Source: Health Sciences Authority (SG) Revision Year: 2022 Publisher: Product Registrant: Organon Singapore Pte. Ltd., 150 Beach Road, #36-01/08 Gateway West, Singapore 189720 Zuellig Pharma (B) Sdn Bhd, Unit 5, 1st floor, Spg 607, Jalan Gadong, Kg Beribi, BSB, BE1118, Brunei ...
Mometasone furoate, a synthetic corticosteroid, exhibits anti-inflammatory, antipruritic and vasoconstrictive properties.
The pharmacologic profile of mometasone furoate was determined by standard laboratory methods. Relative to betamethasone valerate, anti-inflammatory activity and anti-psoriatic activity of mometasone furoate was 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 μg/ear) was equipotent to betamethasone valerate after single application, and was approximately eight times as potent as betamethasone valerate after five daily applications (ED50 = 0.002 μg/ear/day vs 0.014 μg/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 μg/ear/day) was less potent than betametasone valerate (ED50 = 3.1 μg/ear/day) in suppressing the HPA axis in mice after five daily application. In the thymolysis assay, mometasone furoate (ED50 = 26.6 μg/ear/day) was approximately two times as potent as betamethasone valerate (ED50 = 51.6 μg/ear/day) when applied topically, and following subcutaneous administration for five days, mometasone furoate (ED50 = 11.2 μg/mouse) was approximately six times as potent as betamethasone valerate (ED50 = 59.8 μg/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 indices 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.
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 μg/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 into 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.
The percutaneous absorption of mometasone furoate cream 0.1% was evaluated in subjects receiving a single application of radio-labeled 3H-mometasone furoate cream 0.1% which remained on intact skin for eight hours. Based on the amount of radioactivity excreted in the urine and feces during the five-day study period, approximately 0.4% of the applied dose was absorbed systematically. The radioactive content found in plasma and red blood cells remained a few counts above background levels (corresponding to <0.1 ng/ml) throughout the study.
Onset of action was investigated in several clinical trials with both pediatric and adult patients with various dermatologic conditions. A rapid onset of action with mometasone cream 0.1% was demonstrated after one week of treatment by percent improvement from baseline in total disease sign/symptom score (ranging from 25% to 81%). In these studies, percent improvement for the comparative agents were: betamethasone valerate (ranged from 43% to 81%), clobetasone butyrate (59%); hydrocortisone butyrate (54%); fluocinolone acetonide (24%); triamcinolone acetonide (36%); and for the vehicle alone (15% and 28%). Furthermore, in two of these studies, mometasone furoate cream 0.1% was significantly more effective than flucinolone acetonide (P <0.001) and hydrocortisone butyrate (P ≤0.05) at Day 4 evaluation.
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