Methods and compositions for treating edema refractory to oral diuretics

1. A pharmaceutical composition comprising an aqueous solution of arginine bumetanide salt and one or more pharmaceutically acceptable excipients, wherein the aqueous solution comprises between about 4 mg/mL and about 15.0 mg/mL of the arginine bumetanide salt, and wherein the aqueous solution has a pH of between about 5 and about 9.

2. The pharmaceutical composition of claim 1 , wherein the aqueous solution has a pH of between about 6 and about 8.

3. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipients comprise a surfactant or a permeation enhancer.

4. The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically acceptable excipients comprise a buffering agent, a preservative, a viscosity enhancer, or a tonicity agent.

5. The pharmaceutical composition of claim 4 , wherein the one or more pharmaceutically acceptable excipients comprise a buffering agent.

6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for subcutaneous, sublingual, or intranasal administration.

7. A method of administering an aqueous solution of arginine bumetanide salt to a subject for treating edema, wherein the aqueous solution of arginine bumetanide salt comprises between about 4 mg/mL and about 15.0 mg/ml of the arginine bumetanide salt and one or more pharmaceutically acceptable excipients, and wherein the aqueous solution has a pH of between about 5 and about 9, and wherein a dose of a pharmaceutical composition comprising the arginine salt of bumetanide is administered intranasally, subcutaneously, or sublingually.

8. The method of claim 7 , wherein the administering comprises delivering a dose of from of from 25 μl to 250 μl of the pharmaceutical composition to the subject.

9. The method of claim 7 , wherein the method comprises subcutaneously administering the arginine bumetanide salt to the subject.

10. The method of claim 9 , wherein the method comprises subcutaneously administering from 100 μl to 300 μl of an aqueous solution of the arginine bumetanide salt to the subject.

11. The method of claim 7 , wherein the dose is delivered not more than from 1 to 4 times over a six hour period.

12. The method of claim 7 , wherein the subject:

a) is suffering from edema refractory to oral diuretics,

b) has congestive heart failure,

c) is suffering from edema in the lung,

d) has failed to achieve diuresis with oral diuretic therapy prior to the administering, optionally wherein at least one oral diuretic is selected from loop diuretics, such as bumetanide, furosemide or torsemide, or potassium-sparing diuretics, such as amiloride or spironolactone, or

e) is experiencing swelling of the legs, shortness of breath, difficulty breathing, reduced intestinal motility, or chest pain unresolved with oral diuretic therapy prior to the administering.

13. The method of claim 7 , wherein the subject does not receive more than a total of about 10 mg of the arginine bumetanide salt over a 12 hour period.

14. The method of claim 7 , wherein the subject's risk of hospitalization due to complications associated with edema is reduced.

15. The method of claim 7 , wherein the subject is a mammal, optionally wherein the subject is a dog or a human.