Elomet Mechanism of Action

Mometasone furoate, a synthetic corticosteroid, exhibits anti-inflammatory, antipruritic and vasoconstrictive properties.
Pharmacology: Onset of Action: Mometasone furoate lotion 0.1% showed rapid onset of action after one treatment week in patients with scalp psoriasis. As demonstrated by results at Day 8 in one study, improvement in total sign/symptom scores was significantly (P<0.01) greater in mometasone-treated patients than in those treated with betamethasone valerate 0.1%.
Pharmacodynamics: Pre-Clinical Data: The pharmacologic profile of mometasone furoate was determined by standard laboratory methods. Relative to betamethasone valerate, the anti-inflammatory activity and anti-psoriatic activity of mometasone furoate were evaluated in mice and guinea pigs, respectively. Hypothalamic-pituitary-adrenal (HPA) axis suppression, thymolysis and skin atrophy were evaluated in mice.
In the croton oil assay in mice, mometasone furoate (ED₅₀ = 0.02 ug/ear) was equipotent to betamethasone valerate after single application, and was approximately eight times as potent as betamethasone valerate after five daily applications (ED₅₀ values = 0.002 ug/ear/day vs 0.014 ug/ear/day). In guinea pigs, mometasone furoate was approximately twice as potent as betamethasone valerate in reducing M. ovalis-induced epidermal acanthosis after 14 daily applications.
With respect to other pharmacologic activities commonly associated with corticosteroids, mometasone furoate (ED₅₀ = 5.3 ug/ear/day) was less potent than betamethasone valerate (ED₅₀ = 3.1 ug/ear/day) in suppressing the HPA axis in mice after five daily applications. In the thymolysis assay, mometasone furoate (ED₅₀ = -26.6 ug/ear/day) was approximately two times as potent as betamethasone valerate (ED₅₀ = 51.6 ug/ear/day) when applied topically, and following subcutaneous administration for five days, mometasone furoate (ED₅₀ = 11.2 ug/mouse) was approximately six times as potent as betamethasone valerate (ED₅₀ = 59.8 ug/mouse). At doses five to 5000 times the effective anti-inflammatory doses, mometasone furoate was three to eight times more potent than betamethasone valerate with respect to skin thinning in mice. Based on the ratio of systemic potency (HPA suppression or thymolysis) to topical anti-inflammatory potency, the therapeutic indexes for mometasone furoate were approximately three to ten times greater than those for the comparative, betamethasone valerate. Therefore, mometasone furoate would be expected to have a superior safety margin to that of betamethasone valerate.
Pharmacokinetics: Pre-Clinical Data: The percutaneous absorption and excretion of ³H-mometasone furoate cream and/or ointment was evaluated in rats, rabbits and dogs with doses ranging from 5.2 to 22 ug/cm². Additionally, the tissue distribution of absorbed radioactivity was determined in rabbits.
Systemic absorption of ³H-mometasone furoate was minimal in all species studied, ranging from approximately 2% in dogs to 6% in rabbits over a 5- to 7-day period. The cream and ointment formulations were comparable with respect to systemic absorption. Plasma levels were low ranging from <0.1 to <1 ng/ml. Less than 1.3% of the applied dose was excreted in urine of all species and from 1.5 to 4.2% was excreted in feces. Characterization of urinary metabolites was not possible due to the low levels of drug in urine. However, it is well known that corticosteroids are metabolized to inactive water-soluble substances such as sulfate esters or glucuronides and are excreted as such. In rabbits, there was no unusual accumulation of radioactivity in any tissue.
Human Pharmacokinetics: Due to the occlusive nature of the ointment base, the percutaneous absorption following application of a corticosteroid ointment is greater than that of a topical corticosteroid in a cream or lotion formulation. Consequently, absorption following application of mometasone furoate lotion 0.1% is expected to be no greater than that which may occur after application of the ointment formulation.