- 110 Downloads
Pranlukast (Onon®, Azlaire®), is an orally administered, selective, competitive antagonist of the cysteinyl leukotrienes (LT) C4, LTD4 and LTE4. It is indicated for the prophylactic treatment of chronic bronchial asthma in paediatric and adult patients.
The efficacy of pranlukast 225mg twice daily in adults with mild to moderate asthma was demonstrated in double-blind, placebo- or azelastine-controlled studies of 4 or 8 weeks' duration. The drug at this dosage was superior to both comparators in improving mean attack scores and morning and/or evening peak expiratory flow rates, and decreasing the use of rescue bronchodilators (p < 0.05). In limited clinical studies, pranlukast 225mg twice daily appeared to be as effective as montelukast 10mg once daily and zafirlukast 40mg twice daily in adults with mild to moderate asthma. Tachyphylaxis was absent when the drug was administered for up to 4 years. In patients requiring high-dose inhaled corticosteroid therapy, pranlukast 225mg twice daily plus a halved dosage of inhaled corticosteroid was as effective as the original dosage of inhaled corticosteroid. Pranlukast was also effective in patients with mild to severe asthma in a clinical practice setting. In a double-blind trial, greater improvements in most outcome measures were observed with pranlukast than with oxatomide in children and adolescents with asthma.
In clinical trials, pranlukast was well tolerated in adult and paediatric patients with asthma, with an adverse event profile similar to that of placebo. Gastrointestinal events and hepatic function abnormalities were the most commonly reported adverse events. No clinically significant differences in adverse event profiles between pranlukast, zafirlukast or montelukast were shown in limited comparisons. Although Churg-Strauss syndrome has been noted in pranlukast recipients, a direct causal relationship is unlikely.
Conclusions: Pranlukast is a well tolerated and effective preventative treatment in adult and paediatric patients with persistent asthma of all severities. In some patients, pranlukast may be beneficial when added to low-dose inhaled corticosteroids; it may also be a viable alternative to increasing inhaled corticosteroid dosages. The efficacy of pranlukast relative to placebo has been confirmed; its efficacy relative to other therapy awaits further investigation. Nonetheless, pranlukast is a useful therapeutic option (with as-required short-acting β2-agonists), either as preventative monotherapy for the treatment of mild persistent asthma or in conjunction with inhaled corticosteroids in the management of moderate or severe persistent asthma.
Pranlukast is a selective, competitive antagonist of the cysteinyl leukotrienes, leukotriene (LT) C4, LTD4 and LTE4, antagonising binding at the cysteinyl leukotriene type 1 (CysLTi) receptor. Like the other commercially-available CysLTi receptor antagonists montelukast and zafirlukast, pranlukast inhibits antigen-induced contraction of human bronchial smooth muscle in vitro.
In patients with asthma, oral pranlukast at clinically relevant dosages generally inhibited eosinophil activity and the presence of eosinophils in sputum (in the late asthma response), reduced exhaled nitric oxide levels, improved allergen-induced decreases in forced expiratory volume in 1 second and reduced the magnitude of airway hyperresponsiveness.
Pranlukast attenuated bronchoconstriction induced by exercise (dosage of 450 mg/day for 14 days), LTD4 (pranlukast 10-60mg as a single intravenous dose), aspirin (pranlukast 450 mg/day for 7 days), and bronchial hyperresponsiveness induced by methacholine and cold air (clinically relevant dosages), but did not ameliorate the effects of histamine, alcohol or propranolol.
At least 12.5% of a dose of pranlukast is absorbed after oral administration, and maximum plasma concentrations are achieved within 2-6 hours when the drug is administered after food. Steady-state plasma concentrations of pranlukast are achieved within 7 days of twice-daily oral administration. Bioavailability is increased when the drug is administered before or after a meal; in addition, the bioavailability of pranlukast is greater after evening than after morning administration. Pranlukast is approximately 99% bound to plasma protein.
The mean plasma elimination half-life of oral pranlukast ranged from 3-9 hours after repeated doses in pharmacokinetic studies. The drug is cleared through metabolic transformation (primarily glucuronic acid conjugation). The majority of an oral dose is excreted via the faecal route, chiefly as the unchanged drug, within 72 hours of administration.
The pharmacokinetics of a single dose of oral pranlukast were generally similar in adults with asthma, elderly (aged >65 years) or young (aged 18-35 years) volunteers and, on a mg/kg basis, in children aged 8-11 years with moderate asthma.
Although the drug is metabolised by cytochrome P450 (CYP) enzymes in vitro, in a clinical setting pranlukast appears to have low potential for drug-drug interactions via this system. Urinary 6β-hydroxycortisol excretion (a surrogate marker of CYP3A4 activity) was unchanged with oral pranlukast 112.5-675mg twice daily in healthy volunteers. Prior treatment with clinically relevant doses of oral pranlukast (225mg twice daily) had no effect on the pharmacokinetics of intravenous aminophylline administered 4 hours after the final dose of pranlukast in healthy young adults.
In Adults: In patients with mild to moderate asthma receiving bronchodilators and/or inhaled corticosteroids, pranlukast 225mg twice daily for 4 or 8 weeks was more effective in improving asthma symptoms than twice-daily administration of placebo or azelastine 2mg. Mean attack scores, morning or evening peak expiratory flow rate (PEFR) and frequency of bronchodilator use improved to a significantly greater extent (p <0.05) with pranlukast than with placebo or azelastine at each 2-week timepoint in two randomised, double-blind, multicentre 4- or 8-week trials (n = 197 and 177).
In randomised, double-blind trials in patients with mild to moderate asthma, pranlukast 225mg twice daily showed similar efficacy to zafirlukast 40mg twice daily for 6 weeks in 298 patients and montelukast 10mg once daily for 4 weeks in 368 patients.
A subgroup analysis of preliminary data from European and US efficacy trials demonstrated that pranlukast 75–450mg twice daily for 12 weeks was effective in patients (n = 941–949) with mild to moderate asthma complicated by rhinitis.
In small (n = 10–70), nonblind 4- to 16-week studies, pranlukast 225mg twice daily was generally effective in patients with moderate or severe asthma receiving a concomitant inhaled corticosteroid (but not in those also receiving oral prednisolone) and in patients with severe asthma refractory to corticosteroids.
Patients with mild to severe asthma who were responders to pranlukast (>15% increase in baseline PEFR after 16 weeks' treatment) have been effectively treated with pranlukast for up to 4 years. Patients receiving pranlukast had a significantly greater increase in percentage of predicted PEFR than patients receiving conventional therapy over the 4-year period.
Pranlukast allows for reduced inhaled corticosteroid dosages without deterioration in lung function in patients requiring high-dose inhaled corticosteroids. In a randomised, double-blind, placebo-controlled, 6-week trial in 79 patients with stable asthma who had been receiving inhaled beclomethasone ≥1500 µg/day, outcome measures did not change significantly from baseline values when inhaled corticosteroid doses were halved in patients receiving pranlukast 225mg twice daily. In contrast, a significant deterioration in outcome measures was demonstrated by patients receiving placebo. Similar results were observed in 8- and 16-week randomised trials.
Health-related quality of life (HRQOL) improved in adult patients with asthma receiving pranlukast 225–450mg twice daily in a placebo-controlled 12-week trial or nonblind 4- to 12-week trials.
In Children: Pranlukast was at least as effective as the H1 antihistamine oxatomide in a randomised, double-blind 4-week trial in 214 patients aged >1 year with mild to severe paediatric asthma. Pranlukast ≈7 mg/kg/day had a significantly better final global improvement rating than oxatomide ≈1 mg/kg/day (71.4% vs 37.2%) in both per-protocol and intention-to-treat analyses and was superior for several, but not all, other parameters.
In longer nonblind studies, treatment with pranlukast dry syrup for up to 24 months improved asthma control compared with baseline values.
Pranlukast dry syrup improved overall HRQOL, physical domain and emotional domain scores from baseline in children with mild to moderate asthma aged <4 years (n = 20; mean age 2.0 years) and ≥4 years (n = 36; mean age 6.6 years) in a nonblind, 4-week trial.
In Clinical Practice: Pranlukast was effective in the treatment of mild to severe asthma symptoms in the clinical practice setting, as shown by a large (completed by >2500 patients), nonblind, population-based study without specific inclusion and exclusion criteria. The efficacy of pranlukast was unaffected by concomitant use of inhaled corticosteroids, β2-agonists and/or theophylline.
Preliminary data from retrospective Japanese pharmacoeconomic studies suggest that pranlukast may be a cost-effective addition to asthma treatment. Relative to placebo, pranlukast reduced the cost required to obtain an effectiveness increase of one point regardless of whether direct or overall costs were considered in a 4-week study in 166 patients with mild to moderate asthma (currency year 1995).
The initiation of pranlukast 225mg twice daily increased annual medication costs compared with the year before in 30 patients with moderate or severe asthma who responded to pranlukast, despite decreased asthma symptoms and signs.
Pranlukast was well tolerated in clinical trials in adults or children with asthma; most adverse events were experienced by <1 % of patients. In pre-approval clinical trials of pranlukast conducted in Japan, 7.4% of 472 evaluated adult patients and 5.6% of 320 evaluated paediatric patients with asthma reported an adverse event with pranlukast treatment. Gastrointestinal adverse events (e.g. nausea, diarrhoea, abdominal pain/stomach discomfort) and hepatic function abnormalities were the most commonly reported adverse events. In comparative trials, the frequency of adverse events with pranlukast was significantly less than with azelastine in adult patients (12.2% vs 26.4%), and similar to that with oxatomide dry syrup in paediatric patients (9.4% vs 11.1 %). Moreover, the frequency, severity and nature of adverse events with pranlukast 225–450mg twice daily were similar to those with placebo in clinical trials in Europe and the US.
In long-term treatment (for up to 4 years) in adult patients, pranlukast was well tolerated and laboratory data did not change significantly.
Comparative clinical studies have shown no clinically significant differences in adverse event profiles between pranlukast and zafirlukast or montelukast.
Churg-Strauss syndrome, a form of vasculitis, has been noted in patients receiving pranlukast; however, it is unlikely that there is a direct causal relationship between the drug and the emergence of this condition.
Dosage and Administration
Oral pranlukast is indicated for the prophylactic treatment of chronic bronchial asthma in Japan and for the prophylaxis and treatment of chronic bronchial asthma, including the prevention of exercise-induced asthma, in Latin America. It is approved for use in a capsule formulation in adult patients in Japan and in those aged ≥12 years in Latin America, and as a dry syrup formulation in paediatric patients aged ≥1 year (in Japan) or ≥2 years (Latin America). The recommended dosage of pranlukast is 450 mg/day in adult patients and 7 mg/kg/day (increasing to a maximum of 10 mg/kg/day according to age and symptoms, but not exceeding 450 mg/day) in paediatric patients, divided into two doses. As food affects the bioavailability of pranlukast, the drug is administered after breakfast and dinner. The manufacturer's prescribing information states that pranlukast should be withdrawn in patients with suspected liver dysfunction, interstitial or eosinophilic pneumonia, leukopenia, thrombocytopenia or risk of anaphylaxis. Close monitoring is required when the drug is administered in patients undergoing dosage reduction or withdrawal of oral corticosteroids. Dosage adjustments are recommended in elderly patients, and caution is required when prescribing pranlukast during pregnancy or when it is coadministered with drugs that are predominantly metabolised by or inhibit the activity of CYP3A4 enzymes.
KeywordsAsthma Montelukast Beclomethasone Peak Expiratory Flow Rate Zafirlukast
- 1.National Institutes of Health. Global initiative for asthma: global strategy for asthma management and prevention [online]. Available from URL: http://www.ginasthma.com [Accessed 2002 Oct 10]
- 3.O'Byrne PM. Leukotriene bronchoconstriction induced by allergen and exercise. Am J Respir Crit Care Med 2000; 161 (2): S68–72Google Scholar
- 4.Kumlin M. Measurement of leukotrienes in humans. Am J Respir Crit Care Med 2000; 161 (2): S102–6Google Scholar
- 6.Kellaway CH, Trethewie ER. The liberation of a slow reacting smooth-muscle-stimulating substance in anaphylaxis. Q J Exp Physiol 1940; 30: 121–45Google Scholar
- 8.Samuelsson B. The discovery of the leukotrienes. Am J Respir Crit Care Med 2000; 161 (2): S2–6Google Scholar
- 15.Nothacker H-P, Wang Z, Zhu Y, et al. Molecular cloning and chararacterization of a second human cysteinyl leukotriene receptor: discovery of a subtype selective agonist. Mol Pharmacol 2000; 58(6): 1601–8Google Scholar
- 21.Dahlén S-E. Pharmacological characterization of leukotriene receptors. Am J Respir Crit Care Med 2000; 161 (2): S41–5Google Scholar
- 24.Zhang M-Q, Zwaagstra ME. Structural requirements for leukotriene CysLT1 receptor ligands. Curr Med Chem 1997; 4(4): 229–46Google Scholar
- 46.Panettieri RA, Leonard T, Luttmann MA, et al. Pranlukast, but not montelukast, inhibits LTD4-induced potentiation of human airway smooth muscle proliferation [abstract]. Eur Respir J 1997 Sep; 10 Suppl. 25: 438SGoogle Scholar
- 47.Nakagawa N, Fujita M, Yonetomi Y, et al. CysLT1 antagonism of pranlukast, montelukast and zafirlukast in the presence of serum albumin [in Japanese]. Jpn Pharmacol Ther 2002; 30(3): 191–5Google Scholar
- 50.ObataT, Nambu F, Kitagawa T, et al. ONO-1078: an antagonist of leukotrienes. Adv Prostaglandin Thromboxane Leukot Res 1987; 17A: 540–3Google Scholar
- 53.Kurosawa M, Yodonawa S, Tsukagoshi H, et al. Inhibition by a novel peptide leukotriene receptor antagonist ONO-1078 of airway wall thickening and airway hyperresponsiveness to histamine induced by leukotriene C4 or leukotriene D4 in guinea-pigs. Clin Exp Allergy 1994 Oct; 24(10): 960–8PubMedCrossRefGoogle Scholar
- 62.Underwood DC, Osborn RR, Newsholme SJ, et al. Persistent airway eosinophilia after leukotriene (LT) D4 administration in the guinea pig: modulation by the LTD4 receptor antagonist, pranlukast, or an interleukin-5 monoclonal antibody. Am J Respir Crit Care Med 1996 Oct; 154 (4 Pt 1): 850–7PubMedGoogle Scholar
- 66.Hozawa S, Haruta Y, Tamagawa K, et al. Effect of a LT receptor antagonist, ONO-1078, on bronchial hyperrespon-siveness and serum ECP in patients with asthma. Am J Respir Crit Care Med 1998 Mar; 157 Suppl. Pt 2: 413Google Scholar
- 67.Yoshikawa T, Hirata K, Shiraishi S, et al. Effect of pranlukast on airway eosinophilic inflammation in patients with asthma: a randomized double-blind, placebo-controlled trial [abstract]. Am J Respir Crit Care Med 1999 Mar; 159 Suppl. Pt 2: 641Google Scholar
- 68.Isogai S, Taniguchi M, Anzai K, et al. Effects of peptido-leukotriene receptor antagonist, pranlukast on eosinophil counts in peripheral blood and sputum in patients with chronic asthma [abstract]. Am J Respir Crit Care Med 1998 Mar; 157 Suppl. Pt 2: 412Google Scholar
- 78.Smith LJ, Jorkasky DK, Carr A, et al. Intravenous pranlukast (Ultair) inhibits LTD4-induced bronchoconstriction in patients with asthma [abstract]. J Allergy Clin Immunol 1997 Jan; 99 (Pt 2): 328Google Scholar
- 82.Strek ME, Sedy J, Solway J, et al. Pranlukast (Ultair) inhibits cold air-induced bronchoconstriction in patients with asthma [abstract]. J Allergy Clin Immunol 1997 Jan; 99 (Pt 2): 329Google Scholar
- 83.Shimoda TS, Asai SA, Kohno SK. Inhibitory effects of antiallergic drugs in alcohol-induced asthma [abstract]. Allergy Clin Immunol Int 2000; Suppl. 2: 126–7Google Scholar
- 86.Ohmichi M, Tanaka H, Tanaka S, et al. Sputum eosinophil cationic protein, interleukin-8 and urinary eicosanoids in asthmatic patients with a long term treatment of pranlukast [abstract]. Eur Respir J 1998 Sep; 12 Suppl. 28: 361Google Scholar
- 87.Ramsay CF, van Kan CI, Sterk PJ, et al. Pranlukast improves spirometry and bronchial hyperresponsiveness in patients with mild asthma [abstract]. Am J Respir Crit Care Med 1998 Mar; 157 Suppl. Pt 2: 411Google Scholar
- 89.Hirata K, Kurihara N, Kamimori T, et al. Exercise-induced asthma and leukotriene receptor antagonist [in Japanese]. Rinsho Iyaku 1993; 9 Suppl. 1: 225–8Google Scholar
- 90.Christie PE, Tagari P, Ford-Hutchison AW, et al. Urinary leukotriene E4 concentrations increase after aspirin challenge in aspirin-sensitive asthmatic subjects. Am Rev Respir Dis 1994; 143: 1025–9Google Scholar
- 92.Sano Y, Suzuki N, To M, et al. Effects of pranlukast hydrate on allergic airway inflammation in patients with mild to moderate asthma [abstract]. Allergy Clin Immunol Int 2000; Suppl. 2: 48Google Scholar
- 96.Nakashima M, Uematsu T, Kanamaru M, et al. A phase I clinical study of a leukotriene C4, D4 and E4 receptor antagonist; ONO-1078 in healthy volunteers [in Japanese]. Rinsho Iyaku 1993; 9 Suppl. 1: 3–29Google Scholar
- 97.Kemp JP, Tinkelman D, Sublett J, et al. Pranlukast (Ultair) pharmacokinetics in children consistent with that of adults. Am J Respir Crit Care Med 1998 Mar; 157 Suppl. Pt 2: 411Google Scholar
- 98.Dennis M, Minthorn E, Stelman G, et al. Effect of food on the absorption of pranlukast in healthy subjects. Pharm Res 1994 Oct; 11 Suppl.: 430Google Scholar
- 99.Murdoch RD, Upward JW, Dennis M, et al. The safety and pharmacokinetics of IV aminophylline during co-administration with an oral LTD4 receptor antagonist pranlukast [abstract]. Eur Respir J 1995 Sep; 8 Suppl. 19: 48SGoogle Scholar
- 100.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): 321–8Google Scholar
- 101.PLM Latina. Azlaire capsulas [online]. Available from URL: http://www.plmlatina.com/sp/sp_alz.htm [Accessed 2002 Dec 19]
- 104.The Japan Pharmaceutical Manufacturers Association. Japan Pharmaceutical Reference: Onon capsules [online]. Available from URL: http://www.jpma.or.jp/jpr/ [Accessed 2002 Oct 29]
- 106.Chervinsky P, Wenzel S, Kerwin E, et al. Pranlukast, a leukotriene receptor antagonist, improves quality of life in adult asthma patients [abstract]. Eur Respir J 1997 Sep; 10 Suppl. 25: 439SGoogle Scholar
- 107.Korenblat P, Wenzel S, Chervinsky P, et al. Reduction in health care utilization associated with pranlukast in adult patients with asthma [abstract]. Eur Respir J 1997 Sep; 10 Suppl. 25: 439Google Scholar
- 108.Spector SL, Bronsky E, Faiferman I, et al. Pranlukast (Ultair) decreases symptoms in patients with asthma complicated by rhinitis [abstract]. Am J Respir Crit Care Med 1998 Mar; 157 Suppl. Pt 2: A617Google Scholar
- 109.Silvers WS, Strek ME, Faiferman I, et al. Pranlukast (Ultair) decreases beta-2-agonist use in patients with asthma complicated by rhinitis [abstract]. Am J Respir Crit Care Med 1998 Mar; 157 Suppl. Pt 2: A617Google Scholar
- 110.Rosenthal R, Lang DM, Faiferman I, et al. Pranlukast (Ultair) improves lung function in patients with asthma complicated by rhinitis [abstract]. Am J Respir Crit Care Med 1998 Mar; 157 Suppl. Pt 2: A617Google Scholar
- 114.Miyamoto T, Nakajima S, Mano K, et al. Phase III comparative study of ICI 204,219 (zafirlukast, Accolate), a cysteinyl-leukotriene (LT) receptor antagonist, in adult patients with bronchial asthma: a double-blind comparative study with pranlukast hydrate. Rinsho Iyaku 2001; 17(12): 1683–723Google Scholar
- 118.Tamaoki J, Kondo M, Sakai N, et al. Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. The Tokyo Joshi-Idai Asthma Research Group. Am J Respir Crit Care Med 1997 Apr; 155(4): 1235–40Google Scholar
- 119.Mikawa H, Baba M, Nakashima M. Clinical usefulness of a leukotriene antagonist; pranlukast dry syrup on pediatric bronchial asthma in multi-center comparative double-blind clinical study with oxatomide dry syrup [in Japanese]. Rinsho Iyaku 1997; 13(2): 423–56Google Scholar
- 120.Miyamoto T, Takishima T, Makino S, et al. Utility of a leukotrienes C4, D4 and E4 antagonist; ONO-1078, on adult bronchial asthma in multi-center comparative double-blind study with azelastine hydrochloride [in Japanese]. Rinsho Iyaku 1993; 9 Suppl. 1: 71–107Google Scholar
- 121.Toyoshima K, Kameda M, Mikawa H, et al. Efficacy and safety of a long-term (12 weeks) use of a leukotriene C4, D4 and E4 antagonist, ONO-1078 dry syrup, in asthmatic children [in Japanese]. Rinsho Iyaku 1997; 13(4): 1041–71Google Scholar
- 122.Iikura Y, Saito H, Sakaguchi N, et al. Efficacy and safety of a long-term use of a leukotriene C4, D4 and E4 antagonist, ONO-1078 dry syrup, in pediatric bronchial asthma [in Japanese]. Rinsho Iyaku 1997; 13(4): 1015–39Google Scholar
- 123.Tomita K, Hashimoto K, Matsumoto S, et al. Pranlukast allows reduction of inhaled steroid dose without deterioration in lung function in adult asthmatics [in Japanese]. Jpn J Allergol 1999 Apr; 48(4): 459–65Google Scholar
- 124.Tamura G, Iwasaki T, Shirato K, et al. Effect of pranlukast, a CysLTl receptor antagonist, on asthmatics treated with high doses of inhaled beclomethasone [abstract]. Allergy Clin Immunol Int 2000; Suppl. 2: 136Google Scholar
- 125.Takahashi H, Odagiri S, Yoshiike Y, et al. Pranlukast improves quality of life in patients treated with fluticasone propionate [abstract]. Allergy Clin Immunol Int 2000; Suppl. 2: 125Google Scholar
- 126.Terashima T, Yamaguchi K. Effect of pranlukast on health-related quality of life in patients with moderate persistent asthma [poster]. Am J Respir Crit Care Med 2002 Apr; 165 (Pt 2): 186Google Scholar
- 127.Yano T, Arikawa K, Saito S, et al. Clinical evaluation of the leukotriene receptor antagonist (Pranlukast) on health-related quality of life in patients with asthma [abstract]. Am J Respir Crit Care Med 1999 Mar; 159 Suppl. Pt 2: 641Google Scholar
- 129.Calhoun WJ, Weisberg SC, Faiferman I, et al. Pranlukast (Ultair) is effective in improving asthma: results of a 12-week, multicenter, dose-range study [abstract]. J Allergy Clin Immunol 1997 Jan; 99 (Pt 2): 318Google Scholar
- 130.Miyamoto T, Takishima T, Tamura G, et al. Dose finding study of leukotriene antagonist; ONO-1078, on adult bronchial asthma [in Japanese]. Rinsho Iyaku 1993; 9 Suppl. 1: 53–70Google Scholar
- 131.Miyamoto T, Takishima T, Tamura G, et al. Efficacy and safety of leukotriene antagonist; ONO-1078, on adult bronchial asthma [in Japanese]. Rinsho Iyaku 1993; 9 Suppl. 1: 31–51Google Scholar
- 133.Mikawa H, Baba M. Efficacy and safety of a leukotriene antagonist; ONO-1078 dry syrup, on pediatrie bronchial asthma-dose finding study in a multi-center, open trial [in Japanese]. Rinsho Iyaku 1997; 13(2): 395–421Google Scholar
- 136.Miyamoto T. Activity of pranlukast in asthma and allergic rhinitis [abstract]. Allergy 1996; 51 Suppl. 30: 116Google Scholar
- 137.Miyamoto T, Makino S, Kitamura S, et al. Cysteinyl leukotriene receptor 1 antagonist; MK-476, on adult bronchial asthma in multi-center comparative double-blind clinical study with pranlukast hydrate [in Japanese]. Rinsho Iyaku 2001; 17: 519–58Google Scholar
- 138.Kishimoto T, Okahara M, Chikamori K. Effectiveness of pranlukast for asthmatics [in Japanese]. Jpn J Chest Dis 1998: 57(11): 899–906Google Scholar
- 139.Nagano H, Hirose T, Yoshida M, et al. Clinical experience with long-term use of leukotriene antagonist, ONO-1078, in adult bronchial asthma [in Japanese]. Rinsho Iyaku 1993; 9 Suppl. 1: 185–207Google Scholar
- 140.Satake T, Takagi K, Suzuki R, et al. Study on efficacy and safety of the long-term administration of a leukotriene C4, D4 and E4 antagonist, ONO-1078, on adult bronchial asthma [in Japanese]. Rinsho Iyaku 1993; 9 Suppl. 1: 159–84Google Scholar
- 142.Chiu C-P, Huang J-L, Lin T-Y, et al. Double-blind placebo-controlled study of oxatomide in the treatment of childhood asthma. Acta Paed Sin 1997 Jan 28; 38(1): 14–20Google Scholar
- 143.Marone G, Granata F, Spadaro G, et al. Anti-inflammatory effects of oxatomide. Invest Allergol Clin Immunol 1999 Jul 31; 9(4): 207–14Google Scholar
- 145.Fujino S, Sato K, Imai H, et al. Cost effectiveness analysis of pranlukast (selective leukotriene C4, D4, E4 antagonist) in bronchial asthma therapy [in Japanese]. Rinsho Iyaku 1995; 11(11): 2303–23Google Scholar
- 146.Fujita K, Kohrogi H, Hirata N, et al. The economic impact of long-term therapy by leukotriene antagonist in asthma in Japan [abstract]. Am J Respir Crit Care Med 2001 Apr; 163 Suppl. Pt 2: A430Google Scholar
- 147.The Japan Pharmaceutical Manufacturers Association. Japan Pharmaceutical Reference: Onon dry syrup [online]. Available from URL: http://www.jpma.or.jp/jpr/ [Accessed 2002 Oct 29]
- 150.Wechsler ME, Drazen JM. Leukotriene modifiers and Churg-Strauss syndrome: an update. Am J Respir Crit Care Med 2000 Mar; 161 Suppl. Pt 2: 195Google Scholar
- 153.Kuwahara H, Arimoto T, Hara H. A case of pranlukast-induced Churg-Strauss syndrome [in Japanese]. Jpn J Chest Dis 2001: 60(11): 1041–5Google Scholar
- 159.PLM Latina. Azlaire granulado [online]. Available from URL: http://www.plmlatina.com/sp/sp_alz_cap.htm [Accessed 2002 Dec 19]
- 160.JCN Newswire. Ono announces Schering-Plough launched leukotriene antagonist pranlukast in Mexico [online]. Available from URL: http://www.japancorp.net/Article.Asp?Art_ID=3641 [Accessed 2002 Oct 11]
- 161.British Thoracic Society. Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. Thorax 2003; 58 Suppl. 1: 1–94Google Scholar
- 171.Laitinen LA, Naya IP, Binks S, et al. Comparative efficacy of zafirlukast and low dose steroids in asthmatics on prn β2-agonists [abstract no. 2716]. Eur Respir J 1997; 10 Suppl. 25: 419SGoogle Scholar
- 174.Fujimura M, Tachibana H, Myou S. Comparison between effects of leukotriene and thromboxane A2 antagonist in asthma: a preliminary trial [abstract]. Eur Respir J 2000 Aug; 16 Suppl. 31: 522Google Scholar