Statistical investigation of the full concentration range of fasted and fed simulated intestinal fluid on the equilibrium solubility of oral drugs.
In this study a design of experiment covering the full range from the lower limit of fasted to the upper limit of fed parameters and using a small number of experiments has been performed. The measured equilibrium solubility values are comparable with literature values for simulated fasted and fed intestinal fluids as well as human fasted and fed intestinal fluids. The equilibrium solubility data range is statistically equivalent to a combination of published fasted and fed design of experiment data in six (indomethacin, phenytoin, zafirlukast, carvedilol, fenofibrate and probucol) drugs with three (aprepitant, tadalafil a...
Source: European Journal of Pharmaceutical Sciences - October 5, 2017 Category: Drugs & Pharmacology Authors: Perrier J, Zhou Z, Dunn C, Khadra I, Wilson CG, Halbert G Tags: Eur J Pharm Sci Source Type: research
Effect of composition of simulated intestinal media on the solubility of poorly soluble compounds investigated by design of experiments.
Abstract
The composition of the human intestinal fluids varies both intra- and inter-individually. This will influence the solubility of orally administered drug compounds, and hence, the absorption and efficacy of compounds displaying solubility limited absorption. The purpose of this study was to assess the influence of simulated intestinal fluid (SIF) composition on the solubility of poorly soluble compounds. Using a Design of Experiments (DoE) approach, a set of 24 SIF was defined within the known compositions of human fasted state intestinal fluid. The SIF were composed of phospholipid, bile salt, and...
Source: European Journal of Pharmaceutical Sciences - October 3, 2017 Category: Drugs & Pharmacology Authors: Madsen CM, Feng KI, Leithead A, Canfield N, Jørgensen SA, Müllertz A, Rades T Tags: Eur J Pharm Sci Source Type: research
Cysteinyl Leukotriene Receptor Antagonists Inhibit Migration, Invasion, and Expression of MMP-2/9 in Human Glioblastoma.
Abstract
Glioblastoma is one of the most malignant and aggressive types of brain tumors. 5-lipoxygenase and cysteinyl leukotriene receptor 1 (CysLT1) play a role in human carcinogenesis. Leukotriene receptor antagonists (LTRAs), anti-asthmatic drugs with mild side effects, have anti-metastatic activity in epidermoid carcinoma, lung carcinoma, and colon cancers as well as neuroprotective effects. Herein, anti-migratory effects of two LTRAs, montelukast and zafirlukast, were investigated in glioblastoma cells. The level of CysLT1 in A172 cells was increased by 3.13 folds after IL-1β treatment. The median to...
Source: Cellular and Molecular Neurobiology - June 9, 2017 Category: Cytology Authors: Piromkraipak P, Sangpairoj K, Tirakotai W, Chaithirayanon K, Unchern S, Supavilai P, Power C, Vivithanaporn P Tags: Cell Mol Neurobiol Source Type: research
Probable Montelukast-Induced Hepatotoxicity in a Pediatric Patient: Case Report
To the Editor: Drug-induced liver injury is a potential complication of many medications. Montelukast and zafirlukast are competitive and selective leukotriene-receptor antagonists (LTRA) approved for (Source: Annals of Saudi Medicine)
Source: Annals of Saudi Medicine - May 12, 2017 Category: General Medicine Tags: ISSUE 6 Source Type: research
The leukotriene receptor antagonist montelukast and its possible role in the cardiovascular field
ConclusionsWhat it is known about leukotriene receptor antagonists?•Leukotriene receptor antagonist, such as montelukast and zafirlukast, is used in asthma, COPD, and allergic rhinitis.• Montelukast is the most prescribed CysLT1 antagonist used in asthmatic patients.• Different in vivo animal studies have shown that leukotriene receptor antagonists can prevent the atherosclerosis progression, and have a protective role after cerebral ischemia.What we still need to know?• Today, there is a need for conducting clinical trials to assess the role of montelukast in reducing cardiovascular risk and to further understand ...
Source: European Journal of Clinical Pharmacology - April 4, 2017 Category: Drugs & Pharmacology Source Type: research
Addition of anti-leukotriene agents to inhaled corticosteroids for adults and adolescents with persistent asthma.
CONCLUSIONS: For adolescents and adults with persistent asthma, with suboptimal asthma control with daily use of ICS, the addition of anti-leukotrienes is beneficial for reducing moderate and severe asthma exacerbations and for improving lung function and asthma control compared with the same dose of ICS. We cannot be certain that the addition of anti-leukotrienes is superior, inferior or equivalent to a higher dose of ICS. Scarce available evidence does not support anti-leukotrienes as an ICS sparing agent, and use of LTRAs was not associated with increased risk of withdrawals or adverse effects, with the exception of an ...
Source: Cochrane Database of Systematic Reviews - March 15, 2017 Category: Journals (General) Authors: Chauhan BF, Jeyaraman MM, Singh Mann A, Lys J, Abou-Setta AM, Zarychanski R, Ducharme FM Tags: Cochrane Database Syst Rev Source Type: research
Prophylactic Leukotriene Inhibitor Therapy for the Reduction of Capsular Contracture in Primary Silicone Breast Augmentation: Experience with over 1100 Cases
Conclusions: Accolate therapy used for 3 months postoperatively was associated with significantly lower capsular contracture rates compared with untreated patients at 1-year follow-up (p (Source: Plastic and Reconstructive Surgery)
Source: Plastic and Reconstructive Surgery - February 1, 2017 Category: Cosmetic Surgery Tags: Cosmetic: Original Articles Source Type: research
Statistical investigation of simulated fed intestinal media composition on the equilibrium solubility of oral drugs.
Abstract
Gastrointestinal fluid is a complex milieu and it is recognised that gut drug solubility is different to that observed in simple aqueous buffers. Simulated gastrointestinal media have been developed covering fasted and fed states to facilitate in vitro prediction of gut solubility and product dissolution. However, the combination of bile salts, phospholipids, fatty acids and proteins in an aqueous buffered system creates multiple phases and drug solubility is therefore a complex interaction between these components, which may create unique environments for each API. The impact on solubility can be...
Source: European Journal of Pharmaceutical Sciences - December 6, 2016 Category: Drugs & Pharmacology Authors: Zhou Z, Dunn C, Khadra I, Wilson CG, Halbert GW Tags: Eur J Pharm Sci Source Type: research
Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of zafirlukast.
Abstract
Zafirlukast, a cysteinyl leukotriene receptor antagonist, is indicated for the treatment of patients with mild to moderate asthma. Zafirlukast is metabolized mainly by CYP3A4 and CYP2C9. We investigated the effects of the major CYP2C9 variant alleles in Asian populations, CYP2C9*3 and CYP2C9*13, on the pharmacokinetics of zafirlukast in healthy Korean subjects. A single 20-mg oral dose of zafirlukast was given to 23 Korean male subjects divided into two genotype groups according to CYP2C9 genotypes, CYP2C9EM (n = 11; CYP2C9*1/*1) and CYP2C9IM (n = 12; 9 and 3 carriers of CYP2C9*1/*3 and *1/*13...
Source: Archives of Pharmacal Research - July 3, 2016 Category: Drugs & Pharmacology Authors: Lee HJ, Kim YH, Kim SH, Lee CM, Yang AY, Jang CG, Lee SY, Bae JW, Choi CI Tags: Arch Pharm Res Source Type: research
Supersaturation of zafirlukast in fasted and fed state intestinal media with and without precipitation inhibitors.
Abstract
Poor water solubility is a bottle neck in the development of many new drug candidates, and understanding and circumventing this is essential for a more effective drug development. Zafirlukast (ZA) is a leukotriene antagonist marketed for the treatment of asthma (Accolate®).ZA is poorly water soluble, and is formulated in an amorphous form (aZA) to improve its solubility and oral bioavailability. It has been shown that upon dissolution of aZa, the concentration of ZA in solution is supersaturated with respect to its stable crystalline form (ZA monohydrate), and thus, in theory, the bioavailability...
Source: European Journal of Pharmaceutical Sciences - May 30, 2016 Category: Drugs & Pharmacology Authors: Madsen CM, Boyd B, Rades T, Müllertz A Tags: Eur J Pharm Sci Source Type: research
Modulation of LOX and COX pathways via inhibition of amyloidogenesis contributes to mitoprotection against β-amyloid oligomer-induced toxicity in an animal model of Alzheimer's disease in rats
Publication date: July–August 2016 Source:Pharmacology Biochemistry and Behavior, Volumes 146–147 Author(s): Jaspreet Kalra, Puneet Kumar, Abu Bakar Abdul Majeed, Atish Prakash Several lines of evidence indicate that beta amyloid (β-A) production, neurofibrillary tangles and neuroinflammation are interrelated in the pathogenesis of Alzheimer's disease (AD). AD is associated with enhanced β-A production and accumulation resulting in neuroinflammation probably via activation of lipoxygenase (LOX) and cyclooxygenase (COX) pathways. Therefore, the present study was designed to investigate the role of LOX and ...
Source: Pharmacology Biochemistry and Behavior - May 17, 2016 Category: Biochemistry Source Type: research
Capsular Contracture after Breast Augmentation: An Update for Clinical Practice.
Authors: Headon H, Kasem A, Mokbel K
Abstract
Capsular contracture is the most common complication following implant based breast surgery and is one of the most common reasons for reoperation. Therefore, it is important to try and understand why this happens, and what can be done to reduce its incidence. A literature search using the MEDLINE database was conducted including search terms 'capsular contracture breast augmentation', 'capsular contracture pathogenesis', 'capsular contracture incidence', and 'capsular contracture management', which yielded 82 results which met inclusion criteria. Capsular contr...
Source: Archives of Plastic Surgery - October 3, 2015 Category: Cosmetic Surgery Tags: Arch Plast Surg Source Type: research
Antileukotrienes in Upper Airway Inflammatory Diseases
Abstract
Leukotrienes (LTs) are a family of inflammatory mediators including LTA4, LTB4, LTC4, LTD4, and LTE4. By competitive binding to the cysteinyl LT1 (CysLT1) receptor, LT receptor antagonist drugs, such as montelukast, zafirlukast, and pranlukast, block the effects of CysLTs, improving the symptoms of some chronic respiratory diseases, particularly bronchial asthma and allergic rhinitis. We reviewed the efficacy of antileukotrienes in upper airway inflammatory diseases. An update on the use of antileukotrienes in upper airway diseases in children and adults is presented with a detailed literature ...
Source: Current Allergy and Asthma Reports - September 18, 2015 Category: Allergy & Immunology Source Type: research
Two New Polymorphic Cocrystals of Zafirlukast: Preparation,
Crystal Structure, and Stability Relations
Crystal Growth & DesignDOI: 10.1021/acs.cgd.5b00744 (Source: Crystal Growth and Design)
Source: Crystal Growth and Design - July 24, 2015 Category: Chemistry Authors: Antonio Llinas, Rafael Barbas, Mercè Font-Bardia, Michael J. Quayle, Sitaram Velaga and Rafel Prohens Source Type: research
Early growth response gene (EGR)-1 regulates leukotriene D4-induced cytokine transcription in Hodgkin lymphoma cells
Publication date: Available online 23 June 2015 Source:Prostaglandins & Other Lipid Mediators Author(s): Hongya Han , Yongtao Xue-Franzén , Xinyan Miao , Edit Nagy , Nailin Li , Dawei Xu , Jan Sjöberg , Magnus Björkholm , Hans-Erik Claesson Classical Hodgkin lymphoma (cHL) has a unique pathological feature characterized by a minority of malignant Hodgkin Reed-Sternberg (H-RS) cells surrounded by numerous inflammatory cells. Cysteinyl-leukotrienes (CysLTs) are produced by eosinophils, macrophages and mast cells in the HL tumor microenvironment. In the present study we have explored the signal transdu...
Source: Prostaglandins and Other Lipid Mediators - June 23, 2015 Category: Lipidology Source Type: research
