DERMAL INDICATIONS / HUMAN PATIENTS
Norketotifen (NK) is an Oral and Topical Drug for Atopic Dermatitis (Eczema) and for Pruritus (itch)
MECHANISMS OF ACTION STUDIES
As a dermal anti-inflammatory mast cell stabilizer, NK potently inhibits the release of specific pro-inflammatory cytokines for example TNFa, IL-4 and IL-13
Topical concentrations of NK to be applied on the skin of AD-patients have been found to express antimicrobial effects against strains of dermal bacteria, molds and fungi.
As previously described for ketotifen, NK was found to be free from immune-suppression in preclinical studies by Bridge Pharma.
As an antipruritic drug, NK potently inhibits both histaminic and non-histaminic pruritus.
NK is a potent drug and in preclinical studies, anti-inflammatory and anti-pruritic potencies of NK exceeded the potencies of the glucocorticoid prednisone, the potent and selective histamine H-4 inhibitor JNJ7777120, the potent JAK-inhibitor oclacitinib and the potent PDE4 inhibitor crisaborole.
PROOF OF CONCEPT STUDIES (Dermal Disorders):
NK is the active and long-acting metabolite of ketotifen which has been used by AD-patients for over 40 years. Numerous studies of ketotifen have been published by independent investigators and by investigators from the manufacturer (Sandoz/Novartis). Millions of doses of the prodrug ketotifen have been administered to patients suffering from dermal diseases (atopic dermatitis; pruritus). Doses of ketotifen greater than 1.0 mg, bid are not used since higher doses of ketotifen will cause unacceptable sedation. One milligram of ketotifen is rapidly metabolized in the liver and about 0.5 mg NK is formed. The therapeutic activity in patients after ketotifen administration is due to the active and long-acting metabolite NK, not to the poorly active, short-acting and severely sedating prodrug.
BRIDGE PHARMA, Inc.
Sarasota, FL 34242