Treprostinil administration using a metered dose inhaler

Abstract

Treprostinil can be administered using a metered dose inhaler. Such administration provides a greater degree of autonomy to patients. Also disclosed are kits that include a metered dose inhaler containing a pharmaceutical formulation containing treprostinil.

1 . A method for treating pulmonary hypertension, comprising administering to a subject in need thereof treprostinil or treprostinil derivative, or a pharmaceutically acceptable salt thereof by a metered dose inhaler. 
     
     
         2 . The method of  claim 1 , wherein said metered dose inhaler is a pressured metered dose inhaler. 
     
     
         3 . The method of  claim 1 , wherein said metered dose inhaler is a dry powder inhaler. 
     
     
         4 . The method of  claim 1 , wherein said metered dose inhaler is a soft mist inhaler. 
     
     
         5 . The method of  claim 4 , wherein said treprostinil is formulated in said inhaler as a solution, wherein a solvent of the solution comprises water, ethanol or a mixture thereof. 
     
     
         6 . The method of  claim 5 , wherein a concentration of the treprostinil in the solution ranges from about 500 μg/ml to about 2500 μg/ml. 
     
     
         7 . The method of  claim 6 , wherein the concentration of the treprostinil in the solution ranges from about 1000 μg/ml to about 2000 μg/ml. 
     
     
         8 . The method of  claim 1 , wherein a dose of the treprostinil administered during a single event ranges from about 15 μg to about 100 μg of the treprostinil. 
     
     
         9 . The method of  claim 8 , wherein the dose ranges from about 30 μg to about 90 μg of the treprostinil. 
     
     
         10 . The method of  claim 1 , wherein said administering does not have a systemic side effect on said subject, wherein the systemic side effect is selected from the group consisting of headache, flush, nausea, and dizziness. 
     
     
         11 . The method of  claim 1 , wherein said administering does not disrupt gas exchange in said subject. 
     
     
         12 . The method of  claim 1 , wherein said administering does change heart rate of said subject. 
     
     
         13 . The method of  claim 1 , wherein said administering does not affect systemic arterial pressure and systemic arterial resistance. 
     
     
         14 . The method of  claim 1 , wherein said administering comprises a limited number of breaths by said subject. 
     
     
         15 . The method of  claim 1 , wherein said administering lasts less than 5 minutes. 
     
     
         16 . The method of  claim 1 , wherein said administering lasts less than 1 minute. 
     
     
         17 . The method of  claim 1 , wherein said subject is a human being. 
     
     
         18 . The method of  claim 1 , further comprising administering to said subject at least one supplementary agent selected from the group consisting of diltiazem, amlodipine, nifedipine, sildenafil, tadalafil, vardenafil, bosentan, sitaxsentan, ambrisenatn, prostacyclin, iloprost, beraprost and pharmaceutically acceptable salts thereof. 
     
     
         19 . A method of delivering to a subject in need thereof a therapeutically effective amount of treprostinil, or treprostinil derivative or a pharmaceutically acceptable salt thereof comprising administering to the subject the therapeutically effective amount of the treprostinil or treprostinil derivative or a pharmaceutically acceptable salt thereof using a metered dose inhaler. 
     
     
         20 . The method of  claim 19 , wherein said metered dose inhaler is a pressured metered dose inhaler. 
     
     
         21 . The method of  claim 19 , wherein said metered dose inhaler is a dry powder inhaler. 
     
     
         22 . The method of  claim 19 , wherein said metered dose inhaler is a soft mist inhaler. 
     
     
         23 . The method of  claim 22 , wherein said treprostinil is formulated in the metered dose inhaler as a solution, wherein a solvent of the solution comprises water, ethanol or a mixture thereof. 
     
     
         24 . The method of  claim 23 , wherein a concentration of the treprostinil in the solution ranges from about 500 μg/ml to about 2500 μg/ml. 
     
     
         25 . The method of  claim 24 , wherein the concentration of the treprostinil in the solution ranges from about 1000 μg/ml to about 2000 μg/ml. 
     
     
         26 . The method of  claim 19 , wherein a dose of the treprostinil administered during a single event ranges from about 15 μg to about 100 μg of the treprostinil. 
     
     
         27 . The method of  claim 26 , wherein the dose ranges from about 30 μg to about 90 μg of the treprostinil. 
     
     
         28 . The method of  claim 19 , wherein said administering does not have a systemic side effect on said subject, wherein the systemic side effect is selected from the group consisting of headache, flush, nausea, and dizziness. 
     
     
         29 . The method of  claim 19 , wherein said administering does not disrupt gas exchange in said subject. 
     
     
         30 . The method of  claim 19 , wherein said administering does change heart rate of said subject. 
     
     
         31 . The method of  claim 19 , wherein said administering does not affect systemic arterial pressure and systemic arterial resistance. 
     
     
         32 . The method of  claim 19 , wherein said administering comprises a limited number of breaths by said subject. 
     
     
         33 . The method of  claim 19 , wherein said administering lasts less than 5 minutes. 
     
     
         34 . The method of  claim 19 , wherein said administering lasts less than 1 minute. 
     
     
         35 . The method of  claim 19 , wherein said subject is a human being. 
     
     
         36 . A kit for treating pulmonary hypertension, comprising (i) a metered dose inhaler containing a pharmaceutical formulation comprising treprostinil or treprostinil derivative, or a pharmaceutically acceptable salt thereof, and (ii) instructions for use of in treating pulmonary hypertension. 
     
     
         37 . The kit of  claim 36 , wherein said metered dose inhaler is a pressured metered dose inhaler. 
     
     
         38 . The kit of  claim 36 , wherein said metered dose inhaler is a dry powder inhaler. 
     
     
         39 . The kit of  claim 36 , wherein said metered dose inhaler is a soft mist inhaler. 
     
     
         40 . The kit of  claim 39 , wherein said formulation further comprises water, ethanol or a mixture thereof. 
     
     
         41 . The kit of  claim 36 , wherein a concentration of the treprostinil in said formulation is from about 500 μg/ml to about 2500 μg/ml. 
     
     
         42 . The kit of  claim 41 , wherein said concentration is from about 1000 μg/ml to about 2000 μg/ml. 
     
     
         43 . The kit of  claim 36 , further comprising an effective amount of at least one supplementary agent selected from the group consisting of diltiazem, amlodipine, nifedipine, sildenafil, tadalafil, vardenafil, bosentan, sitaxsentan, ambrisenatn, prostacyclin, iloprost, beraprost and pharmaceutically acceptable salts thereof. 
     
     
         44 . A kit comprising a metered dose inhaler containing a pharmaceutical formulation comprising treprostinil or treprostinil derivative, or a pharmaceutically acceptable salt thereof. 
     
     
         45 . The kit of  claim 44 , wherein said metered dose inhaler is a pressured metered dose inhaler. 
     
     
         46 . The kit of  claim 44 , wherein said metered dose inhaler is a dry powder inhaler. 
     
     
         47 . The kit of  claim 44 , wherein said metered dose inhaler is a soft mist inhaler. 
     
     
         48 . The kit of  claim 47 , wherein said formulation further comprises water, ethanol or a mixture thereof. 
     
     
         49 . The kit of  claim 44 , wherein a concentration of the treprostinil in said formulation is from about 500 μg/ml to about 2500 μg/ml. 
     
     
         50 . The kit of  claim 44 , wherein said concentration is from about 1000 μg/ml to about 2000 μg/ml. 
     
     
         51 . The kit of  claim 44 , further comprising instructions for using the metered dose inhaler for inhaling the treprostinil.