Effect of montelukast on polymorphonuclear leukocyte functions in asthmatic patients.

Cevikbas A.

Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Marmara, Tibbiye Caddesi No: 49 Haydarpasa, Istanbul 81010, Turkey. umran.gurer veezy.com

Leukotriene receptor antagonists are being used widely in the treatment of bronchial asthma. They have been shown to possess anti-inflammatory properties, but there is no sufficient data about their effects on polymorphonuclear leukocyte functions.The aim of this study was to investigate the effects of montelukast, a specific cysteinyl leukotriene-1 receptor antagonist, on human polymorphonuclear leukocyte (PMN) functions (phagocytic and intracellular killing activity) in asthmatic patients.Fifteen mild to moderate asthmatic patients were included in the study. They were treated with montelukast (10 mg/day per os) in addition to their previous medications for 2 weeks. Whole blood samples of patients were taken before and after this treatment period. Phagocytic activities and intracellular killing activities of polymorphonuclear leukocytes isolated from whole blood samples were tested by using appropriate technics.Phagocytic and intracellular killing activities of PMNs were significantly increased (p<0.001, p<0.05) by montelukast compared to those before treatment.These results show that montelukast has an enhancing effect on PMN functions in asthmatic patients.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12890423&dopt=Abstract montelukast, Singulair




[Preventive effects of montelukast on hypoxic pulmonary hypertension in rats]

[Article in Chinese]

Su Q.

Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.

OBJECTIVE: To evaluate the role of cysteinyl leukotriene(CysLT) in the pathogenesis of hypoxic pulmonary hypertension and the preventive effects of montelukast, a CysLT receptor antagonist, on hypoxic pulmonary hypertension. METHODS: Thirty male Wistar rats were randomly divided into three groups: control group, hypoxic group and montelukast preventive group. The animal model of pulmonary hypertension was established by exposing the rats to normabaric hypoxic conditions for 3 weeks. The thickness of pulmonary arterioles was measured by a computerized image analyzer. The level of LTC4 in plasma was measured by EIA. RESULTS: In the hypoxic group, the index of right ventricular hypertrophy[RV/(LV + S)] and the index of wall thickness of pulmonary arteriole (WT% and WA%) increased significantly when compared against those in the control group [RV/(LV + S): 30.85% +/- 1.44% vs 20.75% +/- 1.97%; WT%: 23.54% +/- 4.43% vs 13.17% +/- 3.67%; WA%: 72.76% +/- 9.28% vs 50.41% +/- 6.37%, P < 0.01, respectively]. Meanwhile, the plasma level of LTC4 in hypoxic rats was higher than that in control rats [(2395.40 +/- 193.86) pg/ml vs (1006.50 +/- 193.17) pg/ml, P < 0.01]. In the preventive group, the RV/(LV + S) (24.09% +/- 1.09%), WT% (15.44% +/- 4.72%) and WA% (51.98% +/- 12.18%) decreased remarkably as compared with those of the hypoxic group(P < 0.01). The plasma level of LTC4 in the preventive group (2706.25 +/- 350.49 pg/ml) was not significantly different from that in the hypoxic group(P > 0.05). CONCLUSION: Chronic hypoxia stimulates synthesis and release of LTC4. CysLT may play an important role in the pathogenesis of hypoxic pulmonary hypertension and montelukast can prevent hypoxi pulmonary hypertension.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12910720&dopt=Abstract montelukast, Singulair




Adherence to montelukast versus inhaled corticosteroids in children with asthma.

Ananthakrishnan M.

Department of Pediatrics, Madigan Army Medical Center, Tacoma, Washington, USA. edward.carter seattlechildrens.org

Our objective was to compare adherence to montelukast with adherence to inhaled corticosteroids (ICS) in children with persistent asthma. In this retrospective study, we obtained data from a computerized hospital pharmacy database and medical records on 14l patients, 3-18 years of age, who received care for asthma at a military medical center. For each patient, we collected fill/refill data from a consecutive 6-month period and calculated an adherence rate, i.e., (# doses filled/# doses prescribed) x 100. We then determined whether the patient had "good adherence" (adherence rate, > or =70%) or "very poor adherence" (adherence rate, <50%). Eighty-one children were prescribed montelukast, and 104 took ICS; 44 of these children took both. The majority of patients had mild or moderate persistent asthma. There was no significant difference between mean adherence rates: 71% (95% CI, 65-77%) for montelukast vs. 67% (95% CI, 61-73%) for ICS. Fifty-one percent of patients taking montelukast had good adherence, compared to 41% in the ICS group (P = 0.27). Nineteen percent of the montelukast group and 26% of the ICS group had very poor adherence (P = 0.31). Using pharmacy refill data, we found that children with asthma were no more likely to take montelukast than inhaled corticosteroids. Adherence to both medications was suboptimal, even in a system that provides free and easy access to medications. Published 2003 Wiley-Liss, Inc.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12950042&dopt=Abstract montelukast, Singulair




Outcomes of patients treated with fluticasone propionate or montelukast sodium.

Markson L.

Department of Epidemiology, Merck and Company, West Point, Pennsylvania, USA. felicia_ramey merck.com

The authors conducted a retrospective database study of patients with asthma (age range, 6-55 yr) who initiated fluticasone propionate or montelukast sodium treatment between an index period of July 1998 and June 1999. All patients were observed for 12 months before and after the index period. Changes in asthma-related hospitalizations, emergency department visits, oral corticosteroid use, and short-acting beta-agonist use were analyzed. The odds of postindex asthma-related events were estimated. In multivariate analysis, use of a short-acting beta agonist (SABA) was significantly associated with fluticasone treatment (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.21-2.26) and preindex use of SABAs (OR, 1.84; 95% CI, 1.34-2.53). In this managed care population, fluticasone and montelukast provided similar effectiveness.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12964550&dopt=Abstract montelukast, Singulair




A leukotriene receptor antagonist modulates iNOS in the lung and in a leukotriene-free cell model.

Madar Z.

Institute of Biochemistry, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, PO Box 12, 76100 Rehovot, Israel.

Nitric oxide (NO), an important cell signaling molecule, is considered a marker of inflammatory response and is elevated in asthmatics. This study investigated the effects of montelukast (a leukotriene receptor antagonist) on iNOS expression and activity in a Brown Norway (BN) rat allergic inflammation model and in L2 lung epithelial cells. Allergic inflammation was induced by ovalbumin (OVA) injection in BN rats followed by treatment with either montelukast or dexamethasone (DX). Allergen inhalation was performed, and post-allergen Penh was measured 5 min after the challenge. Cysteinyl leukotriene levels were measured in bronchoalveolar lavage (BAL) fluid and lung iNOS expression and activity determined. These parameters were also measured in cytokine stimulated L2 lung epithelial cells. iNOS expression was significantly higher in OVA challenged rats compared to the naive, DX, and montelukast treated groups, as confirmed by immunohistochemistry and Western blot analysis. However, no significant differences in NOS activity were found. Cysteinyl leukotriene measured in BAL was significantly higher in all OVA challenged rats compared to naive controls. Incubation of L2 cells with a mixture of interferon gamma (IFNgamma), lipopolysaccharide (LPS), and tumor necrosis factor (TNFalpha) resulted in high levels of nitrite formation resulting from iNOS induction. Treatment of cytokine stimulated cells with DX or montelukast significantly decreased iNOS expression and activity. No detectable cysteinyl leukotrienes were found in the supernatant fluid of L2 cells. This study confirms the ability of montelukast to modulate iNOS function and raises the possibility that changes in iNOS expression and activity may occur via pathways independent of cysteinyl leukotrienes.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14559427&dopt=Abstract montelukast, Singulair