Glamont, 4 mg 28 pcs.

Pharmacotherapeutic group: Anti-inflammatory antibronchoconstrictor agent – leukotriene receptor blocker.

ATC code: R03DC03

Pharmacological characteristics

Pharmacodynamics
. Cysteinyl-leukotrienes (LTC4, LTD4, LTE4) are strong inflammatory mediators, eicosanoids, that are secreted by various cells, including mast cells and eosinophils. These important proasthmatic mediators bind to cysteinyl-leukotriene receptors. Cysteinyl-leukotriene type 1 receptors (CysLT1 receptors) are present in human airways (including bronchial smooth muscle cells, macrophages) and other proinflammatory cells (including eosinophils and some
myeloid stem cells). Cysteinyl leukotrienes correlate with the pathophysiology of bronchial asthma and allergic rhinitis. In asthma, leukotriene-mediated effects include bronchospasm, increased mucus secretion, increased vascular permeability
and increased eosinophil counts. In allergic rhinitis, after allergen exposure, cysteinyl leukotrienes are released from pro-inflammatory cells of the nasal mucosa during the early and late phases of the allergic reaction, which manifests as symptoms of allergic rhinitis. An intranasal test with cysteinyl-leukotrienes demonstrated increased nasal airway resistance and symptoms of nasal obstruction.
Montelukast is a highly active oral medication that significantly improves inflammation scores in bronchial asthma. According to biochemical and pharmacological analysis, montelukast binds with high affinity and selectivity to CysLT1 receptors without interacting with other pharmacologically important receptors in the airways (such as prostaglandin, cholinergic or β-adrenergic receptors). Montelukast inhibits the physiologic action of cysteinyl leukotrienes LTC4, LTD4, and LTE4 by binding to CysLT1 receptors without having a stimulatory effect on these receptors.
Montelukast inhibits CysLT1 receptors in the airways, as evidenced by its ability to block the development of bronchospasm in response to inhaled LTD4 in patients with bronchial asthma. A dose of 5 mg is sufficient to relieve bronchospasm induced by
LTD4.
Montelukast causes bronchodilation within 2 hours of oral administration and may enhance bronchodilation induced by β2-adrenomimetics.

Pharmacokinetics
Assimilation
Montelukast is rapidly and almost completely absorbed after oral administration. In adult patients, after ingestion of chewable tablets at a dose of 5 mg on an empty stomach, the maximum plasma concentration (Cmax) is reached after 2 hours. The average value of bioavailability is 73%. After chewable tablets in a dose of 4 mg on an empty stomach in patients aged 2 to 5 years Cmax is reached in 2 hours.

Distribution
Binding of montelukast to plasma proteins is more than 99%. The volume of distribution at equilibrium averages 8-11 liters. Preclinical studies have shown minimal penetration of montelukast through the blood-brain barrier. Twenty-four hours after administration, the concentration of montelukast is minimal in other tissues as well.

Metabolism
Montelukast is actively metabolized in the liver. When used in therapeutic doses, plasma concentrations of metabolites of montelukast are not determined in equilibrium in adults and children.
In vitro studies have shown that cytochrome P450 CYP isoenzymes (3A4, 2A6, 2C8 and 2C9) are involved in the metabolism of montelukast, while in therapeutic concentrations montelukast does not inhibit cytochrome P450 CYP isoenzymes: 3A4, 2C9, 1A2,
2A6, 2C19 and 2D6. Metabolites have insignificant therapeutic effect of montelukast.

Elimation
Plasma clearance of montelukast in healthy adult volunteers averages 45 ml/min. After ingestion of radioactively labeled montelukast, 86% of it is excreted through the intestine within 5 days and less than 0.2% through the kidneys, confirming that montelukast and its metabolites are excreted almost exclusively with bile.
The half-life of montelukast in young healthy adults is 2.7 to 5.5 hours. Pharmacokinetics of montelukast remains almost linear when administered orally in doses over 50 mg. When taking montelukast in the morning and evening hours
no differences in pharmacokinetics are observed. When taking 10 mg of montelukast once a day a moderate (about 14%) cumulation of the active substance in plasma is observed.

Peculiarities of the pharmacokinetics of montelukast in different groups of patients

Gender
The pharmacokinetics of montelukast in men and women are similar.

Elderly patients
With a single oral administration of 10 mg of montelukast, the pharmacokinetic profile and bioavailability are similar in elderly and younger patients. The plasma elimination half-life of montelukast is somewhat longer in the elderly. Dose adjustment of the drug in
elderly people is not required.

Race
No differences in clinically significant pharmacokinetic effects were found in patients of different races.

Hepatic impairment
. In patients with mild to moderate hepatic impairment and clinical manifestations of liver cirrhosis, a slowing of montelukast metabolism was noted, accompanied by an increase in the area under the pharmacokinetic concentration-time curve (AUC) of approximately 41% after a single dose of 10 mg.
The half-life of montelukast in these patients is slightly longer compared to healthy volunteers (mean half-life – 7.4 hours).
No change in the dose of montelukast for patients with mild to moderate hepatic impairment is required. There are no data on the nature of pharmacokinetics of montelukast in patients with severe hepatic impairment (more than 9 points on the Child-Pugh scale).

Renal insufficiency
Since montelukast and its metabolites are virtually not excreted through the kidneys, the pharmacokinetics of montelukast in patients with renal insufficiency have not been evaluated.
Adjustment of the drug dose for this group of patients is not required.