Methods of using dipivefrin

Abstract

The disclosure provides a method for systemic delivery of a therapeutically effective amount of epinephrine to a subject comprising orally administering dipivefrin or a dipivefrin salt to the subject. The disclosure also includes a method of treatment of a disease amenable to treatment by in vivo delivery of systemic epinephrine comprising administering dipivefrin or a dipivefrin salt to a subject in need of in vivo delivery of systemic epinephrine. The disease can be a respiratory disorder, anaphylaxis, cancer, or a microbial infection. The disclosure also includes dipivefrin or dipivefrin HCl orally dissolving tablets.

1 . (canceled) 
     
     
         2 . A method for treating a condition responsive to epinephrine in a subject comprising orally administering a therapeutically effective amount of dipivefrin or a pharmaceutically acceptable salt thereof to the subject. 
     
     
         3 . The method of  claim 2 , wherein the condition is a breathing difficulty. 
     
     
         4 . The method of  claim 3 , wherein the breathing difficulty is anaphylaxis, asthma, bronchitis, emphysema, croup, or a respiratory infection. 
     
     
         5 - 7 . (canceled) 
     
     
         8 . The method of  claim 2 , wherein the condition is cancer. 
     
     
         9 . The method of  claim 8 , wherein the cancer is skin cancer, brain cancer, a glioma, a sarcoma, breast cancer, lung cancer, non-small-cell lung cancer, mesothelioma, appendiceal cancer, a genitourinary cancer, a renal cell carcinoma, prostate cancer, bladder cancer, testicular cancer, penile cancer, cervical cancer, ovarian cancer, von Hippel Lindau disease, a head and neck cancer, a gastrointestinal cancer, a hepatocellular carcinoma, gallbladder cancer, esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer, a neuroendocrine tumor, a thyroid tumor, a pituitary tumor, an adrenal tumor, a hematological malignancy, a lymphoma, a leukemia, or a combination thereof. 
     
     
         10 - 11 . (canceled) 
     
     
         12 . The method of  claim 2 , wherein the condition is a microbial infection. 
     
     
         13 . The method of  claim 12 , wherein the microbial infection is a bacterial, viral, fungal, or parasitic infection. 
     
     
         14 - 19 . (canceled) 
     
     
         20 . The method of  claim 2 , wherein the dipivefrin is racemic dipivefrin. 
     
     
         21 - 22 . (canceled) 
     
     
         23 . The method of any one of  claim 2 , wherein L-dipivefrin hydrochloride is administered. 
     
     
         24 - 25 . (canceled) 
     
     
         26 . The method of  claim 2 , wherein the dipivefrin or salt thereof is administered as an oral aqueous solution. 
     
     
         27 . The method of  claim 2 , wherein the dipivefrin or salt thereof is administered as an orally dissolving tablet an orally disintegrating tablet. 
     
     
         28 . The method of any one of  claim 2 , wherein the dipivefrin or salt thereof is administered as a dosage form comprising 0.01 mg to 150 mg, 0.01 mg to 100 mg, 0.01 mg to 50 mg, 0.1 mg to 20 mg, 0.1 mg to 10 mg, 0.1 mg to 5 mg, 0.1 mg to 3 mg, 2.5 mg, 2 mg, or 1.5 mg dipivefrin. 
     
     
         29 . The method of  claim 2 , wherein the therapeutically effective amount of dipivefrin or salt thereof is an amount sufficient to provide an epinephrine plasma C max  of 0.1 to 50.0 ng/mL in the subject. 
     
     
         30 . The method of  claim 2 , wherein the therapeutically effective amount of dipivefrin or salt thereof is an amount sufficient to provide a pharmacokinetic profile substantially equivalent to the epinephrine pharmacokinetic profile of an US FDA-approved injectable dosage form comprising epinephrine, when the US FDA-approved injectable dosage form is administered either intramuscularly or subcutaneously, and the US FDA-approved dosage form comprises 0.3 mg epinephrine and is administered intramuscularly. 
     
     
         31 - 36 . (canceled) 
     
     
         37 . The method of  claim 2 , wherein the method provides a therapeutically effective amount of epinephrine within 30 minutes of administration, within 15 minutes of administration, within 10 minutes of administration, or within 5 minutes of administration. 
     
     
         38 . The method of  claim 2 , wherein the method provides a T max  of epinephrine within 45 minutes of administration. 
     
     
         39 . An orally dissolving tablet comprising dipivefrin or a dipivefrin salt in a matrix capable of dissolving in the oral cavity in 2 minutes or less. 
     
     
         40 . The tablet of  claim 39 , wherein the tablet comprises dipivefrin HCl. 
     
     
         41 . The tablet of  claim 39 , wherein the tablet additionally comprises a water soluble polymer and a sweetener. 
     
     
         42 . The tablet of  claim 41 , wherein the water soluble polymer is gelatin, HPMC, or a combination of the foregoing.