Unit doses, aerosols, kits, and methods for treating heart conditions by pulmonary administration

Abstract

Methods of treating a heart condition include administering by inhalation an effective amount of at least one antiarrhythmic pharmaceutical agent to a patient in need thereof. Nebulized drug product and kits are also contemplated.

What is claimed is: 
     
         1 . A method of treating atrial arrhythmia comprising administering a pharmaceutical composition via inhalation to a subject in need thereof, said pharmaceutical composition comprising a therapeutically effective amount of an antiarrhythmic agent, wherein said antiarrhythmic agent is selected from the group consisting of: class I, class II, class III, and class IV antiarrhythmics, a salt and a solvate thereof, and any combination thereof, and wherein a concentration of said antiarrhythmic agent in said pharmaceutical composition is about 20 to about 60 mg/mL. 
     
     
         2 . The method of  claim 1 , wherein said therapeutically effective amount of said antiarrhythmic agent has a maximum ΔQRS of from about 1 to about 100 msec in said subject as measured by electrocardiography. 
     
     
         3 . The method of  claim 3 , wherein said maximum ΔQRS is from about 3 to about 20 msec. 
     
     
         4 . The method of  claim 1 , wherein said therapeutically effective amount of said antiarrhythmic agent has said maximum ΔQRS same as or greater than a maximum ΔQRS achieved by a second amount of said antiarrhythmic agent when administered intravenously to said subject as measured by electrocardiography, wherein said therapeutically effective amount is less than half of said second amount. 
     
     
         5 . The method of  claim 1 , wherein said concentration of said antiarrhythmic agent is about 30 to about 50 mg/mL. 
     
     
         6 . The method of  claim 1 , wherein said concentration of said antiarrhythmic agent is about 45 mg/mL. 
     
     
         7 . The method of  claim 1 , wherein said concentration of said antiarrhythmic agent is 45 mg/mL. 
     
     
         8 . The method of  claim 1 , wherein said pharmaceutical composition comprises about 60 to about 130 mg of said antiarrhythmic agent. 
     
     
         9 . The method of  claim 1 , wherein said therapeutically effective amount of said antiarrhythmic agent has a T max  of from about 0.2 to about 5 minutes in said subject. 
     
     
         10 . The method of  claim 1 , wherein said therapeutically effective amount of said antiarrhythmic agent has a C max  of from about 50 to about 1000 ng/mL in said subject. 
     
     
         11 . The method of  claim 1 , wherein said therapeutically effective amount of said antiarrhythmic agent has a AUC Last  of from about 100 to about 10000 hr*ng/mL in said subject. 
     
     
         12 . The method of  claim 11 , wherein said AUC Last  is from about 200 to about 2000 hr*ng/mL. 
     
     
         13 . The method of  claim 1 , wherein said therapeutically effective amount of said antiarrhythmic agent has a distribution t 1/2  of from about 0.1 to about 15 minutes in said subject. 
     
     
         14 . The method of  claim 13 , wherein said distribution t 1/2  is from about 3 to about 5 minutes. 
     
     
         15 . The method of  claim 1 , wherein said therapeutically effective amount of said antiarrhythmic agent has an elimination t 1/2  of from about 1 to about 25 hours in said subject. 
     
     
         16 . The method of  claim 15 , wherein said elimination t 1/2  is from about 8.5 to about 10.5 hours. 
     
     
         17 . The method of  claim 1 , wherein the administering comprises aerosolizing said pharmaceutical composition using a jet nebulizer. 
     
     
         18 . The method of  claim 17 , wherein said aerosolizing occurs at room temperature. 
     
     
         19 . The method of  claim 1 , wherein said administering is conducted via up to six inhalations. 
     
     
         20 . The method of  claim 1 , wherein said administering takes about 1 to about 10 min. 
     
     
         21 . The method of  claim 1 , wherein said pharmaceutical composition comprises an aerosol of said aerosolized antiarrhythmic agent that comprises particles having a mass median aerodynamic diameter less than 4 μm. 
     
     
         22 . The method of  claim 1 , wherein said therapeutically effective amount of said antiarrhythmic agent has an estimated total lung dose (eTLD) of about 30 to about 90 mg when administered to a subject via inhalation. 
     
     
         23 . The method of  claim 1 , wherein said antiarrhythmic agent comprises flecainide acetate. 
     
     
         24 . The method of  claim 1 , wherein said pharmaceutical composition further comprises a pH buffer prepared from acetic acid. 
     
     
         25 . The method of  claim 1 , wherein a pH of said pharmaceutical composition is from 5.0 to 6.5. 
     
     
         26 . The method of  claim 1 , wherein said pharmaceutical composition comprises a racemic mixture of flecainide. 
     
     
         27 . The method of  claim 1 , wherein said atrial arrhythmia comprises tachycardia. 
     
     
         28 . The method of  claim 27 , wherein said tachycardia is selected from the group consisting of: supraventricular tachycardia, paroxysmal supraventricular tachycardia, atrial fibrillation, paroxysmal atrial fibrillation, acute episodes in persistent and permanent atrial fibrillation, atrial flutter, paroxysmal atrial flutter, and lone atrial fibrillation.