahlén S-E. Asthma and leukotrienes: anti-leukotrienes as novel anti-asthmatic drugs. J Intern Med 1999; 245: 205–27

    Article  PubMed  CAS  Google Scholar 

  20. Wenzel SE. Inflammation, leukotrienes and the pathogenesis of the late asthmatic response [editorial]. Clin Exp Allergy 1999; 29: 1–3

    Article  PubMed  CAS  Google Scholar 

  21. Devillier P, Baccard N, Advenier C. Leukotrienes, leukotriene receptor antagonists and leukotriene synthesis inhibitors in asthma: an update. Part II: clinical studies with leukotriene receptor antagonists and leukotriene synthesis inhibitors in asthma. Pharmacol Res 1999; 40(1): 15–29

    CAS  Google Scholar 

  22. Devillier P, Baccard N, Advenier C. Leukotrienes, leukotriene receptor antagonists and leukotriene synthesis inhibitors in asthma: an update. Part I: synthesis, receptors and role of leukotrienes in asthma. Pharmacol Res 1999; 40(1): 3–13

    CAS  Google Scholar 

  23. Drazen JM. Leukotrienes as mediators of airway obstruction. Am J Respir Crit Care Med 1998; 158: S193–200

    PubMed  CAS  Google Scholar 

  24. Holgate ST, Sampson AP. Antileukotriene therapy: future directions. Am J Respir Crit Care Med 2000; 161 Suppl.: S147–53

    PubMed  CAS  Google Scholar 

  25. Leff AR. Role of leukotrienes in bronchial hyperresponsiveness and cellular responses in airways. Am J Respir Crit Care Med 2000; 161 Suppl.: S125–32

    PubMed  CAS  Google Scholar 

  26. Calhoun WJ, Lavins BJ, Minkwitz MC, et al. Effect of zafirlukast (Accolate) on cellular mediators of inflammation. Am J Respir Crit Care Med 1998; 157: 1381–9

    PubMed  CAS  Google Scholar 

  27. Pavord ID, Ward R, Woltmann G, et al. Induced sputum eicosanoid concentrations in asthma. Am J Respir Crit Care Med 1999; 160: 1905–9

    PubMed  CAS  Google Scholar 

  28. Tagari P, Rasmussen JB, Delorme D, et al. Comparison of urinary leukotriene E4 and 16-carboxytetranordihydro leukotriene E4 excretion in allergic asthmatics after inhaled antigen. Eicosanoids 1990; 3: 75–80

    PubMed  CAS  Google Scholar 

  29. Dworski R, Sheller JR. Urinary mediators and asthma [editorial]. Clin Exp Allergy 1998; 28: 1309–12

    Article  PubMed  CAS  Google Scholar 

  30. O’Sullivan S, Roquet A, Dahlén B, et al. Urinary excretion of inflammatory mediators during allergen-induced early and late phase asthmatic reactions. Clin Exp Allergy 1998; 28: 1332–9

    Article  PubMed  Google Scholar 

  31. Kumlin M. Measurements of leukotrienes in the urine: strategies and applications. Allergy 1997; 52: 124–35

    Article  PubMed  CAS  Google Scholar 

  32. Dahlén SE, Kumlin M. Can asthma be studied in urine? [editorial]. Clin Exp Allergy 1998; 28: 129–33

    Article  PubMed  Google Scholar 

  33. Drazen JM, Austen KF. Leukotrienes and airway responses. Am Rev Respir Dis 1987; 136: 985–98

    Article  PubMed  CAS  Google Scholar 

  34. Barnes NC, Piper PJ, Costello JF. Comparative effects of inhaled leukotriene C4, leukotriene D4, and histamine in normal human subjects. Thorax 1984; 39: 500–4

    Article  PubMed  CAS  Google Scholar 

  35. Ellis JL, Undem BJ. Role of cysteinyl-leukotrienes and histamine in mediating intrinsic tone in isolated human bronchi. Am J Respir Crit Care Med 1994; 149: 118–22

    PubMed  CAS  Google Scholar 

  36. Watson N, Magnussen H, Rabe KF. Inherent tone of human bronchus: role of eicosanoids and the epithelium. Br J Pharmacol 1997; 121: 1099–104

    Article  PubMed  CAS  Google Scholar 

  37. O’Byrne PM. Leukotriene bronchoconstriction induced by allergen and exercise. Am J Respir Crit Care Med 2000; 161 Suppl.: S68–72

    PubMed  Google Scholar 

  38. Foster A, Chan CC. Peptide leukotriene involvement in pulmonary eosinophil migration upon antigen challenge in the actively sensitized guinea pig. Int Arch Allergy Appl Immunol 1991; 96(3): 279–84

    Article  PubMed  CAS  Google Scholar 

  39. Underwood DC, Osborn RR, Newsholme SJ, et al. Persistent airway eosinophilia after leukotriene (LT) D4 administration in the guinea pig. Am J Respir Crit Care Med 1996; 154: 850–7

    PubMed  CAS  Google Scholar 

  40. Laitinen LA, Laitinen A, Haahtela T, et al. Leukotriene E4 and granulocytic infiltration into asthmatic airways. Lancet 1993 Apr 17; 341: 989–90

    Article  PubMed  CAS  Google Scholar 

  41. Diamant Z, Hiltermann JT, van Rensen EL, et al. The effect of inhaled leukotriene D4 and methacholine on sputum cell differentials in asthma. Am J Respir Crit Care Med 1997; 155: 1247–53

    PubMed  CAS  Google Scholar 

  42. Mulder A, Gauvreau GM, Watson RM, et al. Effect of inhaled leukotriene D4 on airway eosinophilia and airway hyperresponsiveness in asthmatic subjects. Am J Respir Crit Care Med 1999; 159: 1562–7

    PubMed  CAS  Google Scholar 

  43. Hisada T, Salmon M, Nasuhara Y, et al. Cysteinyl-leukotrienes partly mediate eotaxin-induced bronchial hyperresponsiveness and eosinophilia in IL-5 transgenic mice. Am J Respir Crit Care Med 1999 Aug; 160(2): 571–5

    PubMed  CAS  Google Scholar 

  44. Weersink EJM, Postma DS, Aalbers R, et al. Early and late asthmatic reaction after allergen challenge. Respir Med 1994; 88: 103–14

    Article  PubMed  CAS  Google Scholar 

  45. Diamant Z, Grootendorst DC, Veselic-Charvat M, et al. The effect of montelukast (MK-0476), a cysteinyl leukotriene receptor antagonist, on allergen-induced airway responses and sputum cell counts in asthma. Clin Exp Allergy 1999 Jan; 29(1): 42–51

    Article  PubMed  CAS  Google Scholar 

  46. Roquet A, Dahlén B, Kumlin M, et al. Combined antagonism of leukotrienes and histamine produces predominant inhibition of allergen-induced early and late phase airway obstruction in asthmatics. Am J Respir Crit Care Med 1997; 155: 1856–63

    PubMed  CAS  Google Scholar 

  47. Hamilton A, Faiferman I, Stober P, et al. Pranlukast, a cysteinyl leukotriene receptor antagonist, attenuates allergen-induced early- and late-phase bronchoconstriction and airway hyperresponsiveness in asthmatic subjects. J Allergy Clin Immunol 1998; 102: 177–83

    Article  PubMed  CAS  Google Scholar 

  48. Szczeklik A, Stevenson DD. Aspirin-induced asthma: advances in pathogenesis and management. J Allergy Clin Immunol 1999 Jul; 104(1): 5–13

    Article  PubMed  CAS  Google Scholar 

  49. Cowburn AS, Sladek K, Soja J, et al. Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma. J Clin Invest 1998; 101: 834–46

    Article  PubMed  CAS  Google Scholar 

  50. Sanak M, Simon H-U, Szczeklik A. Leukotriene C4 synthase promoter polymorphism and risk of aspirin-induced asthma. Lancet 1997 Nov 29; 350: 1599–600

    Article  PubMed  CAS  Google Scholar 

  51. Holgate ST. Genetic and environmental interaction in allergy and asthma. J Allergy Clin Immunol 1999 Dec; 104(6): 1139–46

    Article  PubMed  CAS  Google Scholar 

  52. Szczeklik A, Sanak M. Genetic mechanisms in aspirin-induced asthma. Am J Respir Crit Care Med 2000; 161 Suppl.: S142–6

    PubMed  CAS  Google Scholar 

  53. Yoshida S, Sakamoto H, Ishizaki Y, et al. Efficacy of leukotriene receptor antagonist in bronchial hyperresponsiveness and hypersensitivity to analgesic in aspirin-intolerant asthma. Clin Exp Allergy 2000; 30: 64–70

    Article  PubMed  CAS  Google Scholar 

  54. Daffern PJ, Muilenburg D, Hugli TE, et al. Association of urinary leukotriene E4 excretion during aspirin challenges with severity of respiratory responses. J Allergy Clin Immunol 1999 Sep; 104 (3 Pt 1): 559–64

    Article  PubMed  CAS  Google Scholar 

  55. Dahlén B. Treatment of aspirin-intolerant asthma with anti-leukotrienes. Am J Respir Crit Care Med 2000; 161 Suppl.: S137–41

    PubMed  Google Scholar 

  56. Szczeklik A. Mechanism of aspirin-induced asthma. Allergy 1997 Jun; 52(6): 613–9

    Article  PubMed  CAS  Google Scholar 

  57. Dahlén B, Margolskee DJ, Zetterstrom O, et al. Effect of the leukotriene receptor antagonist MK-069 on baseline pulmonary function in aspirin sensitive asthmatic subjects. Thorax 1993; 48: 1205–10

    Article  PubMed  Google Scholar 

  58. Dahlén B, Nizankowska E, Szczeklik A, et al. Benefits from adding the 5-lipoxygenase inhibitor zileuton to conventional therapy in aspirin-intolerant asthmatics. Am J Respir Crit Care Med 1998; 157: 1187–94

    PubMed  Google Scholar 

  59. Lynch KR, O’Neill GP, Liu Q, et al. Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature 1999 Jun 24; 399: 789–93

    Article  PubMed  CAS  Google Scholar 

  60. Chan CC, Ecclestone P, Nicholson DW, et al. Leukotriene D4-induced increases in cytosolic calcium in THP-1 cells: dependence on extracellular calcium and inhibition with selective leukotriene D4 receptor antagonists. J Pharmacol Exp Ther 1994 Jun; 269(3): 891–6

    PubMed  CAS  Google Scholar 

  61. Metters KM, Zamboni RJ. Photoaffinity labeling of the leukotriene D4 receptor in guinea pig lung. J Biol Chem 1993 Mar 25; 268(9): 6487–95

    PubMed  CAS  Google Scholar 

  62. Hoshino M, Izumi T, Shimizu T. Leukotriene D4 activates mitogen-activated protein kinase through a protein kinase Cα-Raf-1-dependent pathway in human monocytic leukemia THP-1 cells. J Biol Chem 1998 Feb 27; 273(9): 4878–82

    Article  PubMed  CAS  Google Scholar 

  63. Jones TR, Labelle M, Belley M, et al. Pharmacology of montelukast sodium (Singulair), a potent and selective leukotriene D4 receptor antagonist [published erratum appears in Can J Physiol Pharmacol 1995 Jun; 73(6): 747]. Can J Physiol Pharmacol 1995 Feb; 73: 191–201

    Article  PubMed  CAS  Google Scholar 

  64. Labelle M, Belley M, Gareau Y, et al. Discovery of MK-0476, a potent and orally active leukotriene D4 receptor antagonist devoid of peroxisomal enzyme induction. Bioorg Med Chem Lett 1995; 5(3): 283–8

    Article  CAS  Google Scholar 

  65. Guay D, Gauthier JY, Dufresne C, et al. A series of non-quinoline cysLT1 receptor antagonists: SAR study on pyridyl analogs of Singulair. Bioorg Med Chem Lett 1998; 8: 453–8

    Article  PubMed  CAS  Google Scholar 

  66. Arakida Y, Suwa K, Ohga K, et al. In vitro pharmacologic profile of YM158, a new dual antagonist for LTD4 and TXA2 receptors. J Pharmacol Exp Ther 1998 Nov; 287: 633–9

    PubMed  CAS  Google Scholar 

  67. Ihaku D, Cameron L, Suzuki M, et al. Montelukast, a leukotriene receptor antagonist, inhibits the late airway response to antigen, airway eosinophilia, and IL-5-expressing cells in Brown Norway rats. J Allergy Clin Immunol 1999 Dec; 104(6): 1147–54

    Article  PubMed  CAS  Google Scholar 

  68. Therattil J, Wang YC, Than S, et al. In vitro effects of montelukast on levels of IL-5 mRNA and cysteinyl leukotrienes (CysLT) in allergen-stimulated peripheral blood mononu-clear cells (PBMC) from patients with asthma [abstract]. Ann Allergy Asthma Immunol 1999 Jan; 82: 80

    Google Scholar 

  69. Volovitz B, Tabachnik E, Nussinovitch M, et al. Montelukast, a leukotriene receptor antagonist, reduces the concentration of leukotrienes in the respiratory tract of children with persistent asthma. J Allergy Clin Immunol 1999 Dec; 104(6): 1162–7

    Article  PubMed  CAS  Google Scholar 

  70. Bisgaard H, Loland L, Anhøj J. NO in exhaled air of asthmatic children is reduced by the leukotriene receptor antagonist montelukast. Am J Respir Crit Care Med 1999; 160: 1227–31

    PubMed  CAS  Google Scholar 

  71. Bratton DL, Lanz MJ, Miyazawa N, et al. Exhaled nitric oxide before and after montelukast sodium therapy in school-age children with chronic asthma: a preliminary study. Pediatr Pulmonol 1999 Dec; 28(6): 402–7

    Article  PubMed  CAS  Google Scholar 

  72. Ramsay C, Li D, Wang T, et al. Bronchial biopsy specimen variability: requirement for large sample size and repeat measurements to improve reliability [abstract]. Am J Respir Crit Care Med 1999; 159(3): A655

    Google Scholar 

  73. Pizzichini E, Leff JA, Reiss TF, et al. Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial. Eur Respir J 1999; 14: 12–8

    Article  PubMed  CAS  Google Scholar 

  74. Sue-Chu M, Sandsund M, Reinertsen R, et al. Montelukast does not have any ergogenic effects in non-asthmatic elite athletes [abstract]. Am J Respir Crit Care Med 1999 Mar; 159 (3 Pt 2): A640

    Google Scholar 

  75. Barnes PJ, Chung KF, Page CP. Inflammatory mediators of asthma: an update. Pharmacol Rev 1998; 50 (4 515-596)

  76. Jatakanon A, Lim S, Kharitonov SA, et al. Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. Thorax 1998; 53: 91–5

    Article  PubMed  CAS  Google Scholar 

  77. Reiss TF, Chervinsky P, Dockhorn RJ, et al. Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of chronic asthma: a multicenter, randomized, double-blind trial. Arch Intern Med 1998 Jun 8; 158: 1213–20

    Article  PubMed  CAS  Google Scholar 

  78. Malmstrom K, Rodriguez-Gomez G, Guerra J, et al. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma: a randomized, controlled trial. Ann Intern Med 1999 Mar 16; 130: 487–95

    PubMed  CAS  Google Scholar 

  79. Knorr B, Matz J, Bernstein JA, et al. Montelukast for chronic asthma in 6- to 14-year-old children: a randomized double-blind trial. JAMA 1998 Apr 15; 279(15): 1181–6

    Article  PubMed  CAS  Google Scholar 

  80. Laviolette M, Malmstrom K, Lu S, et al. Montelukast added to inhaled beclomethasone in treatment of asthma. Am J Respir Crit Care Med 1999; 160: 1862–8

    PubMed  CAS  Google Scholar 

  81. Nakamura H, Weiss ST, Israel E, et al. Eotaxin and impaired lung function in asthma. Am J Respir Crit Care Med 1999; 160: 1952–6

    PubMed  CAS  Google Scholar 

  82. Pizzichini E, Pizzichini MMM, Efthimiadis A, et al. Measuring airway inflammation in asthma: eosinophils and eosinophilic cationic protein in induced sputum compared with peripheral blood. J Allergy Clin Immunol 1997; 99: 539–44

    Article  PubMed  CAS  Google Scholar 

  83. Horn BR, Robin ED, Theodore J, et al. Total eosinophil counts in the management of bronchial asthma. N Engl J Med 1975 May 29; 1975(22): 1152–5

    Article  Google Scholar 

  84. De Lepeleire I, Reiss TF, Rochette F, et al. Montelukast causes prolonged, potent leukotriene D4-receptor antagonism in the airways of patients with asthma. Clin Pharmacol Ther 1997 Jan; 61: 83–92

    Article  PubMed  Google Scholar 

  85. Paterson MC, Wilson AM, Dempsey OJ, et al. The effect of combination therapy with salmeterol and montelukast in asthmatic patients receiving inhaled corticosteroids (abstracts-on-disk). Annual Congress European Respiratory Society, Madrid Spain, 9–13 Oct. 1999 Abstract P3490

  86. Leff JA, Busse WW, Pearlman D, et al. Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction [see comments]. N Engl J Med 1998 Jul 16; 339: 147–52

    Article  PubMed  CAS  Google Scholar 

  87. Reiss TF, Sorkness CA, Stricker W, et al. Effects of montelukast (MK-0476); a potent cysteinyl leukotriene receptor antagonist, on bronchodilation in asthmatic subjects treated with and without inhaled corticosteroids. Thorax 1997 Jan; 52: 45–8

    Article  PubMed  CAS  Google Scholar 

  88. Dockhorn RJ, Baumgartner RA, Leff JA, et al. Comparison of the effects of intravenous and oral montelukast on airway function: a double blind, placebo controlled, three period, crossover study in asthmatic patients. Thorax 2000; 55: 260–5

    Article  PubMed  CAS  Google Scholar 

  89. Kuitert LM, Barnes NC. Leukotriene receptor antagonists: useful in acute asthma? [editorial]. Thorax 2000; 55: 255–6

    Article  PubMed  CAS  Google Scholar 

  90. Bronsky EA, Kemp JP, Zhang J, et al. Dose-related protection of exercise bronchoconstriction by montelukast, a cysteinyl leukotriene-receptor antagonist, at the end of a once-daily dosing interval. Clin Pharmacol Ther 1997 Nov; 62: 556–61

    Article  PubMed  CAS  Google Scholar 

  91. Reiss TF, Hill JB, Harman E, et al. Increased urinary excretion of LTE4 after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist. Thorax 1997 Dec; 52: 1030–5

    Article  PubMed  CAS  Google Scholar 

  92. Villaran C, O’Neill SJ, Helbling A, et al. Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction. J Allergy Clin Immunol 1999 Sep; 104 (3 Pt 1): 547–53

    Article  PubMed  CAS  Google Scholar 

  93. Edelman JM, Turpin JA, Bronsky EA, et al. Oral montelukast compared with inhaled salmeterol to prevent exercise-induced bronchoconstriction: a randomized, double-blind trial. Ann Intern Med 2000 Jan 18; 132(2): 97–104

    PubMed  CAS  Google Scholar 

  94. Turpin JA, Edelman JM, DeLucca PT, et al. Chronic administration of montelukast (MK-476) is superior to inhaled salmeterol in the prevention of exercise-induced bronchoconstriction (EIB) [abstract]. Am J Respir Crit Care Med 1998 Mar; 157 (Pt 2 Suppl.): A456

    Google Scholar 

  95. Meltzer SS, Hasday JD, Cohn J, et al. Inhibition of exercise-induced bronchospasm by zileuton: a 5-lipoxygenase inhibitor. Am J Respir Crit Care Med 1996 Mar; 153(3): 931–5

    PubMed  CAS  Google Scholar 

  96. Dessanges J-F, Préfaut C, Taytard A, et al. The effect of zafirlukast on repetitive exercise-induced bronchoconstriction: the possible role of leukotrienes in exercise-induced refractoriness. J Allergy Clin Immunol 1999 Dec; 104(6): 1155–61

    Article  PubMed  CAS  Google Scholar 

  97. Hansen-Flaschen J, Schotland H. New treatments for exercise-induced asthma. N Engl J Med 1998 Jul 16; 339: 192–3

    Article  PubMed  CAS  Google Scholar 

  98. Ramage L, Lipworth BJ, Ingram CG, et al. Reduced protection against exercise induced bronchoconstriction after chronic dosing with salmeterol. Respir Med 1994; 88: 363–8

    Article  PubMed  CAS  Google Scholar 

  99. Nelson JA, Strauss L, Skowronski M, et al. Effect of long-term salmeterol treatment on exercise-induced asthma. N Engl J Med 1998; 339: 141–6

    Article  PubMed  CAS  Google Scholar 

  100. Simons FER, Gerstner TV, Cheang MS. Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment. Pediatrics 1997 May; 99(5): 655–9

    Article  PubMed  CAS  Google Scholar 

  101. Reiss TF. Exercise-induced asthma [letter]. N Engl J Med 1998 Dec 10; 339: 1785

    Google Scholar 

  102. Kemp JP, Dockhorn RJ, Shapiro GG, et al. Montelukast once daily inhibits exercise-induced bronchoconstriction in 6-to 14-year-old children with asthma. J Pediatr 1998 Sep; 133: 424–8

    Article  PubMed  CAS  Google Scholar 

  103. Pearlman DS, Ostrom NK, Bronsky EA, et al. The leukotriene D4-receptor antagonist zafirlukast attenuates exercise-induced bronchoconstriction in children. J Pediatr 1999 Mar; 134(3): 273–9

    Article  PubMed  CAS  Google Scholar 

  104. Merck and Co. Inc. Singulair (montelukast) prescribing information. Merck and Co. Inc. Rahway NJ USA. Feb 1998

  105. Zhao JJ, Rogers JD, Holland SD, et al. Pharmacokinetics and bioavailability of montelukast sodium (MK-0476) in healthy young and elderly volunteers. Biopharm Drug Dispos 1997 Dec; 18: 769–77

    Article  PubMed  CAS  Google Scholar 

  106. Balani SK, Xu X, Pratha V, et al. Metabolic profiles of montelukast sodium (Singulair), a potent cysteinyl leukotriene, receptor antagonist, in human plasma and bile. Drug Metab Dispos 1997 Nov; 25: 1282–7

    PubMed  CAS  Google Scholar 

  107. Chiba M, Xu X, Nishime JA. Hepatic microsomal metabolism of montelukast, a potent leukotriene D4 receptor antagonist, in humans. Drug Metab Dispos 1997 Sep; 25: 1022–31

    PubMed  CAS  Google Scholar 

  108. Liu L, Cheng H, Zhao JJ, et al. Determination of montelukast (MK-0476) and its S-enantiomer in human plasma by stereoselective high-performance liquid chromatography with column-switching. J Pharmaceutical and Biomedical Analysis 1997; 15: 631–8

    Article  CAS  Google Scholar 

  109. Knorr B, Larson P, Chervinsky P, et al. Selection of a montelukast dose in 6- to 14-year-olds by a comparison of pediatric and adult single-dose pharmacokinetic profiles [abstract]. Clin Pharmacol Ther 1998 Feb; 63: 191

    Google Scholar 

  110. Knorr B, Nguyen H, Villaran C, et al. Selection of a montelukast dose in 2- to 5-year-olds by a comparison of pediatric and adult single-dose population pharmacokinetic profiles [abstract]. Clin Pharmacol Ther 1998 Feb; 63: 191

    Google Scholar 

  111. Holland S, Shahane A, Rogers JD, et al. Metabolism of montelukast is increased by multiple doses of phenobarbital [abstract]. Clin Pharmacol Ther 1998 Feb; 63: 231

    Google Scholar 

  112. Malmstrom K, Schwartz J, Reiss TF, et al. Effect of montelukast on single-dose theophylline pharmacokinetics. Am J Ther 1998 May; 5: 189–95

    Article  PubMed  CAS  Google Scholar 

  113. Van Hecken A, Depre M, Verbesselt R, et al. Effect of montelukast on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers. J Clin Pharmacol 1999 May; 39(5): 495–500

    PubMed  Google Scholar 

  114. Depre M, Van Hecken A, Verbesselt R, et al. Effect of multiple doses of montelukast, a CysLT1 receptor antagonist, on digoxin pharmacokinetics in healthy volunteers. J Clin Pharmacol 1999 Sep; 39(9): 941–4

    Article  PubMed  CAS  Google Scholar 

  115. Holland S, Gertz B, DeSmet M, et al. Montelukast has no effect on terfenadine pharmacokinetics (PK) or QTc [abstract]. Clin Pharmacol Ther 1998 Feb; 63: 232

    Google Scholar 

  116. Schwartz J, Larson P, Ebel D, et al. Lack of impact of a leukotriene (LT) D4 receptor antagonist, montelukast (M), on ethinyl estradiol (EE) and norethindrone (NET) serum concentrations [abstract]. 98th Annual Meeting American Society for Clinical Pharmacology and Therapeutics, San Diego, CA, USA 1997 Mar 5: 162

    Google Scholar 

  117. Noonan MJ, Chervinsky P, Brandon M. Montelukast, a potent leukotriene receptor antagonist, causes dose-related improvements in chronic asthma. Eur Respir J 1998 Jun; 11: 1232–9

    Article  PubMed  CAS  Google Scholar 

  118. Altaian LC, Munk Z, Seltzer J, et al. A placebo-controlled, dose-ranging study of montelukast, a cysteinyl leukotriene-receptor antagonist. J Allergy Clin Immunol 1998 Jul; 102: 50–6

    Article  Google Scholar 

  119. Lu S, Reiss TF. The dose selection of montelukast sodium (MK-0476). Eur Resp Rev 1998 Sep; 8: 361–5

    Google Scholar 

  120. Skalky CS, Edelman JM, Polis A, et al. Montelukast sodium (MK) compared to inhaled beclomethasone dipropionate (BD) in adult asthmatics: a randomized clinical trial [abstract]. J Allergy Clin Immunol 1999 Jan; 103 (Pt 2): 228

    Google Scholar 

  121. Löfdahl C-G, Reiss TF, Leff JA, et al. Randomised, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients. BMJ 1999 July 10; 319: 87–90

    Article  PubMed  Google Scholar 

  122. Baumgartner RA, Polis A, Angner R, et al. Comparison between montelukast and inhaled beclomethasone therapy in chronic asthma: a double-blind, placebo-controlled, parallel study in asthmatic patients [abstract]. Am J Respir Crit Care Med 1999 Mar; 159 (3 Pt 2): A640

    Google Scholar 

  123. Dahlén SE, Malmstrom K, Kuna P, et al. Improvement of asthma in aspirin-intolerant patients by montelukast (MK-0476) a potent and specific CYSLT1 receptor antagonist: correlations with patient’s baseline characteristics [abstract]. Eur Respir J 1997 Sep; 10 Suppl. 25: 419S

    Google Scholar 

  124. Reicin AS, Weinstein SF, White R, et al. Montelukast (M) + loratadine(L) compared to M alone provides additional benefit in the treatment of chronic asthma [abstract]. Am J Respir Crit Care Med 1998 Mar; 157 (Pt 2 Suppl.): A416

    Google Scholar 

  125. Edelman JM, Milewski KA, Turpin JA, et al. Effectiveness and safety of montelukast, a leukotriene receptor antagonist, compared to inhaled cromolyn in moderate asthmatic children ages 6 to 11 [abstract no. 510]. J Allergy Clin Immunol 1999 Jan; 103 (1 Pt 2): 134

    Google Scholar 

  126. Volovitz B, Duenas-Meza E, Chmielewska-Szewczyk D, et al. Montelukast versus cromolyn for treatment of 6–11 year old children with asthma [abstract]. Am J Respir Crit Care Med 1999 Mar; 159 (3 Pt 2): A140

    Google Scholar 

  127. Malmstrom K, Meltzer EO, Prenner BP, et al. Concomitant montelukast and loratadine provide rapid significant improvement in seasonal allergic rhinitis compared with loratadine alone [abstract]. Eur Respir J 1998 Sep; 12 Suppl. 28: 274S

    Google Scholar 

  128. Santanello NC, Barber BL, Reiss TF, et al. Measurement characteristics of two asthma symptom diary scales for use in clinical trials. Eur Respir J 1997; 10: 646–51

    PubMed  CAS  Google Scholar 

  129. Santanello NC, Davies G, Galant SP, et al. Validation of an asthma symptom diary for interventional studies. Arch Dis Child 1999 May; 80: 414–20

    Article  PubMed  CAS  Google Scholar 

  130. Sculpher MJ, Buxton MJ. The episode-free day as a composite measure of effectiveness: an illustrative economic evaluation of formoterol versus salbutamol in asthma therapy. Pharmacoeconomics 1993; 4(5): 345–52

    Article  PubMed  CAS  Google Scholar 

  131. Juniper EF, Guyatt GH, Epstein RS, et al. Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials. Thorax 1992; 47: 76–83

    Article  PubMed  CAS  Google Scholar 

  132. Juniper EF, Guyatt GH, Ferrie PJ, et al. Measuring quality of life in asthma. Am Rev Respir Dis 1993; 147: 832–8

    PubMed  CAS  Google Scholar 

  133. Juniper EF, Guyatt GH, Willan A, et al. Determining a minimal important change in a disease-specific quality of life questionnaire. J Clin Epidemiol 1994; 47(1): 81–7

    Article  PubMed  CAS  Google Scholar 

  134. Juniper EF, Guyatt GH, Feeny DH, et al. Measuring quality of life in children with asthma. Qual Life Res 1996; 5: 35–46

    Article  PubMed  CAS  Google Scholar 

  135. Santanello NC, Zhang J, Seidenberg B, et al. What are minimal important changes for asthma measures in a clinical trial? Eur Respir J 1999; 14: 23–7

    Article  PubMed  CAS  Google Scholar 

  136. Reiss TF, Storms W, White R, et al. Montelukast (MK-0476), a CysLT1 receptor antagonist, improves the signs and symptoms of asthma over one year of treatment [abstract]. Allergy Asthma Proc 1998 Jul–Aug; 19: 205–6

    Article  Google Scholar 

  137. Noonan G, Reiss TF, Shingo S, et al. Montelukast (MK-0476) maintains long-term asthma control in adult and pediatric patients (aged ≥6 years) [abstract]. Am J Respir Crit Care Med 1999 Mar; 159 (3 Pt 2): A640

    Google Scholar 

  138. Lu S, Malmstrom K, Wei LX. Effect of montelukast on asthma end points in patients with and without a history of allergic rhinitis [abstract]. J Allergy Clin Immunol 1999 Jan; 103 (Pt 2): 135

    Google Scholar 

  139. Christie PE, Smith CM, Lee TH. The potent and selective sulfidopeptide leukotriene antagonist, SK&F 104353, inhibits aspirin-induced asthma. Am Rev Respir Dis 1991; 144: 957–8

    Article  PubMed  CAS  Google Scholar 

  140. Leukotriene antagonists: a new class of asthma treatment. Curr Probl Pharmacovig 1998 Aug; 24: 14

    Google Scholar 

  141. Reiss TF, Altaian LC, Chervinsky P, et al. Effects of montelukast (MK-0476), a new potent cysteinyl leukotriene (LTD4) receptor antagonist, in patients with chronic asthma. J Allergy Clin Immunol 1996 Sep; 98: 528–34

    Article  PubMed  CAS  Google Scholar 

  142. D’Cruz DP, Barnes NC, Lockwood CM. Difficult asthma or Churg-Strauss syndrome? Steroids may be masking undiagnosed cases of Churg-Strauss syndrome. BMJ 1999 Feb 20; 318: 475–6

    Article  PubMed  Google Scholar 

  143. Haranath SP, Freston C, Fucci M, et al. Montelukast associated Churg-Strauss syndrome [abstract]. Am J Respir Crit Care Med 1999; 159(3): A641

    Google Scholar 

  144. Wechsler ME, Finn D, Jordan M, et al. Montelukast and the Churg-Strauss syndrome [abstract]. Am J Respir Crit Care Med 1999; 159(3): A641

    Google Scholar 

  145. Franco J, Artés MJ. Pulmonary eosinophilia associated with montelukast. Thorax 1999; 54(6): 558–60

    Article  PubMed  CAS  Google Scholar 

  146. Kinoshita M, Shiraishi T, Koga T, et al. Churg-Strauss syndrome after corticosteroid withdrawal in an asthmatic patient treated with pranlukast. J Allergy Clin Immunol 1999 Mar; 103 (3 Pt 1): 534–5

    Article  PubMed  CAS  Google Scholar 

  147. Wechsler ME, Garpestad E, Flier SR, et al. Pulmonary infiltrates, eosinophilia, and cardiomyopathy following corticosteroid withdrawal in patients with asthma receiving zafirlukast. JAMA 1998 Feb 11; 279(6): 455–7

    Article  PubMed  CAS  Google Scholar 

  148. Knoell DL, Lucas J, Allen JN. Churg-Strauss syndrome associated with zafirlukast. Chest 1998 Jul; 114(1): 332–4

    Article  PubMed  CAS  Google Scholar 

  149. Green RL, Vayonis AG. Churg-Strauss syndrome after zafirlukast in two patients not receiving systemic steroid treatment. Lancet 1999 Feb 27; 353(9154): 725–6

    Article  PubMed  CAS  Google Scholar 

  150. Katz RS, Papernik M. Zafirlukast and Churg-Strauss syndrome [letter]. JAMA 1998 Jun 24; 279(24): 1949

    Article  PubMed  CAS  Google Scholar 

  151. Rosenberg JL, Edlow D, Sneider R. Liver disease and vasculitis in a patient taking cromolyn. Arch Intern Med 1978 Jun; 138: 989–91

    Article  PubMed  CAS  Google Scholar 

  152. Löbel H, Machtey I, Eldror MY. Pulmonary infiltrates with eosinophilia in an asthmatic patient treated with disodium cromoglycate [letter]. Lancet 1972 Nov 11; II: 1032

    Article  Google Scholar 

  153. Burgher LW, Kass I, Schenken JR. Pulmonary allergic granulomatosis: a possible drug reaction in a patient receiving cromolyn sodium. Chest 1974 Jul; 66(1): 84–6

    Article  PubMed  CAS  Google Scholar 

  154. Slater EE. Cardiac tamponade and peripheral eosinophilia in a patient receiving cromolyn sodium. Chest 1978 Jun; 73(6): 878

    Article  PubMed  CAS  Google Scholar 

  155. Churg A, Brallas M, Cronin SR, et al. Formes frustes of Churg-Strauss syndrome. Chest 1995; 108: 320–3

    Article  PubMed  CAS  Google Scholar 

  156. Priori R, Tomassini M, Magrini L, et al. Churg-Strauss syndrome during pregnancy after steroid withdrawal. Lancet 1998 Nov 14; 352(9140): 1599–600

    Article  PubMed  CAS  Google Scholar 

  157. Glaxo Wellcome Inc. Flovent (letter to health care professionals)[on line]. [Accessed 29 June, 1999] US Food and Drug Administration. Medwatch. The FDA Medical Products Reporting Program. 21 Jan 1999. Available at http://www.fda.gov/medwatch/safety/1999/floven.htm

  158. Bili A, Condemi JJ, Bottone SM, et al. Seven cases of complete and incomplete forms of Churg-Strauss syndrome not related to leukotriene receptor antagonists. J Allergy Clin Immunol 1999 Nov; 104(5): 1060–5

    Article  PubMed  CAS  Google Scholar 

  159. Martin RM, Wilton LV, Mann RD. Prevalence of Churg-Strauss syndrome, vasculitis, eosinophilia and associated conditions: retrospective analysis of 58 prescription-event monitoring cohort studies. Pharmacoepidemiol Drug Saf 1999; 8: 179–89

    Article  PubMed  CAS  Google Scholar 

  160. Rosenwasser LJ. Leukotriene modifiers: new drugs, old and new reactions [Erratum appears in J Allergy Clin Immunol 1999 Aug; 104 (2 Pt 1)]. J Allergy Clin Immunol 1999; 103 (3 Pt 1): 374–5

    Article  PubMed  CAS  Google Scholar 

  161. Frosi A, Foresi A, Bozzoni M, et al. Churg-Strauss syndrome and antiasthma therapy [letter]. Lancet 1999 Mar 27; 353(9158): 1102

    Article  PubMed  CAS  Google Scholar 

  162. Stirling RG, Chung KF. Leukotriene antagonists and Churg-Strauss syndrome: the smoking gun. Thorax 1999; 54: 865–6

    Article  PubMed  CAS  Google Scholar 

  163. Churg A, Churg J. Steroids and Churg-Strauss syndrome. Lancet 1998 Jul 4; 352(9121): 32–3

    Article  PubMed  CAS  Google Scholar 

  164. Wechsler ME, Pauwels R, Drazen JM. Leukotriene modifiers and Churg-Strauss syndrome: adverse effect or response to corticosteroid withdrawal? Drug Saf 1999 Oct; 21(4): 241–51

    Article  PubMed  CAS  Google Scholar 

  165. Wechsler M, Drazen JM. Churg-Strauss syndrome [letter]. Lancet 1999 Jun 5; 353(9168): 725–6

    Article  Google Scholar 

  166. Merck Pharmaceuticals. Summary of product characteristics. Merck Pharmaceuticals, West Drayton, Middlesex UK, 15 Jan 1998

  167. British Medical Association, Royal Pharmaceutical Society of Great Britain. British National Formulary No. 38. London: The Pharmaceutical Press, 1999 Sep: 125–145

    Google Scholar 

  168. Meijer RJ, Kerstjens HAM, Postma DS. Comparison of guidelines and self-management plans in asthma. Eur Respir J 1997; 10: 1163–72

    Article  PubMed  CAS  Google Scholar 

  169. Bousquet J, Knani J, Henry C, et al. Undertreatment in a non-selected population of adult patients with asthma. J Allergy Clin Immunol 1996 Sep; 98: 514–21

    Article  PubMed  CAS  Google Scholar 

  170. Gaist D, Hallas J, Hansen N-CG, et al. Are young adults with asthma treated sufficiently with inhaled steroids? A population-based study of prescription data from 1991 and 1994. Br J Clin Pharmacol 1996; 41: 285–9

    Article  PubMed  CAS  Google Scholar 

  171. Kauer B, Anderson HR, Austin J, et al. Prevalence of asthma symptoms, diagnosis, and treatment in 12–14 year old children across Great Britain (international study of asthma and allergies in childhood, ISAAC UK). BMJ 1998 Jan 10; 316: 118–24

    Article  Google Scholar 

  172. Ferrante E, Muzzolon R, Fuso L, et al. Bronchial asthma: still an inadequately assessed and improperly treated disease. J Asthma 1994; 31(2): 117–21

    Article  PubMed  CAS  Google Scholar 

  173. Van Ganse E, Hubloue I, Vincken W, et al. Actual use of inhaled corticosteroids and risk of hospitalisation: a case control study. Eur J Clin Pharmacol 1997; 51: 449–54

    Article  PubMed  Google Scholar 

  174. Griffiths C, Naish J, Sturdy P, et al. Prescribing and hospital admissions for asthma in east London. BMJ 1996 Feb 24; 312: 481–2

    Article  PubMed  CAS  Google Scholar 

  175. Doerschug KC, Peterson MW, Dayton CS, et al. Asthma guidelines: an assessment of physician understanding and practice. Am J Respir Crit Care Med 1999; 159: 1735–41

    PubMed  CAS  Google Scholar 

  176. Enright PL, McClelland RL, Newman AB, et al. Underdiagnosis and undertreatment of asthma in the elderly. Chest 1999 Sep; 116(3): 603–13

    Article  PubMed  CAS  Google Scholar 

  177. Lagerløv P, Veninga CCM, Muskova M, et al. Asthma knowledge in five European countries: doctors’ knowledge, attitudes and prescribing behaviour. Eur Respir J 2000; 15: 25–9

    PubMed  Google Scholar 

  178. Jatulis DE, Meng Y-Y, Elashoff RM, et al. Preventive pharmacologic therapy among asthmatics: five years after publication of guidelines. Ann Allergy Asthma Immunol 1998 Jul; 81: 82–8

    Article  PubMed  CAS  Google Scholar 

  179. Legorreta AP, Christian-Herman J, O’Connor RD, et al. Compliance with national asthma management guidelines and specialty care: a health maintenance organization experience. Arch Intern Med 1998 Mar 9; 158: 457–64

    Article  PubMed  CAS  Google Scholar 

  180. Mawhinney H, Spector SL, Kinsman RA, et al. Compliance in clinical trials of two nonbronchodilator, antiasthma medications. Ann Allergy 1991 Apr; 66: 294–9

    PubMed  CAS  Google Scholar 

  181. Kelloway JS, Wyatt RA, Adlis SA. Comparison of patients’ compliance with prescribed oral and inhaled asthma medications. Arch Intern Med 1994 Jun 27; 154: 1349–53

    Article  PubMed  CAS  Google Scholar 

  182. Lipworth BJ. The emerging role of leukotriene antagonists in asthma therapy. Chest 1999 Feb; 115: 313–6

    Article  PubMed  CAS  Google Scholar 

  183. Lipworth BJ. Leukotriene-receptor antagonists. Lancet 1999 Jan 2; 353(9146): 57–62

    Article  PubMed  CAS  Google Scholar 

  184. Lipworth BJ. Modern drug treatment of chronic asthma. BMJ 1999 Feb 6; 318: 380–4

    Article  PubMed  CAS  Google Scholar 

  185. Kercsmar CM. Leukotriene receptor antagonist treatment of asthma: are we there yet? J Pediatr 1999 Mar; 134: 256–9

    Article  PubMed  CAS  Google Scholar 

  186. Scardella AT. Asthma clinical practice guidelines: the evolving role of leukotriene modifiers. Dis Manage Clin Outcomes 1998 Sep–Oct; 1: 161–5

    Article  Google Scholar 

  187. Wenzel SE. Antileukotriene drugs in the management of asthma. JAMA 1998 Dec 23–30; 280: 2068–9

    Article  PubMed  CAS  Google Scholar 

  188. Szefler SJ. Leukotriene modifiers: what is their position in asthma therapy? [editorial]. J Allergy Clin Immunol 1998 Aug; 102: 170–2

    Article  PubMed  CAS  Google Scholar 

  189. Drazen JM, Israel E. Should antileukotriene therapies be used instead of inhaled corticosteroids in asthma? Yes [editorial]. Am J Respir Crit Care Med 1998 Dec; 158: 1697–8

    PubMed  CAS  Google Scholar 

  190. Wenzel SE. Should antileukotriene therapies be used instead of inhaled corticosteroids in asthma? No [editorial]. Am J Respir Crit Care Med 1998 Dec; 158: 1699–701

    PubMed  CAS  Google Scholar 

  191. Smith LJ. Newer asthma therapies [editorial]. Ann Intern Med 1999 Mar 16; 130(6): 531–2

    PubMed  CAS  Google Scholar 

  192. Nathan RA, Minkwitz MC, Bonuccelli CM. Two first-line therapies in the treatment of mild asthma: use of peak flow variability as a predictor of effectiveness. Ann Allergy Asthma Immunol 1999 May; 82: 497–503

    Article  PubMed  CAS  Google Scholar 

  193. Dworski R, Fitzgerald GA, Oates JA, et al. Effect of oral prednisone on airway inflammatory mediators in atopic asthma. Am J Respir Crit Care Med 1994; 149: 953–9

    PubMed  CAS  Google Scholar 

  194. Manso G, Baker AJ, Taylor IK, et al. In vivo and in vitro effects of glucocorticoids on arachidonic acid metabolism and monocyte function in nonasthmatic humans. Eur Respir J 1992; 5: 712–6

    PubMed  CAS  Google Scholar 

  195. O’Shaughnessy KM, Wellings R, Gillies B, et al. Differential effects of fluticasone propionate on allergen-evoked bronchoconstriction and increased urinary leukotriene E4 excretion. Am Rev Respir Dis 1993; 147: 1472–6

    PubMed  Google Scholar 

  196. Riddick CA, Ring WL, Baker JR, et al. Dexamethasone increases expression of 5-lipoxygenase and its activating protein in human monocytes and THP-1 cells. Eur J Biochem 1997 May 15; 246(1): 112–8

    Article  PubMed  CAS  Google Scholar 

  197. Tamaoki J, Kondo M, Sakai N, et al. Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. Am J Respir Crit Care Med 1997; 155: 1235–40

    PubMed  CAS  Google Scholar 

  198. Nayak AS, Anderson P, Charous BL, et al. Equivalence of adding zafirlukast versus double-dose inhaled corticosteroids in asthmatic patients symptomatic on low-dose inhaled corticosteroids [abstract no. 965]. J Allergy Clin Immunol 1998 Jan; 101 (1 Pt 2): S223

    Article  Google Scholar 

  199. Bateman ED, Holgate ST, Binks SM, et al. A multicentre study to assess the steroid-sparing potential of accolate (zafirlukast; 20 mg bd) [abstract no. P-0709]. Allergy 1995; 50 Suppl. 26: 320

    Google Scholar 

  200. Laitinen LA, Zetterström O, Holgate ST, et al. Effects of ACCOLATE (zafirlukast; 20 mg bd) in permitting reduced therapy with inhaled steroids: a multicenter trial in patients with doses of inhaled steroid optimised between 800 and 2000 mcg per day [abstract no. p-0710]. Allergy 1995; 50 Suppl. 26: 320

    Google Scholar 

  201. Tattersfield AE, Harrison TW. Step 3 of the asthma guidelines [editorial]. Thorax 1999; 54: 753–4

    Article  PubMed  CAS  Google Scholar 

  202. Cumming RG, Mitchell P, Leeder SR. Use of inhaled corticosteroids and the risk of cataracts. N Engl J Med 1997 Jul 3; 337(1): 8–14

    Article  PubMed  CAS  Google Scholar 

  203. Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy: a systematic review and meta-analysis. Arch Intern Med 1999 May 10; 159: 941–55

    Article  PubMed  CAS  Google Scholar 

  204. Ledford D, Apter A, Brenner AM, et al. Osteoporosis in the corticosteroid-treated patient with asthma. J Allergy Clin Immunol 1998; 102: 353–62

    Article  PubMed  CAS  Google Scholar 

  205. Garbe E, Suissa S, LeLorier J. Association of inhaled corticosteroid use with cataract extraction in elderly patients. JAMA 1998 Aug 12; 280(6): 539–43

    Article  PubMed  CAS  Google Scholar 

  206. Garbe E, LeLorier J, Boivin J-F, et al. Inhaled and nasal glucocorticoids and the risks of ocular hypertension or open-angle glaucoma. JAMA 1997 Mar 5; 9: 722–7

    Article  Google Scholar 

  207. Russell G. Inhaled corticosteroid therapy in children: an assessment of the potential for side effects. Thorax 1994; 49: 1185–8

    Article  PubMed  CAS  Google Scholar 

  208. O’Byrne P. Are new asthma therapies needed? J Clin Pharmacol 1999; 39: 230–6

    PubMed  Google Scholar 

  209. McCowan C, Neville RG, Thomas GE, et al. Effect of asthma and its treatment on growth: four year follow up of cohort of children from general practices in Tayside, Scotland. BMJ 1998 Feb 28; 316: 668–72

    Article  PubMed  CAS  Google Scholar 

  210. Russell G. Childhood asthma and growth — a review of the literature. Respir Med 1994; 88 Suppl. A: 31–7

    Article  PubMed  Google Scholar 

  211. Agertoft L, Pedersen S. Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Respir Med 1994; 88: 373–81

    Article  PubMed  CAS  Google Scholar 

  212. Brook CGD. Short stature never killed anybody [editorial]. J Pediatr 1998 Nov; 133: 591–2

    Article  PubMed  CAS  Google Scholar 

  213. Heuck C, Wolthers OD, Kollerup G, et al. Adverse effects of inhaled budesonide (800 mcg) on growth and collagen turnover in children with asthma: a double-blind comparison of once-daily versus twice-daily administration. J Pediatr 1998 Nov; 133(5): 608–12

    Article  PubMed  CAS  Google Scholar 

  214. Wagener JS, Wojtczak HA. Inhaled steroids in children: risks versus rewards [editorial]. J Pediatr 1998 Mar; 132 (3 Pt 1): 381–3

    Article  PubMed  CAS  Google Scholar 

  215. Crowley S, Trivedi P, Risteli L, et al. Collagen metabolism and growth in prepubertal children with asthma treated with inhaled steroids. J Pediatr 1998 Mar; 132 (3 Pt 1): 409–15

    Article  PubMed  CAS  Google Scholar 

  216. Doull IJM, Campbell MJ, Holgate ST. Duration of growth suppressive effects of regular inhaled corticosteroids. Arch Dis Child 1998 Feb; 78: 172–3

    Article  PubMed  CAS  Google Scholar 

  217. Harding SM. The dull-edged sword of inhaled corticosteroids. Chest 1999 Oct; 116: 854–6

    Article  PubMed  CAS  Google Scholar 

  218. Evans DJ, Taylor DA, Zetterstrom O, et al. A comparison of low-dose inhaled budesonide plus theophylline and high dose inhaled budesonide for moderate asthma. N Engl J Med 1997 Nov 13; 337(20): 1412–8

    Article  PubMed  CAS  Google Scholar 

  219. Weinberger M, Hendeles L. Theophylline in asthma. N Engl J Med 1996 May 23; 334(21): 1380–8

    Article  PubMed  CAS  Google Scholar 

  220. Markham A, Faulds D. Theophylline: a review of its potential steroid sparing effects in asthma. Drugs 1998 Dec; 56: 1081–91

    Article  PubMed  CAS  Google Scholar 

  221. Shannon M. Life-threatening events after theophylline overdose: a 10-year prospective analysis. Arch Intern Med 1999 May 10; 159: 989–94

    Article  PubMed  CAS  Google Scholar 

  222. McFadden Jr ER, Gilbert IA. Exercise-induced asthma. N Engl J Med 1994 May 12; 330(19): 1362–7

    Article  PubMed  Google Scholar 

  223. Cabral ALB, Conceição GM, Fonseca-Guedes CHF, et al. Exercise-induced bronchospasm in children: effects of asthma severity. Am J Respir Crit Care Med 1999; 159: 1819–23

    PubMed  CAS  Google Scholar 

  224. Menendez R, Venzor J, Ortiz G. Failure of zafirlukast to prevent ibuprofen-induced anaphylaxis. Ann Allergy Asthma Immunol 1998 Mar; 80: 225–2226

    Article  PubMed  CAS  Google Scholar 

  225. Nathan RA, Bernstein JA, Bielory L, et al. Zafirlukast improves asthma symptoms and quality of life in patients with moderate reversisble airflow obstruction. J Allergy Clin Immunol 1998 Dec; 102 (6 Pt 1): 935–42

    Article  PubMed  CAS  Google Scholar 

  226. Tashkin DP, Nathan RA, Howland WC, et al. An evaluation of zafirlukast in the treatment of asthma with exploratory subset analyses. J Allergy Clin Immunol 1999 Feb; 103 (2 Pt 1): 246–54

    Article  PubMed  CAS  Google Scholar 

  227. Kemp JP, Minkwitz MC, Bonuccelli CM, et al. Therapeutic effect of zafirlukast as monotherapy in steroid-naive patients with severe persistent asthma. Chest 1999 Feb; 115: 336–42

    Article  PubMed  CAS  Google Scholar 

  228. Fish JE, Kemp JP, Lockey RF, et al. Zafirlukast for symptomatic mild-to-moderate asthma: a 13-week multicenter study. Clin Ther 1997 Jul–Aug; 19(4): 675–90

    Article  PubMed  CAS  Google Scholar 

  229. Liu MC, Dube LM, Lancaster J. Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: a 6-month randomized multicenter trial. Zileuton Study Group. J Allergy Clin Immunol 1996 Nov; 98 (5 Pt 1): 859–71

    Article  PubMed  CAS  Google Scholar 

  230. Israel E, Cohn J, Dube L, et al. Effect of treatment with zileuton, a 5-lipoxygenase inhibitor, in patients with asthma. A randomized controlled trial Zileuton Clinical Trial Group. JAMA 1996 Mar 27; 275(12): 931–6

    CAS  Google Scholar 

  231. Barnes NC, Pujet J-C. Pranlukast, a novel leukotriene receptor antagonist: results of the first European, placebo controlled, multicentre clinical study in asthma. Thorax 1997; 52: 523–7

    Article  PubMed  CAS  Google Scholar 

  232. Grossman J, Faiferman I, Dubb JW, et al. Results of the first U.S. double-blind, placebo-controlled, multicenter clinical study in asthma with pranlukast, a novel leukotriene receptor antagonist. J Asthma 1997; 34(4): 321–8

    CAS  Google Scholar 

  233. Barnes NC. Effects of antileukotrienes in the treatment of asthma. Am J Respir Crit Care Med 2000; 161 Suppl.: S73–6

    PubMed  CAS  Google Scholar 

  234. Schwartz HJ, Petty T, Dube LM, et al. A randomized controlled trial comparing zileuton with theophyllin in moderate asthma. The Zileuton Study Group. Arch Intern Med 1998 Jan 26; 1998 (2): 141–8

  235. Busse W, Nelson H, Wolfe J, et al. Comparison of inhaled salmeterol and oral zafirlukast in patients with asthma. J Allergy Clin Immunol 1999 Jun; 103(6): 1075–80

    Article  PubMed  CAS  Google Scholar 

  236. AstraZeneca. Accolate (zafirlukast) prescribing information. AstraZeneca, Wilmington, Delaware, USA, Mar, 1999

  237. Abbott Laboratories. Zyflo (zileuton) prescribing information. Abbott Laboratories, North Chicago, Illinois, 60064 USA, Mar, 1998

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  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 10, New Zealand

    Blair Jarvis

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  1. Blair Jarvis
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Correspondence to Blair Jarvis.

Additional information

Various sections of the manuscript reviewed by: N.C. Barnes, The Royal Hospitals NHS Trust, Department of Respiratory Medicine, The London Chest Hospital, London, England; P.J. Barnes, Department of Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, England; E. Bateman, University of Cape Town and Respiratory Clinic Groote Schuur Hospital, Cape Town, South Africa; A. Becker, Section of Allergy and Clinical Immunology, Children’s Hospital of Winnipeg, Winnipeg, Manitoba, Canada; Z. Diamant, Department of Pulmonology, Erasmus University Medical Center, Rotterdam, The Netherlands; P.H. Godard, Hopital Universitaire Aiguelongue, Montpellier, France; J.P. Kemp, Allergy and Asthma Medical Group and Research Center, San Diego, California, USA; G.G. Shapiro, A.S.T.H.M.A., Inc., Northwest Asthma and Allergy Center, Seattle, Washington, USA; R.G. Stirling, Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, England.

Data Selection

Sources: Medical literature published in any language since 1966 on montelukast, identified using AdisBase (a proprietary database of Adis International, Auckland, New Zealand), Medline and EMBASE. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: AdisBase, Medline and EMBASE search terms were ‘montelukast’, ‘MK-476’, ‘MK-0476’, ‘L-706631’, ‘Singulair’ and ‘asthma’. Searches were last updated 20 Mar 2000.

Selection: Studies in patients with asthma who received montelukast. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Asthma, montelukast, pharmacodynamics, pharmacokinetics, therapeutic use.

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Jarvis, B., Markham, A. Montelukast. Drugs 59, 891–928 (2000). https://doi.org/10.2165/00003495-200059040-00015

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