mometasone

Mometasone is a potent synthetic corticosteroid with antiinflammatory, antipruritic, and vasoconstrictive properties. It has been used in the treatment of allergic rhinitis; topical dermatological disorders

as well as mild-tomoderate persistent asthma [Articles:18721246, 18681494, 18343239, 19618993].

PK:

Mometasone furoate administered as a nasal spray (Nasonex) has minimal systemic absorption. A large proportion of intranasally administered drug is quickly cleared from the nose into the throat and

Swallowed and absorbed. Studies have shown that the amount of mometasone furoate which is swallowed and absorbed undergoes extensive hepatic metabolism into multiple metabolites [Article:16251254]. CYP3A4 was found to be the major enzyme involved in the in-vitro 6 beta-hydroxylation of mometasone [Article:12831504]. The absorbed drug is excreted as metabolites mostly via the bile, and to a limited extent, into the urine.

PD:

Mometasone is a glucocorticoid agonist. It binds with high affinity to glucocorticoid receptor (GR/NR3C1) [Articles:9793625, 8439518] and translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The glucocorticoid receptor can act as both a transcription factor and as a regulator of other transcription factors such as NF-kappa B and AP-1 [Article:12859444]. It regulates the expression of a large number of target genes that affects inflammatory responses, cellular proliferation and differentiation in target tissues. The mechanism of action of glucocorticoid agonist is depicted in the Pharmacodynamics view of Glucocorticoid and Inflammatory genes pathway (http://www.pharmgkb.org/search/pathway/glucocorticoid/pharmacodynamics.jsp).

Studies have shown that mometasone effectively inhibited AP-1 and NF-kappaB (RELA/NFKB1) activities and RANTES/CCL5 production [Article:12859444]. Mometasone furoate also decreased adhesion molecule (ICAM1, ICAM2) expression in psoriasis patients treated with mometasone [Article:9729054] as well as VCAM1 expression in human bronchial epithelial cells [Article:10100995]. Suppression of adhesion molecule expression may contribute to its anti-inflammatory effect.