Chemical formula: C₂₇H₃₀Cl₂O₆ Molecular mass: 427.361 g/mol PubChem compound: 441335
Μometasone is a topical glucocorticoid with local anti-inflammatory properties.
It is likely that much of the mechanism for the effects of mometasone lies in its ability to inhibit the release of mediators of the inflammatory cascade.In vitro, mometasone inhibits the release of leukotrienes from leukocytes of allergic patients. In cell culture, mometasone demonstrated high potency in inhibition of synthesis and release of IL-1, IL-5, IL-6, and TNF-alpha; it is also a potent inhibitor of LT production and in addition it is an extremely potent inhibitor of the production of the Th2 cytokines, IL-4 and IL-5, from human CD4+ T-cells.
Μometasone has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor which is approximately 12 times that of dexamethasone, 7 times that of triamcinolone acetonide, 5 times that of budesonide, and 1.5 times that of fluticasone.
In a clinical trial, inhaled mometasone has been shown to reduce airway reactivity to adenosine monophosphate in hyperreactive patients. In another trial, pretreatment using inhaled mometasone for five days significantly attenuated the early and late phase reactions following inhaled allergen challenge and also reduced allergen-induced hyperresponsiveness to methacholine.
Inhaled mometasone treatment was also shown to attenuate the increase in inflammatory cells (total and activated eosinophils) in induced sputum following allergen and methacholine challenge. The clinical significance of these findings is not known.
In studies utilising nasal antigen challenge, mometasone nasal spray has shown anti-inflammatory activity in both the early- and late- phase allergic responses. This has been demonstrated by decreases (vs placebo) in histamine and eosinophil activity and reductions (vs baseline) in eosinophils, neutrophils, and epithelial cell adhesion proteins.
In 28% of the patients with seasonal allergic rhinitis, mometasone nasal spray demonstrated a clinically significant onset of action within 12 hours after the first dose. The median (50%) onset time of relief was 35.9 hours.
Μometasone exhibits marked anti-inflammatory activity and marked anti-psoriatic activity in standard animal predictive models.
In the croton oil assay in mice, mometasone was equipotent to betamethasone valerate after single application and about 8 times as potent after five applications.
In guinea pigs, mometasone was approximately twice as potent as betamethasone valerate in reducing m.ovalis-induced epidermal acanthosis (i.e. anti-psoriatic activity) after 14 applications.
The systemic bioavailability of mometasone following oral inhalation in healthy volunteers is low, due to poor absorption from the lungs and the gut and extensive pre-systemic metabolism. Plasma concentrations of mometasone following inhalation at the recommended doses of 200 micrograms to 400 micrograms per day were generally near or below the limit of quantification (50 pg/ml) of the analytical assay and were highly variable.
Μometasone, administered as an aqueous nasal spray, has a systemic bioavailability of <1% in plasma, using a sensitive assay with a lower quantitation limit of 0.25 pg/ml.
After intravenous bolus administration, the Vd is 332 l. The in vitro protein binding for mometasone is high, 98% to 99% in concentration range of 5 to 500 ng/ml.
Not applicable as mometasone is poorly absorbed via the nasal route.
The portion of an inhaled mometasone dose that is swallowed and absorbed in the gastrointestinal tract undergoes extensive metabolism to multiple metabolites. There are no major metabolites detectable in plasma. In human liver microsomes, mometasone is metabolised by cytochrome P-450 3A4 (CYP3A4).
The small amount that may be swallowed and absorbed undergoes extensive first-pass hepatic metabolism.
After intravenous bolus administration, mometasone has a terminal elimination T1/2 of approximately 4.5 hours. A radiolabelled, orally inhaled dose is excreted mainly in the feces (74%) and to a lesser extent in the urine (8%).
Absorbed mometasone is extensively metabolized and the metabolites are excreted in urine and bile.
Pharmacokinetic studies have indicated that systemic absorption following topical application of mometasone cream 0.1% is minimal, approximately 0.4% of the applied dose in man, the majority of which is excreted within 72 hours following application. Characterisation of metabolites was not feasible owing to the small amounts present in plasma and excreta.
Adverse reactions not observed in clinical studies, but seen in animals at exposure levels similar to clinical exposure levels and with possible relevance to clinical use were as follows.
No toxicological effects unique to mometasone exposure were demonstrated. All observed effects are typical of this class of compounds and are related to exaggerated pharmacologic effects of glucocorticoids.
Like other glucocorticoids, mometasone is a teratogen in rodents and rabbits. Effects noted were umbilical hernia in rats, cleft palate in mice, and gall bladder agenesis, umbilical hernia, and flexed front paws in rabbits. There were also reductions in maternal body weight gains, effects on fetal growth (lower fetal body weight and/or delayed ossification) in rats, rabbits and mice, and reduced offspring survival in mice.
Preclinical studies demonstrate that mometasone is devoid of androgenic, antiandrogenic, estrogenic or antiestrogenic activity but, like other glucocorticoids, it exhibits some antiuterotrophic activity and delays vaginal opening in animal models at high oral doses of 56 mg/kg/day and 280 mg/kg/day.
Like other glucocorticoids, mometasone showed a clastogenic potential in-vitro at high concentrations. However, no mutagenic effects can be expected at therapeutically relevant doses.
In studies of reproductive function, subcutaneous mometasone, at 15 micrograms/kg prolonged gestation and prolonged and difficult labour occurred with a reduction in offspring survival and body weight or body weight gain. There was no effect on fertility.
Μometasone is excreted in low doses in the milk of suckling rats.
The carcinogenicity potential of inhaled mometasone (aerosol with CFC propellant and surfactant) at concentrations of 0.25 to 2.0 micrograms/l was investigated in 24-month studies in mice and rats. Typical glucocorticoid-related effects, including several non-neoplastic lesions, were observed. No statistically significant dose-response relationship was detected for any of the tumour types.
Μometasone showed no genotoxic activity in a standard battery of in vitro and in vivo tests.
No further data.
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