Cysteinyl Leukotrienes Induce Nasal Symptoms of Allergic Rhinitis via a Receptor-Mediated Mechanism in Guinea Pigs

Fujita, Manabu; Nakagawa, Naoki; Yonetomi, Yasuo; Takeda, Hiroshi; Kawabata, Kazuhito; Ohno, Hiroyuki

doi:10.1254/jjp.75.355

Cited by 19 publications

(13 citation statements)

References 19 publications

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“…In addition, CysLTs mimic some manifestations of asthma and rhinitis [41][42]. Finally, the beneficial effect of leukotriene receptor antagonists can be regarded as an indication of the role of CysLTs in these processes [43][44].…”

Section: Leukotrienes In Allergic Diseasesmentioning

confidence: 99%

Arachidonic Acid Signaling in Pathogenesis of Allergy: Therapeutic Implications

Serrano-Mollar¹,

Closa

2005

CDTIA

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Section: Leukotrienes In Allergic Diseasesmentioning

confidence: 99%

Arachidonic Acid Signaling in Pathogenesis of Allergy: Therapeutic Implications

Serrano-Mollar¹,

Closa

2005

CDTIA

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“…[1][2][3] The proportional of pediatric patients with allergic rhinitis is assumed to be approximately 30z out of 18 to 23 million patients estimated in Japan. The main symptoms of allergic rhinitis include sneezing, nasal discharge, and nasal congestion.…”

Section: Introductionmentioning

confidence: 99%

Population Pharmacokinetics of Pranlukast Hydrate Dry Syrup in Children with Allergic Rhinitis and Bronchial Asthma

Nakade¹,

Ueda²,

Ohno³

et al. 2006

Drug Metabolism and Pharmacokinetics

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This study aimed to assess the steady-state pharmacokinetics of pranlukast, a leukotriene receptor antagonist, in children with allergic rhinitis and bronchial asthma, and to clarify factors affecting apparent clearance (CL/F). A total of 192 plasma samples were obtained from 98 children (rhinitis 64, asthma 13, complications 21), aged 3-14 years in 2 clinical trials. Plasma concentration of pranlukast was determined by liquid chromatography connected with a tandem mass spectrometer and analyzed by a population approach using NONMEM program. The plasma concentration-time course of pranlukast was described by using a one-compartment model with the first-order absorption and lag time. The robustness of the population pharmacokinetic model was evaluated by using 200 bootstrap samples. The results of population pharmacokinetic analysis showed that only age was a factor affecting the CL/F per body weight, with CL/F decreasing with increasing age. No significant variation was seen in the CL/F between rhinitis and asthma. The interindividual variability in the CL/F and the residual variability were 19.7% and 48.4%, respectively. All the parameters fell within 10% of the bootstrapped mean. In conclusion, the results show that age is the most influential factor for explaining interindividual variability in CL/F, and the difference in diseases does not affect CL/F.

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“…[1][2][3] Pranlukast is a selective cysLTs receptor antagonist, and a 225 mg twice-daily dose has been used to treat bronchial asthma and allergic rhinitis in Japan.The absorption fraction of pranlukast in human is approximately 20%, based on the excretion ratio of the unchanged form in the feces following oral administration (the absolute bioavailability has not been reported). The terminal elimination half-life of pranlukast in plasma is approximately 2 h. Pranlukast is minimally excreted in the urine.…”

mentioning

confidence: 99%

In Vitro Metabolism and Inhibitory Effects of Pranlukast in Human Liver Microsomes

Yoneda

Matsumoto

Sutoh

et al. 2009

Biological & Pharmaceutical Bulletin

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Cysteinyl leukotrienes (cysLTs) are 5-lipoxygenase pathway products of arachidonate that induce bronchoconstriction, vascular hyperpermeability, mucosal edema accumulation, and mucus secretion. [1][2][3] Pranlukast is a selective cysLTs receptor antagonist, and a 225 mg twice-daily dose has been used to treat bronchial asthma and allergic rhinitis in Japan.The absorption fraction of pranlukast in human is approximately 20%, based on the excretion ratio of the unchanged form in the feces following oral administration (the absolute bioavailability has not been reported). The terminal elimination half-life of pranlukast in plasma is approximately 2 h. Pranlukast is minimally excreted in the urine. The major metabolic pathway of pranlukast is shown in Fig. 1. The plasma-binding of pranlukast is more than 99%, and the major binding protein is albumin.To date, it has been very difficult to predict drug-drug interactions with pranlukast in the clinical setting due to a lack of information. Therefore, we conducted in vitro experiments using human liver microsomes to allow us to evaluate the potential for drug-drug interactions, based on the metabolism and the inhibitory effects of pranlukast. MATERIALS AND METHODS MaterialsPranlukast and 6-methyl-4-oxo-8-[4-(4-phenylbutoxy)benzoylamino]-2-(tetrazol-5-yl)-4H-1-benzopyran (ONO-RS-425, an internal standard for pranlukast), were synthesized at Ono Pharmaceutical Co., Ltd. (Osaka, Japan). a-Naphthoflavone, quinideine, 4-hydroxybenzoic acid n-butyl ester and 4-hydroxybenzoic acid n-amyl ester were purchased from Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan). Tranylcypromine, terfenadine, metoprolol, tolbutamide, erythromycin and roxithromycin were pur- We investigated the metabolism of pranlukast, a selective leukotriene agonist, and the potential for drugdrug interactions. Although cytochrome P450 (CYP) 3A4 appeared to be the major cytochrome P450 isoform involved in the metabolism of pranlukast, the results suggested that pranlukast metabolism was inhibited less than 50% by ketoconazole, a reversible CYP3A4 inhibitor, or by anti-CYP3A4 antibodies. Irreversible macrolide CYP3A4 inhibitors, clarithromycin, erythromycin and roxithromycin, exhibited little effect on pranlukast metabolism. On the other hand, pranlukast reversibly inhibited CYP2C8 and/or 2C9, and CYP3A4, with K i values of 3.9 and 4.1 m mmol/l, respectively. The [I] in,max,u /K i ratios were 0.004 and 0.003, respectively. The K i values were about 300-fold greater than the [I] in,max,u , therefore it is suggested that, at clinical doses, pranlukast will not affect the pharmacokinetics of concomitantly administered drugs that are primarily metabolized by CYP2C8 and/or 2C9 or CYP3A4.

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Cysteinyl Leukotrienes Induce Nasal Symptoms of Allergic Rhinitis via a Receptor-Mediated Mechanism in Guinea Pigs

Cited by 19 publications

References 19 publications

Arachidonic Acid Signaling in Pathogenesis of Allergy: Therapeutic Implications

Arachidonic Acid Signaling in Pathogenesis of Allergy: Therapeutic Implications

Population Pharmacokinetics of Pranlukast Hydrate Dry Syrup in Children with Allergic Rhinitis and Bronchial Asthma

In Vitro Metabolism and Inhibitory Effects of Pranlukast in Human Liver Microsomes

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