Methods for the Treatment of Systemic Disorders Treatable with Mast Cell Stabilizers, including Mast Cell Related Disorders
Methods for the treatment of systemic disorders treatable with mast cell stabilizers, including mast cell related disorders, are provided.
1 . A method of treating a patient having a systemic mast cell related disorder comprising administering to the patient a composition comprising a mast cell stabilizer, wherein the bioavailability of the mast cell stabilizer is greater than about 5%, and wherein administration of the composition produces in a human subject group an average AUC (0-∞) of the mast cell stabilizer greater than about 120 ng*hr/mL and/or an average C max of the mast cell stabilizer greater than about 55 ng/mL.
2 . The method of claim 1 , wherein the mast cell stabilizer selected from cromolyn sodium, cromolyn lysinate, ammonium cromoglycate, magnesium cromoglycate, dihydropyridines such as nicardipine and nifedipine, lodoxamide, nedocromil, barnidipine, YC-114, elgodipine, niguldipine, ketotifen, methylxanthines, and quercetin.
3 . The method of claim 1 , wherein the composition is administered by a route selected from inhalation administration, oral administration, parenteral administration, subcutaneous administration, topical administration, buccal administration, nasal administration, rectal administration, vaginal administration, and sublingual administration.
4 . The method of claim 1 , wherein the composition is administered with a metered dose inhaler, nebulizer, soft mist inhaler, high efficiency nebulizer, or ultrasonic nebulizer.
5 . The method of claim 1 , wherein the composition is administered with a dry powder inhaler.
6 . The method of claim 4 , wherein the mast cell stabilizer is cromolyn sodium, and wherein the metered dose inhaler, nebulizer, soft mist inhaler, high efficiency nebulizer, or dry powder inhaler provides an RF (≦3.3 μm) of at least about 30% and/or an RF (≦5 μm) of at least about 65%.
7 . The method of claim 4 , wherein the mast cell stabilizer is cromolyn sodium, and wherein the metered dose inhaler, nebulizer, soft mist inhaler, high efficiency nebulizer, or dry powder inhaler provides an RF (≦3.3 μm) of at least about 45% and/or an RF (≦5 μm) of at least about 75%.
8 . The method of claim 1 , wherein the mast cell stabilizer is cromolyn sodium, and wherein administration of the composition produces in a human subject group an average AUC (0-∞) of the cromolyn sodium greater than about 120 ng*hr/mL and an average C max of the cromolyn sodium greater than about 55 ng/mL.
9 . (canceled)
10 . (canceled)
11 . The method of claim 4 , wherein the mast cell stabilizer is cromolyn sodium, and wherein the composition comprises greater than about 2% cromolyn sodium.
12 . The method of claim 4 , wherein the mast cell stabilizer is cromolyn sodium, and wherein the composition comprises about 4% to about 6% cromolyn sodium.
13 . The method of claim 12 , wherein the composition comprises one or more of purified water, sodium chloride, mannitol, and sodium EDTA.
14 . The method of claim 4 , wherein the composition has a fill volume of about 0.1 mL to about 5 mL.
15 . (canceled)
16 . The method of claim 4 , wherein the composition comprises about 1 mg to about 120 mg of cromolyn sodium.
17 . (canceled)
18 . (canceled)
19 . (canceled)
20 . The method of claim 4 , wherein the composition comprises about 40 mg of cromolyn sodium.
21 - 30 . (canceled)
31 . The method of claim 1 , wherein the systemic mast cell related disorder is selected from the group consisting of a mast cell activation syndrome; mastocytosis; idiopathic urticaria; chronic urticaria; atopic dermatitis; idiopathic anaphylaxis; Ig-E and non Ig-E mediated anaphylaxis; angioedema; allergic disorders; irritable bowel syndrome; mastocytic gastroenteritis; mastocytic colitis; fibromyalgia; kidney fibrosis; atherosclerosis; myocardial ischemia; hypertension; congestive heart failure; pruritus; chronic pruritus; pruritus secondary to chronic kidney failure; heart, vascular, intestinal, brain, kidney, liver, pancreas, muscle, bone and skin conditions associated with mast cells; CNS diseases such as Parkinson's disease and Alzheimer's disease; metabolic diseases such as diabetes; sickle cell disease; autism; chronic fatigue syndrome; lupus; chronic lyme disease; interstitial cystitis; multiple sclerosis; cancer; migraine headaches; psoriasis; eosinophilic esophagitis; eosinophilic gastroenteritis; Churg-Strauss syndrome; hypereosinophilic syndrome; eosinophilic fasciitis; eosinophilic gastrointestinal disorders; chronic idiopathic urticaria; myocarditis; Hirschsprung's-associated enterocolitis; postoperative ileus; wound healing; stroke; transient ischemic attack; pain; neuralgia; peripheral neuropathy; acute coronary syndromes; pancreatitis; cutaneous mastocytosis; systemic mastocytosis; indolent systemic mastocytosis; dermatomyositis; fibrotic skin diseases; pain associated with cancer; ulcerative colitis; inflammatory bowel disease; radiation colitis; celiac disease; gluten enteropathy; radiation cystitis; painful bladder syndrome; hepatitis; hepatic fibrosis; cirrhosis; rheumatoid arthritis; lupus erythematosus; and vasculitis.
32 . The method of claim 1 , wherein the systemic mast cell related disorder is irritable bowel syndrome.
33 . The method of claim 1 , wherein the systemic mast cell related disorder is painful bladder syndrome or interstitial cystitis.
34 . The method of claim 1 , wherein the systemic mast cell related disorder is a mast cell activation syndrome.
35 - 66 . (canceled)
67 . The method of claim 1 , wherein the mast cell stabilizer is cromolyn sodium, and wherein administration of the composition produces in a human subject group an average AUC (0-∞) of the cromolyn sodium greater than about 200 ng*hr/mL and an average C max of the cromolyn sodium greater than about 80 ng/mL.
68 . The method of claim 1 , wherein the mast cell stabilizer is cromolyn sodium, and wherein administration of the composition produces in a human subject group an average AUC (0-∞) of the cromolyn sodium greater than about 330 ng*hr/mL and an average C max of the cromolyn sodium greater than about 150 ng/mL.
69 . The method of claim 1 , wherein the mast cell stabilizer is cromolyn sodium, and wherein administration of the composition produces in a human subject group an average AUC (0-∞) of the cromolyn sodium greater than about 525 ng*hr/mL and an average C max of the cromolyn sodium greater than about 230 ng/mL.
70 - 78 . (canceled)
79 . The method of claim 1 , wherein administration of the composition does not cause one or more adverse events selected from the group consisting of dysgeusia and abdominal discomfort.
80 - 97 . (canceled)
98 . The method of claim 2 , wherein the composition is administered by a route selected from inhalation administration, oral administration, parenteral administration, subcutaneous administration, topical administration, buccal administration, nasal administration, rectal administration, vaginal administration, and sublingual administration.
99 . The method of claim 5 , wherein the mast cell stabilizer is cromolyn sodium, and wherein the metered dose inhaler, nebulizer, soft mist inhaler, high efficiency nebulizer, or dry powder inhaler provides an RF (≦3.3 μm) of at least about 30% and/or an RF (≦5 μm) of at least about 65%.
100 . The method of claim 5 , wherein the mast cell stabilizer is cromolyn sodium, and wherein the metered dose inhaler, nebulizer, soft mist inhaler, high efficiency nebulizer, or dry powder inhaler provides an RF (≦3.3 μm) of at least about 45% and/or an RF (≦5 μm) of at least about 75%.
101 . The method of claim 5 , wherein the composition comprises about 1 mg to about 120 mg of cromolyn sodium.
102 . The method of claim 5 , wherein the composition comprises about 40 mg of cromolyn sodium.