Efficacy of montelukast in the treatment of chronic obstructive pulmonary disease in five horses

Abstract

Five horses with moderate to severe chronic obstructive pulmonary disease (COPD) were treated with 0.11 (0.01) mg/kg bodyweight of montelukast, a cysteinyl leukotriene receptor antagonist, once a day for 26 days. The horses were evaluated clinically and endoscopically and subjected to arterial blood gas analysis and lung function tests before and after the period of treatment, and the plasma concentrations of montelukast were determined by high-performance liquid chromatography with fluorescence detection. The treatment did not result in statistically significant differences in the total scores of clinical and endoscopical signs, or in the difference in the arterioalveolar partial pressure of oxygen, maximal changes in pleural pressure, pulmonary resistance or dynamic compliance. The mean (sd) peak plasma concentration (C(max0) of montelukast was 12 (4) ng/ml and was reached 66 (13) minutes (t(max)) after its oral administration. The dose of montelukast per kg bodyweight was approximately the same as that for human beings, but the C(max) in the horses was 28 times lower and the t(max) was reached in one-fifth of the time, suggesting that its oral bioavailability may be lower.

Modeling asthma: Pitfalls, promises, and the road ahead

“…Of specific interest, several compounds effective in rodent models of allergic airways disease (e.g. PDE4 inhibitors, cysteinyl leukotriene antagonists) were found to be ineffective as therapy for both RAO and human asthma, suggesting that horses might be an appropriate model to inform selection of therapies for trials in humans …”

“…PDE4 inhibitors, cysteinyl leukotriene antagonists) were found to be ineffective as therapy for both RAO and human asthma, suggesting that horses might be an appropriate model to inform selection of therapies for trials in humans. 97,98 The study of asthma in horses has several advantages including the ability to perform serial bronchoscopies and tissue biopsies in sedated, standing animals and determination of lung volumes by spirometry, both measurements that are impractical in rodents. Endobronchial ultrasound is another technique that can provide a relatively noninvasive measurement of ASM mass in horses with RAO.…”

Recurrent airway obstruction: A review

“…Although pretreatment with this drug failed to cause a significant reduction in neutrophilic airway inflammation, a reduction in the severity of airway obstruction was observed in a proportion of horses . In contrast, the oral administration of the cystseinyl leucotriene antagonist, montelukast, failed to show any therapeutic efficacy in RAO horses during disease exacerbation, although this may have reflected its low oral bioavailability compared with man . However, the leucotriene (LT) D4 receptor antagonist L‐708,738, despite having good orally bioavailability, also failed to show any therapeutic efficacy in symptomatic RAO horses .…”

Skin Immune System and Allergic Skin Diseases

“…Maturation of erythroid progenitor cell tumor growth; synergistic with IL-3 for mast cell growth IL-10 Downregulation (inhibits production of IL-1, IL-2, IL-4, IL-5, IL-5, IL-8, IL-12, TNF-a, IFN-g, MHC class II expression) IL- 11 Megakaryocyte, lymphocyte, and plasma cell growth IL- 12 Cytotoxic lymphocyte maturation; NK cell activation and proliferation IL- 13 Similar to IL-4; enhances production of MHC class II and integrins; reduced production of IL-1 and TNF; activation of eosinophils IL- 14 Expands clones of B-cells and suppresses immunoglobulin secretion IL -15 Proliferation; increased cytotoxicity of T-cells, NK cells; expression of ICAM-3; B-cell growth and differentiation IL- 16 Chemoattractant, growth factor IL- 17 Autocrine proliferation and activation IL- 18 Similar to IL-12; inhibits IgE production by increasing IFN-g Colony-Stimulating Factors Granulocyte CSF Neutrophil growth Monocyte CSF Monocyte growth Granulocyte-monocyte CSF Monomyelocytic growth Basic fibroblast growth factor (bFGF)…”