UNIT DOSES, AEROSOLS, KITS, AND METHODS FOR TREATING HEART CONDITIONS BY PULMONARY ADMINISTRATION
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.
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.