Prophylaxis Of Asthma Research Articles

OMEGA-UNSATURATED FATTY ACIDS – THEIR PRESENCE IN THENUTRITIONAL REGIME FOR THE PREVENTION OF CERTAIN SOCIALLY SIGNIFICANT DISEASES

The essential fatty acids provide normal biological functions of the human body and are an important part of the dietary intake in the prophylaxis and prevention of various diseases cardiovascular diseases, hypertension, arthritis, asthma, and autoimmune disorders. In this study, we present the results of a survey on the intake of dietary supplements containing omega-unsaturated fatty acids in addition to the diet to prevent some socially significant diseases. As a result of the survey, to satisfy the respondents' desire regarding the quality of the food supplements offered, we have developed a gas chromatographic method. The results of the study highlight the benefits of taking omega-3 unsaturated fatty acid among different age groups for a better quality of life. We also offer a fast and reliable analytical method to verify the quality and safety of the food supplements on the market in Bulgaria.

An Andrographis paniculata Burm. Nees extract standardized for three main Andrographolides prevents house dust mite-induced airway inflammation, remodeling, and hyperreactivity by regulating Th1/Th2 gene expression in mice

Ethnopharmacological relevanceAndrographis paniculata Burm. Nees (AP) is an herb used traditionally in Indian and Chinese traditional medicine for the treatment of various inflammatory and respiratory tract diseases. However, the anti-inflammatory potential of standardized Andrographis paniculata 50% ethanol extract (APEE50) in the murine model of asthma has not been investigated. Aim of the studyThis study aimed to evaluate the protective anti-inflammatory potential and better understand the underlying mechanism of action of APEE50 in a clinically-relevant mouse asthma model. Thereafter, develop the ethanolic extract of AP as a supplement for asthma prophylaxis. Materials and methodAPEE50 was prepared and standardized for AGP, NAG, and DDAG using a high-performance liquid chromatography system. Asthma was induced according to a 14-day house dust mite (HDM) induction protocol. The prophylactic potential of APEE50 (50 mg/kg – 200 mg/kg) was determined by assessing cardinal asthma features, which included BALF leukocyte and differential cell count, BALF cytokine assay, histology, gene expression, and airway hyperreactivity study. ResultsAPEE50 significantly inhibited HDM-induced airway eosinophilia and neutrophilia. In addition to decreased levels of IL-4, IL-5, IL-13, and eotaxin in bronchoalveolar fluid, APEE50 abrogated HDM-induced airway mucus over-secretion and airway hyper-responsiveness. Administration of APEE50 downregulated HDM-induced upregulation of the oxidative stress enzyme Duox1 (dual oxidase 1) and marginally induced Nfe2l2 (nuclear factor erythroid 2-related factor 2) gene expressions. Similarly, Th2-related (Serpinb2, Clca3a1, Il4 and Il13) and Muc5ac gene expression were significantly downregulated. ConclusionProphylactic administration of APEE50 prevented the progression of HDM-induced asthmatic responses by down-regulating Th2 cytokine gene expression and oxidative stress level.

An overview on phytoconstituents and multiple biological activities of Euphorbia hirta

The major genus in the Euphorbiaceae family, Euphorbia is having more than 1600 species. The Euphorbiaceae family includes the annual weed Euphorbia hirta, sometimes referred to as the asthma plant. It's not just a weed, it also has medical properties. The Chinese Pharmacopoeia and African pharmacopoeia listed E. hirta for many drugs. Along with tropical and temperate regions of the world, Africa, Bangladesh, Australia and India are also home to these therapeutic herbs. The current review discusses its phytoconstituent profile, therapeutic profile and other significant biological characteristics. It includes a number of secondary active compounds, such as polyphenols, flavonoids, steroids, tannins and alkaloids, which act as anti-microbial, anti-fertility, anti-diabetic, anti-inflammatory, anti-cancer, anti-plasmodial, anti-tumor and in the management of many other disorders. Hematuria and gonorrhoea are also treated with E. hirta. In South Africa E. hirta is widely accepted as the prophylaxis of asthma. The herb is utilized as an enema remedy in the Gold Coast. Inflammatory bowel disease, psoriasis and diabetic-induced sores are just a few of the chronic inflammatory disorders that can be treated topically using the alcohol-based fruit and leaf extract of E. hirta. For the purpose of identifying and creating a monograph on E. hirta, this review may be used.

Mannitol Challenge to Assess Therapy Response in Asthmatic Children: An Interventional Cohort Study.

Bronchial provocation tests, such as the mannitol challenge, can be performed to identify and quantify the severity of bronchial hyperresponsiveness in asthmatic patients. Studies of the mannitol challenge as a monitoring tool in asthmatic children are limited. Our primary aim was to compare the bronchial hyperresponsiveness to mannitol in treatment-naive asthmatic children between baseline and three months after receiving the indicated asthma prophylaxis. Twenty-three asthmatic patients aged 4-16 years were analyzed in this prospective cohort study. All subjects underwent the mannitol challenge at baseline and after three months of treatment with budesonide ± formoterol. The difference in the provocative dose of mannitol to induce a 15% drop in FEV1 (PD15) between baseline and follow-up, as well as its association with the presence of exercise-induced or nocturnal asthma symptoms, were evaluated. The PD15 value increased significantly post-treatment (228.5 mg [4.50-458.15]; p = 0.04). Independently of the evaluation time point, the PD15 values were significantly lower in the presence of nocturnal asthma symptoms (490 mg [122-635] vs. 635 mg [635-635]; p = 0.03), whereas there was no association between the PD15 value and the presence of exercise-induced asthma (p = 0.73). These results suggest that bronchial hyperresponsiveness to mannitol may be a potential monitoring tool in the pediatric asthmatic population, reflecting therapy response in children receiving prophylactic treatment.

Measuring the awareness of the family with asthmatic child about the care and prophylaxis of asthma in Unaizah city, Saudi Arabia

Measuring the awareness of the family with asthmatic child about the care and prophylaxis of asthma in Unaizah city, Saudi Arabia

MONTELUKAST AND LEVOCETERIZINE FIXED DOSE COMBINATION-AN EVIDENCE REVIEW

Indian pharma market is flooded with various fixed drug combinations. Among them, one of the widely used FDC is montelukast + levocetirizine. This is prescribed for the patients of any age group (paediatrics, adults and geriatric) and used as a long term therapy for the treatment of conditions such as prophylaxis, acute and chronic types of asthma, relief of symptoms of seasonal and perennial allergic rhinitis, prevention of exercise induced bronchoconstriction and chronic idiopathic urticaria. It is very essential to check the rational use of this FDC. Generally fixed dose combinations create confusions among physicians, because it contains more than one drug in various doses and it is very difficult to remember all these details and another issue with the FDCs are that the entire FDC cannot be used if the patient is contraindicated to any of the drug in the FDC. And patient specific dose calculation is also difficult with FDCs. There are very less clinical trial data available about the safety and efficacy of this agent. Objective of this review article is to check the rational use of montelukast levocetirizine FDC. To achieve the objective, all the literatures related to montelukast levocetirizine FDC were collected and analysed. The study concluded that some differences are there in the pharmacokinetic parameters of both these agents includes duration of action. In dosing also, levocetirizine dose can vary from 2.5mg to 10mg once daily whereas montelukast dosing is 10mg. Rationality of this FDC can be further supported by more clinical trial data to conform the rationality of these FDC.

ЕВОЛЮЦІЯ РЕКОМЕНДАЦІЙ GINA. ПРАКТИЧНІ АСПЕКТИ ЛІКУВАННЯ ПАЦІЄНТІВ З АСТМОЮ ЧЕРЕЗ ПРИЗМУ КЛІНІЧНИХ ДОСЛІДЖЕНЬ

EVOLUTION OF GINA GUIDELINES. PRACTICAL ASPECTS OF ASTHMA MANAGEMENT THROUGH THE PRISM OF CLINICAL TRIALS S. V. Zaikov, F. T. Bogomolov, G. L. Gumeniuk Abstract Through the 28 years lifetime of GINA (Global Initiative for Asthma) recommendations, there’s been a shift in the paradigm of asthma management. GINA is a Global Strategy of treatment and prophylaxis of asthma, established by National Heart, Lung and Blood Institute in collaboration with National Institute of Health and World Health Organization in 1993. First published in 1995 GINA report has become a widespread consensus, which made a basis for clinical recommendations on asthma worldwide. One can define three major periods in evolution of GINA. The first period covered 1994–2004 years since GINA originated and first edition published until experts have recognized the advantage of inhaled rout of asthma drugs administration. It was proved that in many patients the main goal was establishing asthma control, while combination of inhaled corticosteroid with long-acting beta agonist (ICS/LABA) was a preferred option in moderate persistent asthma. In this period it was recommended to chose an approach to managent of asthma, based on scientific evidence, rather then expert’s opinion. In this regard, a second period (2005–2014 years) should be considered outstanding, due to the change in perception of major goals of asthma management, considering exclusively data from numerous studies. Such concepts as patient-medical personnel partnership, patient’s education, guided self-control and goals of treatment have been introduced. GINA recommends to use asthma control as a major approach to treatment instead of severity of disease. Personalized treatment should be aimed on exacerbation risk reduction. Steps 3-5 of treatment algorithm were modified to include ISC-formoterol for maintenance therapy and relief of symptoms (MART-therapy). Third period of GINA started after SYGMA 1 and 2 studies results became available. It was demonstrated that on-demand symptom-relief use of anti-inflammatory therapy with ICS/formoterol combination was highly effective in mild asthma patients. Use of this combination as rescue medication decreased the risk of exacerbation in comparison with short-acting beta agonist (SABA) and may be used in any variant of asthma. Since GINA 2019 edition SABA became not the only one available option even for the mildest forms of asthma. Eventually, in 2021 the culmination of GINA evolution occurred: major algorithm of asthma management has been divided in two tracks: preferred (Track 1) therapy with ICS/formoterol and alternative (track 2) therapy with SABA as rescue medication. The authors of this article review in details the periods of GINA evolution, resulted in dividing asthma management into two tracks, which provide personalized treatment strategy considering all patient’s needs and characteristics such as fast relief of symptoms, decreased risk of exacerbation and establishing asthma control. Key words: asthma, GINA, evolution of treatment approaches. Ukr. Pulmonol. J. 2022;30(1):6–14

Pharmacoeconomic analysis of bronchial asthma prophylaxis in adults and children with allergic rhinitis by means of sublingual allergen-specific immunotherapy

BACKGROUND: Allergic rhinitis is the most common chronic allergic disease worldwide, and bronchial asthma (BA) is one of the most severe complications of allergic rhinitis. Clinical studies reported that sublingual allergen-specific immunotherapy can reduce the incidence of bronchial asthma in children and adults. However, allergen-specific immunotherapy is rather expensive and is not reimbursed by the state, which transfers the cost of this therapy to patients.
 AIMS: To evaluate the cost-effectiveness of allergen-specific immunotherapy in children and adults with allergic rhinitis and/or allergic rhinoconjunctivitis
 MATERIALS AND METHODS: The study hypothesized based on study results by Devillier P. et al. in 2019, to which the incidence of asthma was 13.7% and 17.0% in the sublingual allergen-specific immunotherapy + symptomatic therapy and the symptomatic therapy group, respectively (odds ratio: 0.776, 95% confidence interval [0.622; 0.968]). Pharmacoeconomic study based on decision tree model. Costs taken into account are the following: allergen-specific immunotherapy, symptomatic therapy, diagnostics, and routine follow-up visits due to bronchial asthma, outpatient bronchial asthma drug therapy, and hospitalization due to bronchial asthma. The modeling horizon was 5 years, including 2 years of allergen-specific immunotherapy therapy and 3 years of follow-up.
 RESULTS: The cost per patient when using allergen-specific immunotherapy in combination with symptomatic therapy was 166,711.93 rubles, whereas with symptomatic therapy was 101,700.35 rubles. The cost-effectiveness ratio for allergen-specific immunotherapy in combination with symptomatic therapy was 193,177.20 rubles per 1 prevented case of asthma, whereas 122,530.55 rubles for symptomatic therapy for 1 prevented case of bronchial asthma. Thus, the cost of 1 averted bronchial asthma case when using allergen-specific immunotherapy in combination with symptomatic therapy is 57.7% higher than with symptomatic therapy. The cost-benefit analysis result revealed that the incremental cost-utility ratio for an additional year of life adjusted for its quality when performing sublingual allergen-specific immunotherapy in combination with symptomatic therapy compared with symptomatic therapy alone in children and adults was 567,365.48 rubles, which is less than the calculated willingness to pay threshold (RUB 2,248,898.50).
 CONCLUSIONS: The comparison results of the cost of 1 added quality adjusted life years and willingness to pay threshold concluded that sublingual allergen-specific immunotherapy in combination with symptomatic therapy compared to symptomatic therapy alone is potentially cost-effective in children and adults with allergic rhinitis.

Zafirlukast ameliorates Docetaxel-induced activation of NOD-like receptor protein 3 (NLRP3) inflammasome, mediated by sirtuin1 (SIRT1) in hepatocytes

ABSTRACT Docetaxel-associated liver injury has become a serious public health problem, resulting in therapy discontinuation, liver failure, and death. Zafirlukast is a typical leukotriene receptor antagonist used for prophylaxis and chronic treatment of asthma. In this study, we investigate whether treatment with Zafirlukast could alleviate Docetaxel-induced cytotoxicity in hepatocytes. Our results indicate that Zafirlukast mitigated Docetaxel-induced toxicity in LO-2 hepatocytes. Firstly, Zafirlukast reduced the production of 8-hydroxy-2p-deoxyguanosine (8-OHdG) and increased the levels of reduced glutathione (GSH) against Docetaxel. Secondly, Zafirlukast elevated the levels of mitochondrial membrane potential (ΔΨm) and adenosine triphosphate (ATP). Thirdly, Zafirlukast prevented Docetaxel-induced release of lactate dehydrogenase (LDH) and increased cell viability of LO-2 hepatocytes against Docetaxel. We also found that Zafirlukast ameliorated Docetaxel-induced apoptosis by reducing Caspase-3 and Caspase-9 activity. Mechanistically, our results demonstrate that Zafirlukast inhibited the activation of NOD-like receptor protein 3 (NLRP3), mediated by SIRT1. Based on these findings, we conclude that the administration of Zafirlukast might have a protective effect against Docetaxel-induced cytotoxicity in hepatocytes.

Development and validation of a set of patient reported outcome measures to assess effectiveness of asthma prophylaxis

BackgroundIn the local setting, asthma control is assessed by symptoms and signs elicited by clinicians because of the limited availability of spirometry. Hence, we intended to develop a patient reported outcome measure (PROM) with more holistic interpretation that could also serve as a tool to measure the asthma control in resource limited settings. Therefore, this study was carried out in Northern Sri Lanka to develop and validate the Asthma Control PROM (AC-PROM) Tamil to measure the effectiveness of asthma prophylaxis based on symptoms, exacerbation and limitation of activity which could also serve as an easy measure of asthma control to the provider.MethodsThe AC-PROM Tamil was developed in 3 steps: item generation, item reduction and psychometric evaluation. Items were generated through thematic analysis from focus group discussions among patients with asthma. Items were converted to an interviewer administered questionnaire in Tamil in the format of 5-point Likert scale. Item reduction was done by two rounds of online Delphi surveys among 10 experts and an exploratory factor analysis among 200 patients with asthma. The face and content validity were assessed by a panel of experts during Delphi survey and patients during the pre-test of the tool. Criterion validity of the tool was assessed against the forced expiratory volume in one second of 187 patients with asthma. The cut-off value to assess the asthma control was determined by receiver operating characteristic curve. Reliability was verified by Cronbach’s alpha coefficient.ResultsFrom thematic analysis of focus group discussions 10 items were generated. One item was removed during Delphi survey. Exploratory factor analysis indicated removal of another item with 8 items categorised into two factors. Cronbach’s alpha coefficient of factors 1 and 2 were 0.821 and 0.903 respectively, indicating good reliability. Observations made by experts and responses made by patients were incorporated to improve the clarity and relevance of the items. Criterion validity was demonstrated by significant correlation between the AC-PROM Tamil and forced expiratory volume in one second (r = 0.66, p = 0.001). The cut-off value of the AC-PROM Tamil to detect asthma control was 28.5 with 79% (95% CI 71.3–86.9) sensitivity and 71% (95% CI 61.9–79.6) specificity. The AC-PROM Tamil showed moderate accuracy (the area under the receiver operating characteristic curve = 0.796; 95% CI 0.73–0.86). Response rate of the AC-PROM Tamil was 100% and time taken to complete was 3–4 min.ConclusionThe AC-PROM Tamil is a simple, feasible and reasonably accurate tool to assesses the effectiveness of asthma prophylaxis, particularly in resource limited settings.

Fabrication, characterization and optimization of nanostructured lipid carrier formulations using Beclomethasone dipropionate for pulmonary drug delivery via medical nebulizers

Aerosolization is a non-invasive approach in drug delivery for localized and systemic effect. Nanostructured lipid carriers (NLCs) are new generation versatile carriers, which offer protection from degradation and enhance bioavailability of poorly water soluble drugs. The aim of this study was to develop and optimize NLC formulations in combination with optimized airflow rates (i.e. 60 and 15 L/min) and choice of medical nebulizers including Air jet, Vibrating mesh and Ultrasonic nebulizer for superior aerosolization performance, assessed via a next generation impactor (NGI). Novel composition and combination of NLC formulations (F1 – F15) were prepared via ultrasonication method, employing five solid lipids (glycerol trimyristate (GTM), glycerol trilaurate (GTL), cetyl palmitate (CP), glycerol monostearate (GMS) and stearic acid (SA)); and three liquid lipids (glyceryl tributyrate (GTB), propylene glycol dicaprylate/dicaprate (PGD) and isopropyl palmitate (IPP)) in 1:3 w/w ratios (i.e. combination of one solid and one liquid lipid), with Beclomethasone dipropionate (BDP) incorporated as the model drug. Out of fifteen BDP-NLC formulations, the physicochemical properties of formulations F7, F8 and F10 exhibited desirable stability (one week at 25 °C), with associated particle size of ~241 nm, and >91% of drug entrapment. Post aerosolization, F10 was observed to deposit notably smaller sized particles (from 198 to 136 nm, 283 to 135 nm and 239 to 157 nm for Air jet, Vibrating mesh and Ultrasonic nebulizers, respectively) in all stages (i.e. from stage 1 to 8) of the NGI, when compared to F7 and F8 formulations. Six week stability studies conducted at 4, 25 and 45 °C, demonstrated F10 formulation stability in terms of particle size, irrespective of temperature conditions. Nebulizer performance study using the NGI for F10 identified the Air jet to be the most efficient nebulizer, depositing lower concentrations of BDP in the earlier stages (1–3) and higher (circa 82 and 85%) in the lateral stages (4–8) using 60 and 15 L/min airflow rates, when compared to the Vibrating mesh and Ultrasonic nebulizers. Moreover, at both airflow rates, the Air jet nebulizer elicited a longer nebulization time of ~42 min, facilitating aerosol inhalation for prophylaxis of asthma with normal tidal breathing. Based on characterization and nebulizer performance employing both 60 and 15 L/min airflow rates, the Air jet nebulizer offered enhanced performance, exhibiting a higher fine particle dose (FPD) (90 and 69 µg), fine particle fraction (FPF) (70 and 54%), respirable fraction (RF) (92 and 69%), and lower mass median aerodynamic diameter (MMAD) (1.15 and 1.62 µm); in addition to demonstrating higher drug deposition in the lateral parts of the NGI, when compared to its counterpart nebulizers. The F10 formulation used with the Air jet nebulizer was identified as being the most suitable combination for delivery of BDP-NLC formulations.

Characterization of Negative Allosteric Modulators of the Calcium-Sensing Receptor for Repurposing as a Treatment of Asthma.

Asthma is still an incurable disease, and there is a recognized need for novel small-molecule therapies for people with asthma, especially those poorly controlled by current treatments. We previously demonstrated that calcium-sensing receptor (CaSR) negative allosteric modulators (NAMs), calcilytics, uniquely suppress both airway hyperresponsiveness (AHR) and inflammation in human cells and murine asthma surrogates. Here we assess the feasibility of repurposing four CaSR NAMs, which were originally developed for oral therapy for osteoporosis and previously tested in the clinic as a novel, single, and comprehensive topical antiasthma therapy. We address the hypotheses, using murine asthma surrogates, that topically delivered CaSR NAMs 1) abolish AHR; 2) are unlikely to cause unwanted systemic effects; 3) are suitable for topical application; and 4) inhibit airway inflammation to the same degree as the current standard of care, inhaled corticosteroids, and, furthermore, inhibit airway remodeling. All four CaSR NAMs inhibited poly-L-arginine-induced AHR in naïve mice and suppressed both AHR and airway inflammation in a murine surrogate of acute asthma, confirming class specificity. Repeated exposure to inhaled CaSR NAMs did not alter blood pressure, heart rate, or serum calcium concentrations. Optimal candidates for repurposing were identified based on anti-AHR/inflammatory activities, pharmacokinetics/pharmacodynamics, formulation, and micronization studies. Whereas both inhaled CaSR NAMs and inhaled corticosteroids reduced airways inflammation, only the former prevented goblet cell hyperplasia in a chronic asthma model. We conclude that inhaled CaSR NAMs are likely a single, safe, and effective topical therapy for human asthma, abolishing AHR, suppressing airways inflammation, and abrogating some features of airway remodeling. SIGNIFICANCE STATEMENT: Calcium-sensing receptor (CaSR) negative allosteric modulators (NAMs) reduce airway smooth muscle hyperresponsiveness, reverse airway inflammation as efficiently as topical corticosteroids, and suppress airway remodeling in asthma surrogates. CaSR NAMs, which were initially developed for oral therapy of osteoporosis proved inefficacious for this indication despite being safe and well tolerated. Here we show that structurally unrelated CaSR NAMs are suitable for inhaled delivery and represent a one-stop, steroid-free approach to asthma control and prophylaxis.

A simple and sensitive HPLC-MS/MS assay for the quantitation of montelukast in cell-based systems in vitro pulmonary drug permeability study

Montelukast is a potent and selective antagonist of the cysteinyl leukotriene receptor 1 subtype (CysLT1) and widely used in the form of oral tablets and granules for asthma prophylaxis and treatment. Recently, due to the pulmonary inhaled administration can limit montelukast distribution in the systemic circulation, avoid the first-pass metabolism and have better therapeutic effects in respiratory disease treatment, explore alternative routes of administration, like delivery of montelukast via an inhaled, is a new research trend for montelukast. The aim of the current study was to develop and validate a simple, accurate, highly sensitive and selective liquid chromatography-tandem mass spectrometry method (LC–MS/MS) for determination of montelukast in an in vitro cell-based pulmonary pharmacokinetics system model, which can be used to be a better understanding the fate of inhaled montelukast in the lungs. In this study, montelukast was extracted by protein precipitation with acetonitrile containing labeled montelukast. The chromatography was performed on an Agilent Eclipse plus C8 column (4.6 mm × 100 mm, 3.5 μm, Darmstadt, Germany) operating at 35 ◦C. The mobile phase consisted of acetonitrile: 20 mM ammonium formate buffer (80: 20, v/v), was delivered at a flow rate of 0.5 mL/min. montelukast and the internal standard were both eluted at 4.2 min. A linear (1/x2) relationship was used to perform the calibration over an analytical range from 0.5 to 600 ng/mL. The intra- and inter-batch precision expressed as CV for four QC samples including LLOQ range from 1.14 % to 6.25 %. The intra- and inter-batch accuracy for four concentrations of montelukast were in the range of 95.19%–104.1%. All the values for accuracy and precision were within the acceptance range. The method met all the bioanalytical method validation requirements by ICH and was suitable for the assay of montelukast which in the in vitro cell-based pulmonary pharmacokinetics system model.

Hydrophobic ion pair loaded self-emulsifying drug delivery system (SEDDS): A novel oral drug delivery approach of cromolyn sodium for management of bronchial asthma.

The aim of the present study is to develop a self-emulsifying drug delivery system (SEDDS) for the hydrophobic ion pair (HIP) complex of cromolyn sodium (CS), in order to enhance its intestinal absorption and biological activity. Two ion pairing agents (IPAs) were investigated: hexadecyl pyridininum chloride (HPC) and myristyl trimethyl ammonium bromide (MTAB). The optimum binding efficiency for complexation between investigated IPAs and CS was observed at a molar ratio of 1.5:1, where CS binding efficiency was found to be 76.10±2.12 and 91.37±1.73% for MTAB and HPC, respectively. The two prepared complexes exhibited a significant increase in partition coefficient indicating increased lipophilicity. The optimized CS-HIP complex was incorporated into SEDDS formulations. SEDDS formulations F2 (40% oleic acid, 40% BrijTM98, 20% propylene glycol) and F3 (25% oleic acid, 50% BrijTM98, 25% propylene glycol) exhibited nanometric droplet diameters with monodisperse distribution and nearly neutral zeta potential values. Ex vivo intestinal permeation study, using the non-everted gut sac technique, revealed a significantly higher cumulative amount of permeated drug, after 2h, for F2 and F3 (53.836 and 77.617µg/cm2, respectively) compared to 8.649µg/cm2 for plain CS solution. The in vivo evaluation of plain CS solution compared to F2 and F3 was conducted in an ovalbumin sensitization-induced bronchial asthma rat model. Lung function parameters (tidal volume and peak expiratory flow), biochemical parameters (interleukin-5, immunoglobulin-E, myeloperoxidase and airway remodelling parameters) were assessed in addition to histopathological examination. The results indicated the superiority of F3 followed by F2 compared to plain CS solution for prophylaxis of bronchial asthma in rats.

DESIGN AND DEVELOPMENT OF MONTELUKAST SODIUM FAST DISSOLVING FILMS FOR BETTER THERAPEUTIC EFFICACY

The oral route is most popular route for the administration of therapeutic agents because of the low cost of therapy and ease of administration lead to high levels of patient compliance. The most popular oral solid dosage forms are tablets and capsules. Many patients find it difficult to swallow tablets and hard gelatin capsules particularly pediatric and geriatric patients and do not take their medicines as prescribed. The objective of this research was to prepare fast dissolving oral thin film (FDOTF) containing Montelukast sodium is indicated for the prophylaxis and chronic treatment of asthma to enhance convenience and compliance to the elderly and pediatric patients for better therapeutic efficacy. The present investigation was undertaken with the objective of formulating of the montelukast sodium fast dissolving oral thin films allowing fast reproducible drug dissolution in oral cavity thus bypassing first pass metabolism. The film were prepared by using polymers such as hydroxypropyl methyl cellulose (HPMC) and Maltodextrin, plasticizer such as PEG 400, by a solvent casting method. They were evaluated for physical characteristics such as thickness, uniformity of weight, folding endurance, drug content, surface ph, percentage elongation and tensile strength, drug polymers compatibility by FTIR study, scanning electron microscopy and in vitro drug release. The formulations were subjected to disintegration, in-vitro drug release test. The in vitro disintegration time of the optimized batch F4 was found to be 20 sec. The optimized batch was found to be stable for 1 month under specified stability conditions.

Neuroprotection by Montelukast against Rotenone-Induced Rat Brain Damage

Montelukast is a cysteinyl-leukotriene receptor antagonist used in asthma prophylaxis. In this study, the effect of montelukast (10 or 20 mg/kg) on neuronal damage and oxidative stress induced in the rat brain by rotenone was examined. Rats were treated with rotenone subcutaneously at 1.5 mg/kg every other day alone or along with montelukast. The control group received the vehicle dimethyl sulfoxide (DMSO). The results showed that compared with the vehicle-treated group, rotenone resulted in increased brain lipid peroxidation by 84.5% as assessed by malondialdehyde (MDA) content. Nitric oxide increased by 77.4% while reduced glutathione (GSH) and total antioxidant capacity (TAC) decreased by 37.7% and 68.6%, respectively. In addition, the activities of superoxide dismutase (SOD), paraoxonase-1 (PON-1), and butyrylcholinesterase (BChE) significantly decreased by 34.6%, 68%, and 75.2%, respectively, after rotenone injection. Rotenone caused neurodegenerative changes in the cerebral cortex and substantia nigra. The administration of montelukast along with rotenone decreased MDA by 34.1–53.6%, nitric oxide by 51.6–64.7%, increased GSH content by 20.7–65.8%, and increased TAC by 109.6–156.2%. SOD activity increased by 50–62.5%, PON-1 activity by 161.1–203.7%, and BChE activity by 135.3–274.3% compared with respective rotenone control values. The rotenone-induced neuronal damage was ameliorated dose-dependently by montelukast. These results indicate that montelukast exerts a neuroprotective effect in the rotenone model of neurotoxicity. The neuroprotective action of montelukast is likely to involve an inhibitory effect on oxidative stress and nitric oxide. It is suggested that montelukast could be of value in the adjunctive treatment of Parkinson’s disease.

Прогнозування розвитку та оптимізація профілактики бронхіальної астми у дітей із сезонною алергією

Резюме . У статті представлені результати дослідження особливостей перебігу сезонної алергії у 108 дітей.<br />Сформовано дві групи пацієнтів. Основну групу склали 48 дітей, у яких сезонна алергія проявлялася поєднанням<br />сезонного ринокон’юнктивіту або риніту та бронхіальної астми, а в групу порівняння увійшли 60 дітей, у яких<br />сезонна алергія проявлялася сезонним алергічним ринокон’юнктивітом і/або сезонним алергічним ринітом.<br />Встановлені особливості клінічного перебігу сезонної алергії в групах порівняння і виділені фактори, пов’язані<br />з формуванням астми у дітей з сезонним алергічним ринокон’юнктивітом або сезонним алергічним ринітом.<br />Визначення найвагоміших факторів, пов’язаних з прогресуванням сезонної алергії, дозволило запропонувати<br />шляхи оптимізації профілактики розвитку бронхіальної астми у таких дітей.<br />Ключові слова : діти, сезонна алергія, астма, профілактика.

G308(P) Parents think that ‘medicines for children’ reaches nice places:

Background Whilst only 20% of content discussed in a consultation is retained, it’s improved by giving additional written information. Patients are able to use written leaflets to consolidate their knowledge away from the stressful environment of a patient-doctor discussion. Such written information may increase treatment compliance and concordance. The ‘Medicines for Children’ website is designed to provide practical and reliable advice for families about giving medicine to their children. It has a variety of leaflets, videos and web-based information on over 200 children’s medications. It’s a partnership between the Royal College of Paediatrics and Child Health, the Neonatal and Paediatric Pharmacists Group and WellChild; a charity for parents and carers. Objective To evaluate the ‘Medicines for Children’ website and information sheets, against the NICE quality standard 15; Understanding Treatment Options and NICE Medicines adherence guideline 76; involving patients in decision about prescribed medicines. Methods A questionnaire was designed against the specific criteria set out in NICE quality standard 15 and clinical guideline 76. Questions focused on the layout, language and content of the leaflet, particularly information regarding the treatment risks and benefits. Data was collected from a convenience sample of parents attending children’s outpatient clinics. Qualitative feedback was also sought. Parents were asked to read the leaflet on ‘Beclametasone inhaler for asthma prophylaxis’ and answer the questionnaire as though their child were starting on this medication. Results 106 parents participated. 16 declined. Parents comments included: ‘clearly laid-out with simple sub-headings’, ‘written in a way that everyone can understand’. They suggested future developments should include: ‘pictures for adults with lower literacy levels’ and ‘having the leaflets in both English and Welsh.’ Conclusion Medicines for Children information leaflets fulfil NICE standards and provide high quality information about children’s medications which is highly valued by families.

Effect of delivery device on systemic exposure to inhaled fluticasone propionate in children with asthma

Effect of delivery device on systemic exposure to inhaled fluticasone propionate in children with asthma

Bioequivalence of two formulations of montelukast sodium 4 mg oral granules in healthy adults.

Montelukast is an effective and well-tolerated treatment for the prophylaxis and chronic treatment of asthma, acute prevention of exercise-induced bronchoconstriction and symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis. The aim of the study was to compare bioavailability, and characterise the pharmacokinetic profile and safety of Sandoz generic montelukast 4 mg oral granules relative to Singulair® mini (Merck, Sharp & Dohme). An open-label, randomised, single-dose, two-treatment, two-period, two-sequence, two-way crossover bioequivalence study was conducted in healthy male volunteers aged 18–55 years, under fasting conditions. The duration of the clinical part of the trial was ≈ 11 days. Montelukast levels in plasma were quantified using a validated liquid chromatography tandem mass spectrometry method, and pharmacokinetic parameters calculated from the drug concentration–time profile using a non-compartmental model. A total of 40 subjects completed both study periods. The ratio test/reference of geometric least squares means was calculated for both formulations of montelukast for the In-transformed pharmacokinetic parameters; the 90% confidence intervals (CIs) were within the pre-defined limits of 80.00–125.00%: 92.2% (90% CI: 87.42–97.30%) for Cmax, 98.1% (90% CI: 94.49–101.81%) for AUC0–t and 97.6% (90% CI: 94.14–101.27%) for AUC0–∞. Two study subjects each reported one mild adverse event: dyspepsia (possibly related to study medication) and throat pain (not considered related to study medication). Sandoz montelukast 4 mg oral granules are bioequivalent to Singulair® 4 mg mini oral granules, with a similar safety profile. This suggests that these two preparations can be considered interchangeable in clinical practice.