The position of pranlukast, a cysteinyl leukotriene receptor antagonist, in the long-term treatment of asthma. 5-year follow-up study.

BACKGROUND: Adverse effects, tachyphylaxis, and the position of pranlukast, a cysteinyl leukotriene receptor antagonist, in asthma treatment have not been fully established. OBJECTIVES AND METHODS: To address these questions, adverse effects and long-term efficacy of pranlukast were evaluated in 82 patients [28 patients with moderate asthma (group I), 27 with severe persistent asthma not on oral corticosteroid (OCS; group II) and 27 with severe persistent asthma on OCS (group III)] at 4 and 16 weeks. In the following, pranlukast was either withdrawn 1 year after the start of therapy, or if that was not possible due to reappearance of symptoms, the dose of OCS or inhaled corticosteroid (ICS) was reduced. The efficacy of pranlukast was evaluated during 5 years by peak expiratory flow rate (PEFR), and symptom and treatment scores. RESULTS: Adverse reactions appeared in 4 patients (4.9%; diarrhea, dizziness and leg edema). The mean improvement in PEFR on week 16 was 18.5 +/- 2.3, 18.8 +/- 3.2, and 15.2 +/- 3.8% in groups I-III, respectively (p < 0.01, for all groups). However, increases in PEFR in 29 of 72 patients (40.3%) were less than 15%. Pranlukast could not be withdrawn in 28 of 42 responders (66.7%), but their dose of ICS was reduced by 363 +/- 97 microg/day (group II) and that of OCS by 3.4 +/- 0.7 mg/day (group III). Tachyphylaxis was not recognized during the 5-year period. CONCLUSION: Pranlukast is safe when taken for up to 5 years, and is effective irrespective of asthma severity. In the majority of patients with persistent asthma, pranlukast may help to control the disease in the long term.

Polymorphisms in the CYP1A2 gene and theophylline metabolism in patients with asthma.

BACKGROUND: Cytochrome p450 (CYP) 1A2 gene polymorphisms are thought to be involved in theophylline metabolism. OBJECTIVE: We analyzed the effect of genetic polymorphisms in the 5'-flanking region to the first intron of the CYP1A2 gene on theophylline metabolism in 75 Japanese patients with asthma and 159 healthy Japanese volunteers. METHODS: Genetic polymorphisms were detected at 4 sites of the CYP1A2 gene, -2964(G/A) and -1569(T/del) in the 5'-flanking region and 155(T/G) and 731(A/C) in the first intron. RESULTS: There were no significant differences in the distribution of gene polymorphisms between the asthmatic and control groups. Among asthmatic patients, theophylline clearance was significantly lower in patients with the polymorphism at site -2964(G/A) whose genotype was G/A (0.029 +/- 0.001 L x h(-1) x kg(-1)) or A/A (0.029 +/- 0.002 L x h(-1) x kg(-1)) than in those whose genotype was G/G (0.034 +/- 0.001 L x h(-1) x kg(-1)) (P <.01 and P <.05, respectively). High theophylline clearance levels significantly correlated with age in the G/G subgroup of site -2964(G/A) (P <.05, r = -0.35) but not in the G/A or A/A subgroup. CONCLUSION: Given its potential side effects, theophylline may need to be used with care in patients with the A allele at site -2964(G/A) in the CYP1A2 gene, because theophylline metabolism levels are lower in such patients, particularly in young asthmatic individuals.