Pharmaceutical compositions comprising nitroxyl donors
The present disclosure provides nitroxyl donating pharmaceutical compositions comprising N-substituted hydroxylamine derivatives. The compositions are highly efficacious in treating cardiovascular diseases (e.g., heart failure), have a suitable toxicological profile, and are sufficiently stable for intravenous or oral administration.
1. A method of treating heart failure, comprising intravenously administering to a human patient a nitroxyl donor composition comprising a compound of the formula (1):
wherein said composition is administered at a pH of from about 5 to about 6.5 and at a dose of about 1 μg/kg/min to about 30 μg/kg/min.
2. The method of claim 1 , wherein the composition is administered at a pH of from about 5.5 to about 6.
3. The method of claim 1 , wherein the composition is administered at a pH of about 6.
4. The method of claim 1 , wherein the composition further comprises a stabilizing agent.
5. The method of claim 4 , wherein the stabilizing agent is a cyclodextrin.
6. The method of claim 5 , wherein the cyclodextrin is a β-cyclodextrin.
7. A method of treating acute decompensated heart failure, comprising intravenously administering to a human patient a nitroxyl donor composition comprising a compound of the formula (1):
wherein said composition is administered at a pH of from about 5 to about 6.5 and at a dose of about 1 μg/kg/min to about 30 μg/kg/min.
8. The method of claim 7 , wherein the composition is administered at a pH of from about 5.5 to about 6.
9. The method of claim 7 , wherein the composition is administered at a pH of about 6.
10. The method of claim 7 , wherein the composition further comprises a stabilizing agent.
11. The method of claim 10 , wherein the stabilizing agent is a cyclodextrin.
12. The method of claim 11 , wherein the cyclodextrin is a β-cyclodextrin.
13. The method of claim 1 , wherein the composition is administered at a dose of at least 2.5 μg/kg/min.
14. The method of claim 1 , wherein the composition is administered in an amount of at least 5 μg/kg/min.
15. The method of claim 1 , wherein the composition is administered at a dose of at least 7.5 μg/kg/min.
16. The method of claim 1 , wherein the composition is administered at a dose of at least 12 μg/kg/min.
17. The method of claim 1 , wherein the composition is administered at a dose of at least 15 μg/kg/min.
18. The method of claim 7 , wherein the composition is administered at a dose of at least 2.5 μg/kg/min.
19. The method of claim 7 , wherein the composition is administered in an amount of at least 5 μg/kg/min.
20. The method of claim 7 , wherein the composition is administered at a dose of at least 7.5 μg/kg/min.
21. The method of claim 7 , wherein the composition is administered at a dose of at least 12 μg/kg/min.
22. The method of claim 7 , wherein the composition is administered at a dose of at least 15 μg/kg/min.