Pranlukast

Pranlukast

Efficacy and Safety of Modified Pranlukast (Prakanon((R))) Compared with Pranlukast (Onon((R))): A Randomized, Open-Label, Crossover Study.[Pubmed:27499820]

Open Respir Med J. 2016 Jun 30;10:36-45.

INTRODUCTION: Pranlukast is a leukotriene receptor antagonist (LTRA) that is used as an additional controller of mild to moderate asthma. This study compared the efficacy and side effects of two bioequivalent preparations of Pranlukast: original Pranlukast (Onon((R)); Ono Pharmaceutical, Japan) and a modified formulation of Pranlukast (Prakanon((R)); Yuhan Co, Korea) in patients with mild to moderate asthma. METHODS: Of the 34 subjects screened, 30 patients who were using standard medication to control asthma and scored less than 20 points on the Asthma Control Test() (ACT) were assigned randomly to one of the two groups in a prospective, open label, crossover study: group 1 received Prakanon((R)) (150 mg/day) and group 2 received Onon((R)) (450 mg/day) for 8 weeks each; after a 1-week rest period, the groups were switched to the alternative medication for further 8 weeks and monitored for 2 more weeks without study medication. Evaluation parameters included the ACT, quality of life questionnaire adult Korean asthmatics (QLQAKA), pulmonary function tests, peripheral blood tests, vital signs, and adverse events. RESULTS: Thirty patients were enrolled and 21 completed the trial: 10 in group 1 and 11 in group 2. The baseline data of the two groups did not differ. No statistical significant differences were observed in efficacy and lung function at each time and in changes from baseline value between the two kinds of Pranlukast. The final asthma control rate was 81% with Prakanon((R)) and 76% with Onon((R)). There were no differences in vital signs and laboratory data at each time and in changes from baseline value between the two drugs. There were no differences in adverse events between the two drugs. The most common side effect was abdominal pain. Drug compliance was high, without differences between the two drugs. CONCLUSION: These findings suggest that Prakanon((R)) which is an improved formulation of Pranlukast at a lower dose than the original formulation, Onon((R)), has a similar efficacy and side effect profile in the control of persistent asthma.

Effects of Temperature and Solvent on the Solid-State Transformations of Pranlukast During Mechanical Milling.[Pubmed:28249805]

J Pharm Sci. 2017 Jun;106(6):1680-1687.

Four solid forms of Pranlukast (PRS) were obtained during mechanical milling including neat milling (NM) and solvent-drop milling (SDM), which were characterized by various analytical techniques. The effect of milling conditions including 3 milling temperatures and 6 assist solvents on the solid-state transformations of commercial PRS (PRS HH) was systemically investigated. Milling temperature significantly influenced the NM process. A low milling temperature (5 degrees C) led to a complete amorphization of PRS HH, whereas higher milling temperatures (15 degrees C and 30 degrees C) only induced a partial amorphization. The milling at 5 degrees C was proven to be a progressive amorphization process, and the amorphous material showed an increasing stability with prolonged milling time. Amorphous PRS can stay stable under low temperature and relative humidity conditions and showed significantly higher solubilities and faster dissolution rates in both water and pH 6.8 phosphate buffer solution. A total of 6 solvents were used in the SDM experiments. N,N-dimethylformamide and dimethyl sulfoxide should be avoided in the manufacturing process of PRS because corresponding solvates of PRS can be easily generated by SDM of PRS HH with short milling time and small amount of solvents.

Pranlukast reduces asthma exacerbations during autumn especially in 1- to 5-year-old boys.[Pubmed:28154801]

Asia Pac Allergy. 2017 Jan;7(1):10-18.

BACKGROUND: Leukotriene receptor antagonists have been used to prevent virus-induced asthma exacerbations in autumn. Its efficacy, however, might differ with age and sex. OBJECTIVE: This study aimed to investigate whether Pranlukast added to usual asthma therapy in Japanese children during autumn, season associated with the peak of asthma, reduces asthma exacerbations. It was also evaluated the effect of age and sex on Pranlukast's efficacy. METHODS: A total of 121 asthmatic children aged 1 to 14 years were randomly assigned to receive regular Pranlukast or not according to sex, and were divided in 2 age groups, 1-5 years and 6-14 years. The primary outcome was total asthma score calculated during 8 weeks by using a sticker calendar related to the days in which a child experienced a worsening of asthma symptoms. This open study lasted 60 days from September 15 to November 14, 2007. RESULTS: Significant differences in Pranlukast efficacy were observed between sex and age groups. Boys aged 1 to 5 years had the lower total asthma score at 8 weeks (p = 0.002), and experienced fewer cold episodes (p = 0.007). There were no significant differences between Pranlukast and control group in total asthma score at 8 weeks (p = 0.35), and in the days in which a child experienced a worsening of asthma symptoms (p = 0.67). CONCLUSION: There was a substantial benefit of adding Pranlukast to usual therapy in asthmatic children, especially in boys aged 1 to 5 years, during autumn season.

The effect of the leukotriene antagonist pranlukast on pediatric acute otitis media.[Pubmed:27368439]

Int J Pediatr Otorhinolaryngol. 2016 Aug;87:34-8.

OBJECTIVE: Conventional treatment for acute otitis media mainly targets bacteria with antibiotics, neglecting to control for mediators of inflammation. Mediators of inflammation, such as leukotrienes, have been identified in patients with acute otitis media (AOM) or subsequent secretory otitis media (SOM). They can cause functional eustachian tube dysfunction or increase mucous in the middle ear, causing persistent SOM following AOM. The objective of the present study was to evaluate whether or not administration of Pranlukast, a widely used leukotriene C4, D4, and E4 antagonist, together with antibiotics could inhibit the progression to SOM. METHODS: Children with AOM, who were from two to 12 years old, were randomly divided into two groups as follows: a control group in which 50 patients received antibiotic-based conventional treatment according to guidelines for treating AOM proposed by the Japan Otological Society (version 2006); and a Pranlukast group, in which 52 patients were administered Pranlukast for up to 28 days as well as given conventional treatment. Cases were regarded as persistent SOM when a tympanogram was type B or C2 four weeks after treatment was initiated. RESULTS: Two patients in the Pranlukast group and 3 patients in the control group were excluded because they relapsed AOM within 28 days after initial treatment. Therefore, the analysis included 50 and 47 subjects in the Pranlukast and control groups, respectively. The percentage of patients diagnosed with persistent SOM (22.0%) was significantly smaller in the Pranlukast group compared with the control group (44.7%) (p = 0.018, chi-squared test). CONCLUSION: The results indicate that combined treatment of AOM with antibiotics and a leukotriene antagonist to control inflammation is useful for preventing progression to persistent SOM.

Inhibition of human eosinophil activation by a cysteinyl leukotriene receptor antagonist (pranlukast; ONO-1078).[Pubmed:12870835]

J Asthma. 2003 Jun;40(4):395-404.

Eosinophils produce cysteinyl leukotrienes such as leukotriene C4 and D4 upon stimulation by platelet-activating factor or other mediators, and these cells themselves express cysteinyl leukotriene receptors. Pranlukast, a compound developed in Japan, antagonizes cysteinyl leukotriene receptors and inhibits contraction of airway smooth muscle, microvascular leakage into airways, and eosinophil infiltration. This agent can decrease symptoms of bronchial asthma, but its specific influences on effector functions of eosinophils important to the pathogenesis and exacerbation of asthma remain unknown. In the present study, we investigated the effect of Pranlukast on human eosinophil functions. Eosinophils obtained from peripheral blood of normal volunteers were stimulated by platelet-activating factor, leukotriene D4, or phorbol ester. Superoxide anion generation was measured by reduction of cytochrome c. Expression of alphaMbeta2 was analyzed by flow cytometry. To evaluate eosinophil degranulation, eosinophil protein X, a toxic granule constituent, was measured by radioimmunoassay in sample supernatants. Pranlukast partially inhibited major eosinophil effector functions of superoxide anion generation and degranulation induced by platelet-activating factor, although at concentrations tested Pranlukast failed to significantly reduce platelet-activating factor-induced alphaMbeta2 expression. Pranlukast completely inhibited leukotriene D4-induced superoxide generation and alphaMbeta2 expression. In contrast, Pranlukast at 10(-6)M did not affect phorbol ester-induced superoxide generation at 120 minutes, degranulation, or alphaMbeta2 expression. The results suggested that inhibition by Pranlukast of platelet-activating, factor-induced eosinophil effector functions such as superoxide generation and degranulation might result at least partly from antagonism of autocrine mechanisms involving cysteinyl leukotrienes produced in response to platelet-activating factor.

Characterization of the human cysteinyl leukotriene 2 receptor.[Pubmed:10851239]

J Biol Chem. 2000 Sep 29;275(39):30531-6.

The contractile and inflammatory actions of the cysteinyl leukotrienes (CysLTs), LTC(4), LTD(4), and LTE(4), are thought to be mediated through at least two distinct but related CysLT G protein-coupled receptors. The human CysLT(1) receptor has been recently cloned and characterized. We describe here the cloning and characterization of the second cysteinyl leukotriene receptor, CysLT(2), a 346-amino acid protein with 38% amino acid identity to the CysLT(1) receptor. The recombinant human CysLT(2) receptor was expressed in Xenopus oocytes and HEK293T cells and shown to couple to elevation of intracellular calcium when activated by LTC(4), LTD(4), or LTE(4). Analyses of radiolabeled LTD(4) binding to the recombinant CysLT(2) receptor demonstrated high affinity binding and a rank order of potency for competition of LTC(4) = LTD(4) LTE(4). In contrast to the dual CysLT(1)/CysLT(2) antagonist, BAY u9773, the CysLT(1) receptor-selective antagonists MK-571, montelukast (Singulair(TM)), zafirlukast (Accolate(TM)), and Pranlukast (Onon(TM)) exhibited low potency in competition for LTD(4) binding and as antagonists of CysLT(2) receptor signaling. CysLT(2) receptor mRNA was detected in lung macrophages and airway smooth muscle, cardiac Purkinje cells, adrenal medulla cells, peripheral blood leukocytes, and brain, and the receptor gene was mapped to chromosome 13q14, a region linked to atopic asthma.

Characterization of the human cysteinyl leukotriene CysLT1 receptor.[Pubmed:10391245]

Nature. 1999 Jun 24;399(6738):789-93.

The cysteinyl leukotrienes-leukotriene C4(LTC4), leukotriene D4(LTD4) and leukotriene E4(LTE4)-are important mediators of human bronchial asthma. Pharmacological studies have determined that cysteinyl leukotrienes activate at least two receptors, designated CysLT1 and CysLT2. The CysLT1-selective antagonists, such as montelukast (Singulair), zafirlukast (Accolate) and Pranlukast (Onon), are important in the treatment of asthma. Previous biochemical characterization of CysLT1 antagonists and the CysLT1 receptor has been in membrane preparations from tissues enriched for this receptor. Here we report the molecular and pharmacological characterization of the cloned human CysLT1 receptor. We describe the functional activation (calcium mobilization) of this receptor by LTD4 and LTC4, and competition for radiolabelled LTD4 binding to this receptor by the cysteinyl leukotrienes and three structurally distinct classes of CysLT1-receptor antagonists. We detected CysLT1-receptor messenger RNA in spleen, peripheral blood leukocytes and lung. In normal human lung, expression of the CysLT1-receptor mRNA was confined to smooth muscle cells and tissue macrophages. Finally, we mapped the human CysLT1-receptor gene to the X chromosome.

Pranlukast is a highly potent, selective and competitive antagonist of peptide leukotrienes. Pranlukast inhibits [3H]LTE4, [3H]LTD4, and [3H]LTC4 bindings to lung membranes with Kis of 0.63±0.11, 0.99±0.19, and 5640±680 nM, respectively.

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