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Duncan F Rogers - One of the best experts on this subject based on the ideXlab platform.
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effects of the cysteinyl leukotriene receptor antagonists Pranlukast and zafirlukast on tracheal mucus secretion in ovalbumin sensitized guinea pigs in vitro
British Journal of Pharmacology, 1998Co-Authors: Yuchih Liu, Aamir M Khawaja, Duncan F RogersAbstract:1. We investigated the inhibitory effects of the cysteinyl leukotriene (CysLT1) receptor antagonists, Pranlukast and zafirlukast, on 35SO4 labelled mucus output, in vitro, in guinea-pig trachea, induced by leukotriene D4 (LTD4) or by antigen challenge of sensitized animals. Agonists and antagonists were administered mucosally, except in selected comparative experiments where drugs were administered both mucosally and serosally to assess the influence of the epithelium on evoked-secretion. 2. LTD4 increased 35SO4 output in a concentration-related manner with a maximal increase of 23 fold above controls at 100 microM and an approximate EC50 of 2 microM. Combined mucosal and serosal addition of LTD4 did not significantly affect the secretory response compared with mucosal addition alone. Neither LTC4 nor LTE4 (10 microM each) affected 35SO4 output. Pranlukast or zafirlukast significantly inhibited 10 microM LTD4-evoked 35SO4 output in a concentration-dependent fashion, with maximal inhibitions of 83% at 10 microM Pranlukast and 78% at 10 microM zafirlukast, and IC50 values of 0.3 microM for Pranlukast and 0.6 microM for zafirlukast. Combined mucosal and serosal administration of the antagonists (5 microM each) gave degrees of inhibition of mucosal-serosal 10 microM LTD4-evoked 35SO4 output similar to those of the drugs given mucosally. Pranlukast (0.5 microM) caused a parallel rightward shift of the LTD4 concentration-response curve with a pKB of 7. Pranlukast did not inhibit ATP-induced 35SO4 output. 3. Ovalbumin (10-500 microg ml(-1) challenge of tracheae from guinea-pigs actively sensitized with ovalbumin caused a concentration-related increase in 35SO4 output with a maximal increase of 20 fold above vehicle controls at 200 microg ml(-1). The combination of the antihistamines pyrilamine and cimetidine (0.1 mM each) did not inhibit ovalbumin-induced 35SO4 output in sensitized guinea-pigs. Neither mucosal (10 microM or 100 microM) nor mucosal-serosal (100 microM) histamine had any significant effect on 35SO4 output. 4. Pranlukast or zafirlukast (5 microM each) significantly suppressed ovalbumin-induced secretion in tracheae from sensitized guinea-pigs by 70% and 65%, respectively. 5 We conclude that LTD4 or ovalbumin challenge of sensitized animals provokes mucus secretion from guinea-pig trachea in vitro and this effect is inhibited by the CysLT1 receptor antagonists Pranlukast and zafirlukast. These antagonists may be beneficial in the treatment of allergic airway diseases in which mucus hypersecretion is a clinical symptom, for example asthma and allergic rhinitis.
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Effects of the cysteinyl leukotriene receptor antagonists Pranlukast and zafirlukast on tracheal mucus secretion in ovalbumin‐sensitized guinea‐pigs in vitro
British journal of pharmacology, 1998Co-Authors: Yuchih Liu, Aamir M Khawaja, Duncan F RogersAbstract:1. We investigated the inhibitory effects of the cysteinyl leukotriene (CysLT1) receptor antagonists, Pranlukast and zafirlukast, on 35SO4 labelled mucus output, in vitro, in guinea-pig trachea, induced by leukotriene D4 (LTD4) or by antigen challenge of sensitized animals. Agonists and antagonists were administered mucosally, except in selected comparative experiments where drugs were administered both mucosally and serosally to assess the influence of the epithelium on evoked-secretion. 2. LTD4 increased 35SO4 output in a concentration-related manner with a maximal increase of 23 fold above controls at 100 microM and an approximate EC50 of 2 microM. Combined mucosal and serosal addition of LTD4 did not significantly affect the secretory response compared with mucosal addition alone. Neither LTC4 nor LTE4 (10 microM each) affected 35SO4 output. Pranlukast or zafirlukast significantly inhibited 10 microM LTD4-evoked 35SO4 output in a concentration-dependent fashion, with maximal inhibitions of 83% at 10 microM Pranlukast and 78% at 10 microM zafirlukast, and IC50 values of 0.3 microM for Pranlukast and 0.6 microM for zafirlukast. Combined mucosal and serosal administration of the antagonists (5 microM each) gave degrees of inhibition of mucosal-serosal 10 microM LTD4-evoked 35SO4 output similar to those of the drugs given mucosally. Pranlukast (0.5 microM) caused a parallel rightward shift of the LTD4 concentration-response curve with a pKB of 7. Pranlukast did not inhibit ATP-induced 35SO4 output. 3. Ovalbumin (10-500 microg ml(-1) challenge of tracheae from guinea-pigs actively sensitized with ovalbumin caused a concentration-related increase in 35SO4 output with a maximal increase of 20 fold above vehicle controls at 200 microg ml(-1). The combination of the antihistamines pyrilamine and cimetidine (0.1 mM each) did not inhibit ovalbumin-induced 35SO4 output in sensitized guinea-pigs. Neither mucosal (10 microM or 100 microM) nor mucosal-serosal (100 microM) histamine had any significant effect on 35SO4 output. 4. Pranlukast or zafirlukast (5 microM each) significantly suppressed ovalbumin-induced secretion in tracheae from sensitized guinea-pigs by 70% and 65%, respectively. 5 We conclude that LTD4 or ovalbumin challenge of sensitized animals provokes mucus secretion from guinea-pig trachea in vitro and this effect is inhibited by the CysLT1 receptor antagonists Pranlukast and zafirlukast. These antagonists may be beneficial in the treatment of allergic airway diseases in which mucus hypersecretion is a clinical symptom, for example asthma and allergic rhinitis.
Yuchih Liu - One of the best experts on this subject based on the ideXlab platform.
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effects of the cysteinyl leukotriene receptor antagonists Pranlukast and zafirlukast on tracheal mucus secretion in ovalbumin sensitized guinea pigs in vitro
British Journal of Pharmacology, 1998Co-Authors: Yuchih Liu, Aamir M Khawaja, Duncan F RogersAbstract:1. We investigated the inhibitory effects of the cysteinyl leukotriene (CysLT1) receptor antagonists, Pranlukast and zafirlukast, on 35SO4 labelled mucus output, in vitro, in guinea-pig trachea, induced by leukotriene D4 (LTD4) or by antigen challenge of sensitized animals. Agonists and antagonists were administered mucosally, except in selected comparative experiments where drugs were administered both mucosally and serosally to assess the influence of the epithelium on evoked-secretion. 2. LTD4 increased 35SO4 output in a concentration-related manner with a maximal increase of 23 fold above controls at 100 microM and an approximate EC50 of 2 microM. Combined mucosal and serosal addition of LTD4 did not significantly affect the secretory response compared with mucosal addition alone. Neither LTC4 nor LTE4 (10 microM each) affected 35SO4 output. Pranlukast or zafirlukast significantly inhibited 10 microM LTD4-evoked 35SO4 output in a concentration-dependent fashion, with maximal inhibitions of 83% at 10 microM Pranlukast and 78% at 10 microM zafirlukast, and IC50 values of 0.3 microM for Pranlukast and 0.6 microM for zafirlukast. Combined mucosal and serosal administration of the antagonists (5 microM each) gave degrees of inhibition of mucosal-serosal 10 microM LTD4-evoked 35SO4 output similar to those of the drugs given mucosally. Pranlukast (0.5 microM) caused a parallel rightward shift of the LTD4 concentration-response curve with a pKB of 7. Pranlukast did not inhibit ATP-induced 35SO4 output. 3. Ovalbumin (10-500 microg ml(-1) challenge of tracheae from guinea-pigs actively sensitized with ovalbumin caused a concentration-related increase in 35SO4 output with a maximal increase of 20 fold above vehicle controls at 200 microg ml(-1). The combination of the antihistamines pyrilamine and cimetidine (0.1 mM each) did not inhibit ovalbumin-induced 35SO4 output in sensitized guinea-pigs. Neither mucosal (10 microM or 100 microM) nor mucosal-serosal (100 microM) histamine had any significant effect on 35SO4 output. 4. Pranlukast or zafirlukast (5 microM each) significantly suppressed ovalbumin-induced secretion in tracheae from sensitized guinea-pigs by 70% and 65%, respectively. 5 We conclude that LTD4 or ovalbumin challenge of sensitized animals provokes mucus secretion from guinea-pig trachea in vitro and this effect is inhibited by the CysLT1 receptor antagonists Pranlukast and zafirlukast. These antagonists may be beneficial in the treatment of allergic airway diseases in which mucus hypersecretion is a clinical symptom, for example asthma and allergic rhinitis.
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Effects of the cysteinyl leukotriene receptor antagonists Pranlukast and zafirlukast on tracheal mucus secretion in ovalbumin‐sensitized guinea‐pigs in vitro
British journal of pharmacology, 1998Co-Authors: Yuchih Liu, Aamir M Khawaja, Duncan F RogersAbstract:1. We investigated the inhibitory effects of the cysteinyl leukotriene (CysLT1) receptor antagonists, Pranlukast and zafirlukast, on 35SO4 labelled mucus output, in vitro, in guinea-pig trachea, induced by leukotriene D4 (LTD4) or by antigen challenge of sensitized animals. Agonists and antagonists were administered mucosally, except in selected comparative experiments where drugs were administered both mucosally and serosally to assess the influence of the epithelium on evoked-secretion. 2. LTD4 increased 35SO4 output in a concentration-related manner with a maximal increase of 23 fold above controls at 100 microM and an approximate EC50 of 2 microM. Combined mucosal and serosal addition of LTD4 did not significantly affect the secretory response compared with mucosal addition alone. Neither LTC4 nor LTE4 (10 microM each) affected 35SO4 output. Pranlukast or zafirlukast significantly inhibited 10 microM LTD4-evoked 35SO4 output in a concentration-dependent fashion, with maximal inhibitions of 83% at 10 microM Pranlukast and 78% at 10 microM zafirlukast, and IC50 values of 0.3 microM for Pranlukast and 0.6 microM for zafirlukast. Combined mucosal and serosal administration of the antagonists (5 microM each) gave degrees of inhibition of mucosal-serosal 10 microM LTD4-evoked 35SO4 output similar to those of the drugs given mucosally. Pranlukast (0.5 microM) caused a parallel rightward shift of the LTD4 concentration-response curve with a pKB of 7. Pranlukast did not inhibit ATP-induced 35SO4 output. 3. Ovalbumin (10-500 microg ml(-1) challenge of tracheae from guinea-pigs actively sensitized with ovalbumin caused a concentration-related increase in 35SO4 output with a maximal increase of 20 fold above vehicle controls at 200 microg ml(-1). The combination of the antihistamines pyrilamine and cimetidine (0.1 mM each) did not inhibit ovalbumin-induced 35SO4 output in sensitized guinea-pigs. Neither mucosal (10 microM or 100 microM) nor mucosal-serosal (100 microM) histamine had any significant effect on 35SO4 output. 4. Pranlukast or zafirlukast (5 microM each) significantly suppressed ovalbumin-induced secretion in tracheae from sensitized guinea-pigs by 70% and 65%, respectively. 5 We conclude that LTD4 or ovalbumin challenge of sensitized animals provokes mucus secretion from guinea-pig trachea in vitro and this effect is inhibited by the CysLT1 receptor antagonists Pranlukast and zafirlukast. These antagonists may be beneficial in the treatment of allergic airway diseases in which mucus hypersecretion is a clinical symptom, for example asthma and allergic rhinitis.
Aamir M Khawaja - One of the best experts on this subject based on the ideXlab platform.
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effects of the cysteinyl leukotriene receptor antagonists Pranlukast and zafirlukast on tracheal mucus secretion in ovalbumin sensitized guinea pigs in vitro
British Journal of Pharmacology, 1998Co-Authors: Yuchih Liu, Aamir M Khawaja, Duncan F RogersAbstract:1. We investigated the inhibitory effects of the cysteinyl leukotriene (CysLT1) receptor antagonists, Pranlukast and zafirlukast, on 35SO4 labelled mucus output, in vitro, in guinea-pig trachea, induced by leukotriene D4 (LTD4) or by antigen challenge of sensitized animals. Agonists and antagonists were administered mucosally, except in selected comparative experiments where drugs were administered both mucosally and serosally to assess the influence of the epithelium on evoked-secretion. 2. LTD4 increased 35SO4 output in a concentration-related manner with a maximal increase of 23 fold above controls at 100 microM and an approximate EC50 of 2 microM. Combined mucosal and serosal addition of LTD4 did not significantly affect the secretory response compared with mucosal addition alone. Neither LTC4 nor LTE4 (10 microM each) affected 35SO4 output. Pranlukast or zafirlukast significantly inhibited 10 microM LTD4-evoked 35SO4 output in a concentration-dependent fashion, with maximal inhibitions of 83% at 10 microM Pranlukast and 78% at 10 microM zafirlukast, and IC50 values of 0.3 microM for Pranlukast and 0.6 microM for zafirlukast. Combined mucosal and serosal administration of the antagonists (5 microM each) gave degrees of inhibition of mucosal-serosal 10 microM LTD4-evoked 35SO4 output similar to those of the drugs given mucosally. Pranlukast (0.5 microM) caused a parallel rightward shift of the LTD4 concentration-response curve with a pKB of 7. Pranlukast did not inhibit ATP-induced 35SO4 output. 3. Ovalbumin (10-500 microg ml(-1) challenge of tracheae from guinea-pigs actively sensitized with ovalbumin caused a concentration-related increase in 35SO4 output with a maximal increase of 20 fold above vehicle controls at 200 microg ml(-1). The combination of the antihistamines pyrilamine and cimetidine (0.1 mM each) did not inhibit ovalbumin-induced 35SO4 output in sensitized guinea-pigs. Neither mucosal (10 microM or 100 microM) nor mucosal-serosal (100 microM) histamine had any significant effect on 35SO4 output. 4. Pranlukast or zafirlukast (5 microM each) significantly suppressed ovalbumin-induced secretion in tracheae from sensitized guinea-pigs by 70% and 65%, respectively. 5 We conclude that LTD4 or ovalbumin challenge of sensitized animals provokes mucus secretion from guinea-pig trachea in vitro and this effect is inhibited by the CysLT1 receptor antagonists Pranlukast and zafirlukast. These antagonists may be beneficial in the treatment of allergic airway diseases in which mucus hypersecretion is a clinical symptom, for example asthma and allergic rhinitis.
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Effects of the cysteinyl leukotriene receptor antagonists Pranlukast and zafirlukast on tracheal mucus secretion in ovalbumin‐sensitized guinea‐pigs in vitro
British journal of pharmacology, 1998Co-Authors: Yuchih Liu, Aamir M Khawaja, Duncan F RogersAbstract:1. We investigated the inhibitory effects of the cysteinyl leukotriene (CysLT1) receptor antagonists, Pranlukast and zafirlukast, on 35SO4 labelled mucus output, in vitro, in guinea-pig trachea, induced by leukotriene D4 (LTD4) or by antigen challenge of sensitized animals. Agonists and antagonists were administered mucosally, except in selected comparative experiments where drugs were administered both mucosally and serosally to assess the influence of the epithelium on evoked-secretion. 2. LTD4 increased 35SO4 output in a concentration-related manner with a maximal increase of 23 fold above controls at 100 microM and an approximate EC50 of 2 microM. Combined mucosal and serosal addition of LTD4 did not significantly affect the secretory response compared with mucosal addition alone. Neither LTC4 nor LTE4 (10 microM each) affected 35SO4 output. Pranlukast or zafirlukast significantly inhibited 10 microM LTD4-evoked 35SO4 output in a concentration-dependent fashion, with maximal inhibitions of 83% at 10 microM Pranlukast and 78% at 10 microM zafirlukast, and IC50 values of 0.3 microM for Pranlukast and 0.6 microM for zafirlukast. Combined mucosal and serosal administration of the antagonists (5 microM each) gave degrees of inhibition of mucosal-serosal 10 microM LTD4-evoked 35SO4 output similar to those of the drugs given mucosally. Pranlukast (0.5 microM) caused a parallel rightward shift of the LTD4 concentration-response curve with a pKB of 7. Pranlukast did not inhibit ATP-induced 35SO4 output. 3. Ovalbumin (10-500 microg ml(-1) challenge of tracheae from guinea-pigs actively sensitized with ovalbumin caused a concentration-related increase in 35SO4 output with a maximal increase of 20 fold above vehicle controls at 200 microg ml(-1). The combination of the antihistamines pyrilamine and cimetidine (0.1 mM each) did not inhibit ovalbumin-induced 35SO4 output in sensitized guinea-pigs. Neither mucosal (10 microM or 100 microM) nor mucosal-serosal (100 microM) histamine had any significant effect on 35SO4 output. 4. Pranlukast or zafirlukast (5 microM each) significantly suppressed ovalbumin-induced secretion in tracheae from sensitized guinea-pigs by 70% and 65%, respectively. 5 We conclude that LTD4 or ovalbumin challenge of sensitized animals provokes mucus secretion from guinea-pig trachea in vitro and this effect is inhibited by the CysLT1 receptor antagonists Pranlukast and zafirlukast. These antagonists may be beneficial in the treatment of allergic airway diseases in which mucus hypersecretion is a clinical symptom, for example asthma and allergic rhinitis.
Kian Fan Chung - One of the best experts on this subject based on the ideXlab platform.
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Leukotriene antagonists and Churg-Strauss syndrome: the smoking gun
Thorax, 1999Co-Authors: R G Stirling, Kian Fan ChungAbstract:The cysteinyl leukotrienes, leukotriene C4 (LTC4), LTD4, and LTE4 are pro-inflammatory agents previously known as the “slow reacting substances of anaphylaxis”. These arachidonic acid derivatives have broad ranging pro-inflammatory actions including airway smooth muscle contraction and bronchoconstriction, increase in vascular permeability, increase in mucus secretion, and inflammatory cell infiltration of lung tissue.1 The leukotriene receptor antagonists (LTRAs) zafirlukast, Pranlukast, and montelukast block the effects of these mediators and are the most recently released agents with potential anti-inflammatory action for use in asthma.2 They are antagonists of LTC4, LTD4, and LTE4 and act as selective competitive antagonists of the cysteinyl leukotriene (CysLT1) receptor, as distinct from the 5-lipoxygenase inhibitor zileuton. An association between LTRAs and Churg-Strauss syndrome (CSS) has recently been suggested by a series of published case reports. CSS is a rare systemic vasculitis whose characteristic features include extravascular eosinophil infiltration/vasculitis, peripheral eosinophilia, and asthma. The case reports published to date describe 15 subjects, 13 of whom were being treated with zafirlukast3-7 and one with Pranlukast8; a single case of pulmonary eosinophilia following treatment with montelukast9 has also been reported although this case may reasonably be reclassified as CSS. The Medicines Control Agency (UK) has received five reports of CSS associated with the use of montelukast and notes 35 such …
Min-soo Kim - One of the best experts on this subject based on the ideXlab platform.
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Determination and correlation of solubility of Pranlukast hemihydrate in five organic solvents at different temperatures and its dissolution properties
Journal of Molecular Liquids, 2017Co-Authors: Jeong-soo Kim, In-hwan Baek, Do-hoon Kuk, Min-soo KimAbstract:Abstract In this study, the solubility of Pranlukast hemihydrate in methanol, ethanol, 1-propanol, 2-propanol, and 1-butanol was determined at temperatures ranging from 298.15 to 323.15 K by a solid-liquid equilibrium method. The measured solubility data of Pranlukast hemihydrate were correlated with the modified Apelblat and Van't Hoff models. The maximum mole fraction solubility of Pranlukast hemihydrate in 1-butanol was observed to be 26.39 × 10 − 5 at 323.15 K, followed by that in 1-propanol (9.63 × 10 − 5 at 323.15 K), ethanol (6.18 × 10 − 5 at 323.15 K), 2-propanol (5.71 × 10 − 5 at 323.15 K), and methanol (3.96 × 10 − 5 at 323.15 K). Interestingly, the solubility of Pranlukast hemihydrate increases with a decrease in dielectric constant of the primary alcohols. The measured solubility data of Pranlukast hemihydrate correlated well with the modified Apelblat equation. In addition, thermodynamic analysis indicated an endothermic and spontaneous dissolution behavior of Pranlukast hemihydrate in the studied solvents. Therefore, these experimental solubilities and correlation equations can be useful in the purification/crystallization and formulation study of Pranlukast hemihydrate in laboratories and related industries.
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improving dissolution and oral bioavailability of Pranlukast hemihydrate by particle surface modification with surfactants and homogenization
Drug design development and therapy, 2015Co-Authors: In-hwan Baek, Jin-wook Yoo, Yunjin Jung, Min-soo KimAbstract:The present study was carried out to develop an oral formulation of Pranlukast hemihydrate with improved dissolution and oral bioavailability using a surface-modified microparticle. Based on solubility measurements, surface-modified Pranlukast hemihydrate microparticles were manufactured using the spray-drying method with hydroxypropylmethyl cellulose, sucrose laurate, and water and without the use of an organic solvent. The hydrophilicity of the surface-modified Pranlukast hemihydrate microparticle increased, leading to enhanced dissolution and oral bioavailability of Pranlukast hemihydrate without a change in crystallinity. The surface-modified microparticles with an hydroxypropylmethyl cellulose/sucrose laurate ratio of 1:2 showed rapid dissolution of up to 85% within 30 minutes in dissolution medium (pH 6.8) and oral bioavailability higher than that of the commercial product, with approximately 2.5-fold and 3.9-fold increases in area under the curve (AUC0→12 h) and peak plasma concentration, respectively. Therefore, the surface-modified microparticle is an effective oral drug delivery system for the poorly water-soluble therapeutic Pranlukast hemihydrate.