Mometasone Furoate

Indications

Mometasone furoate is a versatile therapeutic agent utilized for various conditions depending on the mode of administration. When administered as an inhaled therapy, it serves as a prophylactic measure against asthma for patients aged four years and older. For topical application in the form of an ointment, it is indicated for treating dermatitis and pruritus in patients over the age of two. The nasal spray form of mometasone furoate is available both over-the-counter and by prescription. The OTC nasal spray is indicated for managing upper respiratory allergic symptoms in individuals two years and older. Prescription formulations help in treating chronic rhinosinusitis with nasal polyps in adults aged 18 years and above, and for the prevention of seasonal allergic rhinitis in those aged 12 and older. Additionally, it is approved in combination with olopatadine for treating seasonal allergic rhinitis symptoms in patients aged 12 years and above.

Pharmacodynamics

Mometasone furoate is a synthetic corticosteroid that exhibits potent anti-inflammatory properties by engaging with glucocorticoid receptors. It is noted for having a glucocorticoid receptor affinity markedly higher-22 times-than that of dexamethasone. It also demonstrates lower affinity for mineralocorticoid receptors compared to naturally occurring corticosteroids, enhancing its selectivity. Mometasone furoate effectively diffuses through cell membranes, initiating various anti-inflammatory pathways and processes.

Absorption

The pharmacokinetic profile of mometasone furoate reveals a mean time to peak plasma concentration ranging from 1.0 to 2.5 hours post-administration. Its systemic bioavailability is quite low, recorded at less than 1%, although studies involving repeated dosing of inhaled corticosteroids have shown a possible increase in bioavailability to approximately 11%. Furthermore, the 0.1% ointment formulation is associated with a bioavailability of about 0.7%.

Metabolism

The metabolism of mometasone furoate primarily occurs in the liver, facilitated by the cytochrome P450 3A4 system. This metabolic process results in several metabolites, including free mometasone and 6-beta-hydroxy-mometasone furoate. These metabolic transformations are crucial for the eventual inactivation and elimination of the drug from the system.

Mechanism of Action

Mometasone furoate operates through a well-defined mechanism, primarily involving the inhibition of inflammatory cells and mediators within the body. Upon administration, corticosteroids such as mometasone furoate traverse cell membranes and enter the cytosol, where they engage with glucocorticoid receptors. Remarkably, mometasone furoate exhibits an affinity for these receptors that is 22 times greater than that of dexamethasone. This interaction prompts conformational alterations in the receptor, resulting in its detachment from associated chaperones and subsequent translocation to the cell nucleus. Within the nucleus, the receptors dimerize and bind to specific DNA sequences known as glucocorticoid response elements. This binding modulates gene expression by either enhancing the production of anti-inflammatory molecules or suppressing the synthesis of pro-inflammatory substances such as interleukins 4 and 5. Furthermore, mometasone furoate mitigates inflammation by inhibiting key transcription factors, including activator protein-1 and nuclear factor kappa B (NF-kappaB). In the context of asthma, mometasone furoate is believed to exert its effects by inhibiting key immune cells such as mast cells, eosinophils, basophils, and lymphocytes, along with reducing the activity of histamine, leukotrienes, and various cytokines.