Montelukast Research Articles

Advanced Derivative Spectroscopic Method for Estimation of Montelukast and Bilastine in Their Tablet Dosage Form

The present work aims to develop and validate the advanced derivative spectroscopic method for estimation of Montelukast (MON) and Bilastine (BIL) in their tablet dosage form. This tablet dosage form is used for anti-asthmatic and allergic rhinitis. The developed method can be applied for simultaneous estimation of Montelukast and Bilastine in their combined dosage form. For this advanced derivative method, the absorbance at 226.8 nm (ZCP of Montelukast) and 326.4nm (ZCP of Bilastine) was used to estimate Montelukast and Bilastine, respectively. The developed method is validated by ICH Q2R1 guidelines with validation parameters like linearity, LOD, LOQ, accuracy, precision, robustness, ruggedness and assay were performed using this guideline. The method was found to be linear in the concentration range of 2-14 µg/mL for Montelukast (R2 = 0.999) and 4–28 µg/mL for Bilastine (R2 =0.9997). LOD and LOQ found 0.1216 and 0.3686 for MON, and 0.3406 and 1.0320 for BIL. The precision study wasa carried out by comparing on 3 different concentrations and the result of their %RSD was is less than 2%. Robustness study carried out by the change in scanning speed and change in methanol manufacturer and Ruggedness study carried out by different analyst. Assay study was performed using tablet formulation. The developed method was utilized for simultaneous estimation of Montelukast and Bilastine for its tablet dosage form.

Effects of montelukast sodium tablets combined with pulmicort aerosol in the treatment of children with asthma and its influence on EOS, IL-4, IgE, TNF-α

Objective To investigate the effect of montelukast sodium tablets combined with pulmicort aerosol in the treatment of children with asthma, and its influence on eosinophil (EOS), interleukin-4 (IL-4), immunoglobulin E (IgE), tumor necrosis factor-α (TNF-α). Methods From March 2018 to March 2019, 142 children with asthma admitted to Hangzhou Dajiangdong Hospita were randomly divided into observation group (71 cases) and control group (71 cases) according to the digital table.The patients in the observation group were treated with montelukast sodium tablets combined with pulmicort aerosol, while patients in the control group were treated with pulmicort aerosol.Both two groups were treated for 2 weeks.The levels of EOS, IL-4, IgE and TNF-α, day and night asthma symptom scores and blood gas analysis indicators before and after treatment were compared between the two groups. Results The total effective rate of the observation group (91.55%) was higher than that of the control group (74.65%) (χ2=7.220, P<0.05). After treatment, the scores of asthma symptoms in day[(0.38±0.12)points] and night[(0.42±0.14)points] in the observation group were lower than those in the control group[(0.87±0.19)points and (0.93±0.25)ponts](t=18.373, 14.998, all P<0.05). After treatment, the levels of EOS[(0.38±0.09)×109/L], IL-4[(13.89±3.25)ng/L], IgE[(109.35±16.57)kU/L] and TNF-α[(1.25±0.12)ng/L] in the observation group were lower than those in the control group[(0.73±0.13)×109/L, (18.36±2.70)ng/L, (164.53±23.51)kU/L and (1.49±0.15)ng/L](t=18.652, 8.914, 16.165, 10.528, all P<0.05). Conclusion Montelukast sodium tablets combined with pulmicort aerosol is effective in the treatment of children with asthma.It can reduce the levels of EOS, IL-4, IgE and TNF-α, alleviate the symptoms of daytime and night asthma. Key words: Asthma; Eosinophils; Interleukin-4; Immunoglobulin E; Tumor necrosis factor-a; Montelukast sodium; Pulmicort aerosol; child

Separation and Simultaneous Quantitation of Montelukast Sodium and Ebastine in Tablets by using Stability-Indicating Liquid Chromatographic Method

Objectives: A precise, accurate and selective stability-indicating reverse&nbsp;phase high performance liquid chromatographic assay method has been&nbsp;developed for the simultaneous quantitative determination of Montelukast&nbsp;sodium and Ebastine in tablets. Methods: The chromatographic separation&nbsp;of drugs was attained by using Hypersil octadecyl silane C18 (250 x 4.6&nbsp;mm, 5μm) column at room temperature. The composition of mobile phase&nbsp;was methanol, acetonitrile and 0.02M ammonium acetate buffer (pH 5.5&nbsp;adjusted with dilute acetic acid) in the ratio of 80:15:05 v/v/v and flow rate&nbsp;of mobile phase 1.0 ml/min with isocratic elution. The signal of eluents&nbsp;was observed at 244 nm by using diode array detector. Results: The retention&nbsp;time of Montelukast sodium and Ebastine were found to be 4.28 min&nbsp;and 6.63 min, respectively. The linearity ranges for both drugs were found&nbsp;to be 10-50 μg/ml and the percent recoveries were found to be 99.16%&nbsp;and 100.12% for Montelukast sodium and Ebastine respectively. The drug&nbsp;substances and drug products were treated with various forced degradation&nbsp;conditions like acid hydrolysis, alkali hydrolysis, oxidative degradation,&nbsp;thermal degradation and photolytic degradation. The degradants were efficiently&nbsp;separated from the drugs by using optimized chromatographic conditions.&nbsp;The developed method was validated as per recommendation parameters&nbsp;of International conference on harmonization guidelines Q2(R1).&nbsp;Conclusion: The validation parameters indicate that the drug substances&nbsp;were efficiently separated from its degradants and developed method can&nbsp;be routinely applied for the simultaneous quantitative determination of&nbsp;Montelukast sodium and Ebastine in combined tablet formulation in the&nbsp;quality control laboratory.

Title DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHODS FOR DETERMINATION OF LEUKOTRIENE RECEPTOR ANTAGONIST MONTELUKAST SODIUM IN BULK AND PHARMACEUTICAL FORMULATIONS

Objective: Simple, sensitive, precise, reproducible, and validated visible spectrophotometric methods have been developed for the determination of leukotriene receptor antagonist drug, namely, montelukast (MNT) sodium in bulk and pharmaceutical preparations.&#x0D; Methods: Three spectrophotometric methods are based on the formation of yellow-colored ion-pair complexes between MNT sodium and three dyes, bromocresol green, bromophenol blue, and methyl orange with absorption maxima at 420, 416, and 426 nm, respectively.&#x0D; Results: The stoichiometric ratio of the formed ion-pair complexes was found to be 1:1 (drug:reagent) for all methods, as deduced by Job’s method of continuous variation. Several parameters such as pH, buffer type and volume, reagent volume, sequence of addition, and effect of extracting solvent were optimized to achieve high sensitivity, stability, low blank reading, and reproducible results. Under the optimum conditions, linear relationships with good correlation coefficients (0.9993–0.9999) were found over the concentration ranges of 1.0–10, 1.0–12, and 1.0–16 μg/mL with a limit of detection of 0.30, 0.29, and 0.27 μg/mL for bromocresol green, bromophenol blue, and methyl orange methods, respectively.&#x0D; Conclusion: The proposed methods were validated in accordance with ICH guidelines and successfully applied to the analysis of MNT sodium in pharmaceutical formulations. Statistical comparison of the results obtained by applying the proposed methods with those of the reference method revealed good agreement and proved that there was no significant difference in the accuracy and precision between the results.

Radioprotective effects of montelukast, a selective leukotriene CysLT1 receptor antagonist, against nephrotoxicity induced by gamma radiation in mice.

In this study, we evaluated the renal protective effects of montelukast (MLK) against ionizing radiation (IR) induced nephrotoxicity in mice. Radioprotective effects of MLK were assessed by biochemical analysis including measurements of kidney malondialdehyde (MDA), reduced glutathione (GSH), and serum creatinine and urea levels. Besides, for further evaluation of protective effects of MLK on renal system, 99m Tc-dimercaptosuccinic acid (DMSA) has been applied. The total antioxidant capacity of MLK was measured by using 1,1-diphenyl-2-picryl hydrazyl radical reagents and compared with butylated hydroxyl toluene standard antioxidant. The biochemical evaluation revealed that better results have been achieved for the groups administered with MLK than the only radiation group. Besides only IR-treated mice group, those treated with MLK demonstrated a significant decrease in urea and creatinine levels. Statistically, significant differences of MDA and SHG levels (P < .05) were found between the radiation group and MLK plus IR-treated group. Also, 99m Tc-DMSA kidney uptake value (%ID/g) was observed lower for MLK plus IR-treated mice group than only radiation-treated mice group. According to our findings, MLK has a potential role to be used as a renal protective agent against gamma radiation in radiotherapy.

Montelukast ameliorates doxorubicin-induced cardiotoxicity via modulation of p-glycoprotein and inhibition of ROS-mediated TNF-α/NF-κB pathways

Doxorubicin (DOX) cardiotoxicity remains an obstacle to clinical use. The current study examined the possible role of montelukast (ML), which is a cysteinyl leukotrienes receptor antagonist against DOX-induced cardiotoxicity. Male Wistar rats were divided into five groups. The control group, ML group, DOX-challenged group, and DOX/ML-treated groups received ML10 and 20 mg/kg/day for 14 days. Cardiac enzymes; lactate dehydrogenase (LDH); and creatine kinase MB (CK-MB) isoenzymes in serum were measured. Cardiac oxidative/antioxidative parameters were also measured. Cardiac samples were examined for histological images and immunohistochemical expression of tumor necrosis factor alpha (TNF-α)/survivin. Quantitative real-time-polymerase chain reaction was used to detect levels of interleukin (IL)-1β/caspase-3 mRNA. The levels of P-glycoprotein (P-gp), nuclear factor-kappa B , and reactive oxygen species were estimated by enzyme-linked immunosorbent assay. DOX increased serum cardiac enzymes along with oxidative, inflammatory, and apoptotic markers. Both doses of ML significantly ameliorated cardiac enzymes and attenuated all oxidative stress parameters with the enhancement of P-gp activity. It was concluded that ML may be a valuable cardioprotective adjuvant during DOX use.

Formulation and Evaluation of Fast Dissolving Tablet of Montelukast Sodium: Effect of Superdisintegrants

Formulation and Evaluation of Fast Dissolving Tablet of Montelukast Sodium: Effect of Superdisintegrants

Formulation development and in-vitro evaluation of montelukast sodium pressurized metered dose inhaler

Montelukast is used as alternative treatment for asthma. However, some adverse drug reactions have been reported for the oral dosage form of montelukast. To counter this issue, the drug was formulated into a pressurized metered-dose inhaler (pMDI), which delivered montelukast directly to the lower regions of the lungs. Montelukast sodium, mixed with either HFA 134a propellant or a mixed propellant (HFA-134a and HFA227), was formulated into a pMDI with other excipients. The canister was prepared using a pressurized filling method, followed by disk sampling to assess content per spray and content uniformity. The effects of ethanol and polyethylene glycol (PEG) 400 on the fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of the formulation were evaluated. In vitro cytotoxicity of the developed montelukast pMDIs was tested in lung airway cell lines. Their effects on the levels of inflammatory nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), generated from NR8383 alveolar macrophage (AM) cells, were also evaluated. All selected formulations had a FPF >46%, whereas the formulation containing 20% v/v ethanol and 1% v/v PEG 400 showed the highest FPF. The MMADs of all formulations were within 1–5 μm. The montelukast pMDI formulations were found to be non-toxic to lung airway cell lines and did not induce inflammatory NO, TNF-α, or IL-1β production in NR8383 cells.

Effects of montelukast sodium plus budesonide on lung function, inflammatory factors, and immune levels in elderly patients with asthma.

Asthma in elderly patients causes excessive suffering and inconvenience. Regimens with better efficacy and less adverse events are still in need of researches. To investigate the effect of montelukast sodium plus budesonide on lung function, inflammatory factors, and immune levels in elderly asthma patients. A total of 180 patients with asthma were assigned into the control group and the observation group. The control group was given aerosol inhalation of budesonide suspension, while the observation group was given budesonide inhalation and oral montelukast sodium. The treatment effect, lung function (forced expiratory volume in 1s (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF)%), inflammatory factors (interleukin (IL)-4, IL-6, and tumor necrosis factor-α (TNF-α)), and immune level (immunoglobulin (Ig) A, and IgE) were analyzed and compared between the two groups. After treatment, the effective rate was significantly higher in the observation group. The lung function and serum inflammatory factors were improved in both groups. The FEV1, FVC, and PEF% in the observation group were better, and the inflammatory factors IL-4, IL-6, and TNF-α were lower. Patients in both groups showed elevated IgA level and reduced IgE level, and the improvements were more significant in the observation group. There was no significant difference between the two groups in terms of adverse reaction. Montelukast sodium plus budesonide has a promising clinical effect on asthma in elderly patients, effectively improves lung function and immunocompetence, and controls inflammatory response, without increasing the adverse reaction.

LncRNA PCGEM1 strengthens anti-inflammatory and lung protective effects of montelukast sodium in children with cough-variant asthma.

Montelukast sodium is an effective and well-tolerated anti-asthmatic drug. Long non-coding RNAs (lncRNAs) are involved in the treatment of asthma. Therefore, this study aimed to investigate the effect of montelukast sodium on children with cough-variant asthma (CVA) and the role of lncRNA prostate cancer gene expression marker 1 (PCGEM1) in drug efficacy. The efficacy of montelukast sodium was evaluated by assessing the release of inflammatory factors and pulmonary function in CVA children after a 3-month treatment. An ovalbumin (OVA)-sensitized mouse model was developed to simulate asthmatic conditions. PCGEM1 expression in clinical peripheral blood samples and lung tissues of asthmatic mice was determined. Asthmatic mice experienced nasal inhalation of PCGEM1 overexpression with simultaneous montelukast sodium to investigate the roles of PCGEM1 in asthma treatment. The NF-κB axis after PCGEM1 overexpression was detected to explore the underling mechanisms. Consequently, montelukast sodium contributed to reduced levels of pro-inflammatory factors and improved pulmonary function in CVA children. PCGEM1 was poorly expressed in OVA-sensitized asthmatic mice and highly expressed in CVA children with response to the treatment. PCGEM1 overexpression enhanced the anti-inflammatory effects and promoted effects on pulmonary function of montelukast sodium in CVA children and OVA-sensitized asthmatic mice. Furthermore, PCGEM1 inhibited the activation of the NF-κB axis. This study demonstrated the anti-inflammatory and lung-protective effects of montelukast sodium on CVA, which was strengthened by overexpression of PCGEM1. Findings in this study highlighted a potential anti-asthmatic target of montelukast sodium.

The examination of the nephroprotective effect of montelukast sodium and N-acetylcysteine ın renal ıschemia with dimercaptosuccinic acid imaging in a placebo-controlled rat model.

Purpose To determine the nephroprotective effect of NAC and Montelukast Sodium administration against the development of renal damage associated with long warm renal ischemia.Methods Twenty-seven rats were randomly divided into 3 study groups, which received NAC, montelukast and placebo, and 3 rats were included in the sham-treated control group. Medications were given 3 days before the procedure. DMSA renal scintigraphy was performed before and after surgery. The right renal pedicle was occluded for 45 min to induce ischemia and then subjected to reperfusion for 6 h (I/R groups).Results On pathological examination, the mean pathological scores of the montelukast and NAC groups were significantly lower than those of the placebo group. (p <0.05). In biochemical examination, significant differences were found in all parameter levels between the placebo group and the montelukast and NAC groups. (p <0.05) When postoperative DMSA renal scintigraphy measurements and renal function levels were compared, significant differences were found between the montelukast and NAC groups and the placebo and sham groups.Conclusion The administration of NAC and montelukast sodium was seen to have a nephroprotective effect against the development of renal damage associated with warm renal ischemia.

The correlation between total immunoglobulin-E levels and interleukin-13 gene polymorphism in asthmatic children treated with inhaled corticosteroids or montelukast

Background: The aim of this research was to study the possible correlation between single-nucleotide polymorphism of interleukin (IL)-13-1112 C/T with specific parameters in asthmatic children (total serum immunoglobulin-E [TSIgE] levels and asthma severity) treated with montelukast or inhaled corticosteroid. Methods: The study included one hundred asthmatic patients attending Karbala Teaching Hospital for children and similar numbers of healthy unrelated age-matched controls from the same locality of Iraq. TSIgE levels were determined by ELISA technique. DNA was extracted and processed by the allele-specific polymerase chain reaction technique for characterization of genetic variants of IL-13-1112 C/T gene polymorphisms. Results: Iraqi children with asthma showed a lower frequency of the IL-13-1112 CC genotype (13% vs. 16%) for control cases with a higher frequency of the heterozygous IL-13-1112 CT genotype (78% vs. 75%). IL-13-1112 showed significantly negative association with asthma in the dominant, codominant, and overdominant models of inheritance. On the other hand, comparing genotypes of subgroups related to gender, asthma severity, and asthma control showed a nonsignificant difference (P > 0.05). Homozygous wild types of IL-13-1112 TT might be considered protective to Iraqi asthma children. Conclusion: The IL-13 gene may be associated with the level of control in treated asthmatic patients. There is no correlation between TSIgE and the SNP.

Design, Development, Characterization of Solid Lipid Nanoparticles for Oral Administration

A high potential for drug delivery has been attributed to particulate drug carriers, especially small particles such as micro particles and colloidal system in nanometer range. Controlled and targeted delivery is one the most enviable requirements from a carrier, which involves the multidisciplinary site-specific or targeted approach. Nanoparticles have important potential applications for the administration of therapeutic and diagnostic agents. Nanoparticulate drug delivery system may offer plenty of advantages over conventional dosage forms which include improved, reduced toxicity, enhanced biodistribution and improved patient compliance. Pharmaceutical Nanoparticles are subnano sizes structures, which contain drug or bioactive substances within them and are constituted of several tens or hundreds of atoms or molecules and morphologies (amorphous, crystalline, spherical, needles). Montelukast sodium (MKS) is a potent, orally active, and has high affinity and selectively binds to the cysteinyl leukotriene 1 (CysLT1) receptor as compared to the prostanoid, cholinergic or β-adrenergic airway receptor. The main drawback of conventional montelukast formulation is that it undergoes hepatic first pass metabolism. The Cumulative % drug release with respect to time was found to be 95.38% for the optimized batch. From the oral bioavailability study it became evident that enhancement in the bioavailability of MKS was observed after drug-loaded SLNs have been administered in in vivo.

Montelukast Nanocrystals for Transdermal Delivery with Improved Chemical Stability.

A novel nanocrystal system of montelukast (MTK) was designed to improve the transdermal delivery, while ensuring chemical stability of the labile compound. MTK nanocrystal suspension was fabricated using acid-base neutralization and ultra-sonication technique and was characterized as follows: approximately 100 nm in size, globular shape, and amorphous state. The embedding of MTK nanocrystals into xanthan gum-based hydrogel caused little changes in the size, shape, and crystalline state of the nanocrystal. The in vitro drug release profile from the nanocrystal hydrogel was comparable to that of the conventional hydrogel because of the rapid dissolution pattern of the drug nanocrystals. The drug degradation under visible exposure (400–800 nm, 600,000 lux·h) was markedly reduced in case of nanocrystal hydrogel, yielding only 30% and 50% amount of cis-isomer and sulfoxide as the major degradation products, as compared to those of drug alkaline solution. Moreover, there was no marked pharmacokinetic difference between the nanocrystal and the conventional hydrogels, exhibiting equivalent extent and rate of drug absorption after topical administration in rats. Therefore, this novel nanocrystal system can be a potent tool for transdermal delivery of MTK in the treatment of chronic asthma or seasonal allergies, with better patient compliance, especially in children and elderly.

Lecithin-based modified soft agglomerate composite microparticles for inhalable montelukast: Development, tolerability and pharmacodynamic activity

In this work, montelukast (MTK) was incorporated in inhalable soft agglomerates (SA) exhibiting inherent characteristics for deep lung deposition while expressing good flowability and enhanced shelf-life stability. Mannitol and ovalbumin were used as particle shapers and lecithin as binder during microparticles (MPs) preparation by spray drying. The spontaneously agglomerated MPs with an adhesive surface were designed to deagglomerate under the effect of aerosolization with selected dry powder inhaler device, achieving satisfactory lung deposition. A pharmacodynamic study was also undertaken to evaluate MTK-SA effectiveness in asthmatic rats. Optimized SA showed agglomerated small MPs capable of dispersing into individual particles under pressures exceeding 1Bar. They exhibited high respirable fraction of >54% and were able to release MTK in <15 min. MTK-SA, delivered by pulmonary insufflation, was able to equally reduce the inflammatory response in asthmatic rats at a ten fold lower dose compared to oral tablet.

Clinical effect of mometasone furoate nasal spray combined with montelukast in the treatment of children with obstructive sleep apnea hypopnea syndrome

Objective To explore the clinical effect of mometasone furoate nasal spray combined with montelukast in the treatment of children with obstructive sleep apnea hypopnea syndrome (OSAHS), and to analyze its feasibility and clinical application value. Methods From August 2017 to March 2019, 64 children with OSAHS who were treated in the People's Hospital of Jinhua were selected in the study.According to the random number table method, they were divided into the observation group and the control group, with 32 cases in each group.The observation group was treated with mometasone furoate nasal spray combined with montelukast for 12 weeks.The control group was treated with surgical treatment to remove hypertrophic tonsils and/or adenoids.The clinical symptom scores, polysomnography(PSG) monitoring index, adenoid and tonsil size index, and the efficacy after 12 weeks of treatment were compared between the two groups. Results There were no statistically significant differences in symptom scores and minimum arterial oxygen saturation(LSaO2) between the two groups before treatment(all P>0.05). After treatment, the symptom scores and LSaO2 of the control group were (1.90±0.53)points and (94.74±1.54)%, respectively, which of the observation group were (4.00±1.50)points and (85.34±10.57)%, respectively, the differences between the two groups were statistically significant(t=-7.416, 4.972, all P<0.05). There were statistically significant differences in the apnea hypopnea index(AHI) and obstructive apnea index(OAI) between the two groups(all P<0.05). After treatment, the A/N of the adenoids in the observation group was significantly decreased, and the difference in the tonsil classification was statistically significant(Z=-2.602, P<0.05). The effective rate of the observation group was 56.25%(18/32), which was significantly lower than that of the control group [100.00%(32/32)], the difference was statistically significant(χ2=17.920, P<0.05). Conclusion In summary, non-surgical treatment can alleviate OSAHS-related symptoms, reduce the size of tonsils and adenoids, and achieve the purpose of remission or cure.Non-surgical treatment can be selected when patients' families are reluctant to choose surgical treatment. Key words: Sleep apnea, obstructive; Glucocorticoids; Leukotriene antagonists; Tonsillectomy; Adenoidectomy; Polysomnography; Blood gas monitoring, transcutaneous; Ventilation-perfusion ratio; Children

Association of human serum paraoxonase-1 with some respiratory drugs.

In this study, we investigated the effects of certainrespiratory drugs, which are mainly usedon human serum paraoxonase-1 (hPON1; EC 3.1.8.1). hPON1 was purified from human serum, with 354.91 fold and 45% yield by using two simple step procedures including, first, ammonium sulfate precipitation, then, Sepharose-4B-l-tyrosine-1-naphthylamine hydrophobic interaction chromatography. SDS-polyacrylamide gel electrophoresis showed a single protein band belongingto hPON1 with 43 kDa. All the pharmaceutical compounds inhibited the PON1 enzyme highly at the micromolar level. The obtained IC50 values for nine different pharmaceutics ranged from 0.219 μM (salbutamol sulfate) to 67.205 μM (montelukast sodium). So, all drugs couldbe considered as potent hPON1 inhibitors. Ki values and inhibition types were determined by Lineweaver-Burk graphs. While varenicline tartrate and moxifloxacin hydrochloride inhibited the enzyme in a noncompetitive manner, others inhibited it in a mixed manner.

Montelukast Improves Symptoms and Lung Function in Asthmatic Women Compared With Men.

Purpose: Gender differences exist in the prevalence of asthma and allergic diseases, partially due to the effects of sex hormones on the development of allergic manifestations. Women, compared with men, are more prone to suffer allergic asthma, experience difficulties in controlling asthma symptoms, and show adverse responses to drugs. However, there are knowledge gaps on the effectiveness of anti-leukotrienes drugs on lung function, symptoms, and pulmonary and systemic inflammation in adult asthmatic women compared with men. We conducted a prospective cohort study to characterize the effectiveness of an anti-leukotrienes drug, montelukast (MS), in asthmatic adult women and men. Methods: Twenty-one asthmatic subjects (11 women and 10 men), who were on low-dose inhaled corticosteroids (ICS), were treated with MS. The optimal control of the symptoms was achieved in both groups according to the Global Initiative for Asthma guidelines. At enrollment, and after 13 weeks from the beginning of MS, pulmonary function tests and asthma control tests were performed, and the fraction of exhaled nitric oxide and blood eosinophils levels were measured. Results: From baseline until the end of the study, women treated with MS + ICS had better control of the asthmatic symptoms, defined as higher asthma control test (ACT) score (17.00 ± 1.07 to 23.36 ± 0.45; p < 0.0015), improved pulmonary function [with higher forced expiratory volume in 1 s (from 77.25 ± 6.79 to 103.88 ± 6.24; p < 0.0077)], and forced vital capacity (from 91.95 ± 6.81 to 113.17 ± 4.79; p < 0.0183) compared with men. Interestingly, MS + ICS-treated women had significantly lower levels of blood eosinophils (from 5.27 ± 0.30 to 3.30 ± 0.31; p < 0.0449) and exhaled nitric oxide (from 44.70 ± 7.30 to 25.20 ± 3.90; p < 0.0294) compared with men. Conclusion: The treatment with MS, added to ICS, in women leads to better control of symptoms, better management of lung function, and decreased inflammation levels compared with ICS + MS treatment in men.

Simultaneous determination of levocetirizine dihydrochloride and montelukast sodium in human plasma by LC–MS/MS: development, validation, and application to a human pharmacokinetic study

Objectives A simple, rapid, selective, and sensitive high-performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the simultaneous determination of levocetirizine dihydrochloride and montelukast sodium in human plasma using fexofenadine hydrochloride as an internal standard. Method Liquid–liquid extraction of both drugs and internal standard from plasma into ethyl acetate was used for sample preparation and analysis. Separation of both drugs and internal standard was achieved on an Inertsil ODS-3 (4.6 mm × 50 cm, dp 5 μm, particle size) column using an isocratic mobile phase of acetonitrile and 10 mM ammonium formate adjusted to pH 8 with 50 μL ammonium hydroxide in composition of 73:27 (v/v) at a flow rate of 0.7 mL/min. The LC–MS/MS was operated under the multiple reaction monitoring mode (MRM) using an electrospray ionization technique. Mass parameters were optimized to monitor transitions at m/z [M + H]+ 389.0 → 200.8 for levocetirizine dihydrochloride, m/z [M + H]+ 586.2 → 422.2 for montelukast sodium, and m/z [M + H]+ 502.2 → 466.0 for fexofenadine hydrochloride. Results The method was found to be linear in the range of 1–500 ng/mL for both drugs. The intra-day and inter-day precision were in the range of 0.96–1.92% and 1.03–1.55%, respectively. Matrix effect was acceptable with %RSD &lt; 15. Conclusion The proposed method was validated and successfully applied for a pharmacokinetic study of both drugs in human plasma after oral administration of their pharmaceutical preparation.

Montelukast modifies simvastatin-induced myopathy and hepatotoxicity.

Montelukast (MNK) has prominent anti-inflammatory and antioxidant activities. It can protect the liver in different hepatotoxic models in animals. Simvastatin (SMV) is one of commonly used lipid lowering drugs for treatment of dyslipidemia in order to reduce cardiovascular disease. It has severe side effects such as myopathy and hepatotoxicity. The aim of the present study is to investigate the possible effect of MNK on SMV-induced myopathy and hepatotoxicity. Four groups of male rats: control group which received saline via stomach tube, MNK treated group (received 10 mg/kg/day MNK via stomach tube), SMV treated group (received 30 mg/kg/day SMV via stomach tube), and MNK + SMV (combination) group which received both MNK and SMV. All animals were treated for 14 days before obtaining blood and tissue samples. SMV has both hepatotoxic effects and myopathy. SMV caused a significant increase in myoglobin, creatinine kinase, ALT, AST, ALP, and bilirubin but, it decreased total proteins, globulin and albumin levels. Co-treatment of SMV and MNK increased the antioxidant activity significantly. MNK modifies partially the myopathic changes and hepatotoxic effect of SMV. Co-administration of MNK and SMV decreased their toxic potentials on the liver, skeletal muscles, and kidney. They have antioxidant activities when given together that produce muscle and hepatic protective effects.