Aerosolized fluoroquinolones and uses thereof
View Patent ↗Disclosed herein are formulations of fluoroquinolones suitable for aerosolization and use of such formulations for aerosol administration of fluoroquinolone antimicrobials for the treatment of pulmonary bacterial infections. In particular, inhaled levofloxacin specifically formulated and delivered for bacterial infections of the lungs is described. Methods include inhalation protocols and manufacturing procedures for production and use of the compositions described.
1. A method of treating a bacterial infection in a patient having a chronic obstructive pulmonary disease, comprising administering an aerosol of a solution comprising levofloxacin or ofloxacin and a divalent or trivalent cation to a lung of the patient.
2. The method of claim 1 , wherein the solution comprises levofloxacin at a concentration from about 100 mM to about 625 mM and magnesium chloride at a concentration from about 125 mM to about 250 mM, has a pH from about 5.5 to about 6.5, and an osmolality from about 350 mOsmol/kg to about 750 mOsmol/kg.
3. The method of claim 1 , wherein the aerosol comprises a mass median aerodynamic diameter from about 2 microns to about 5 microns with a geometric standard deviation less than or equal to about 2.5 microns.
4. The method of claim 1 , wherein the aerosol comprises a mass median aerodynamic diameter from about 2.5 microns to about 4.5 microns with a geometric standard deviation less than or equal to about 1.8 microns.
5. The method of claim 1 , wherein the aerosol comprises a mass median aerodynamic diameter from about 2.8 microns to about 4.3 microns with a geometric standard deviation less than or equal to about 2 microns.
6. The method of claim 1 , comprising producing the aerosol with a vibrating mesh nebulizer.
7. The method of claim 6 , wherein the aerosol comprises a mass median aerodynamic diameter from about 2 microns to about 5 microns with a geometric standard deviation less than or equal to about 2.5 microns.
8. The method of claim 6 , wherein the aerosol comprises a mass median aerodynamic diameter from about 2.8 microns to about 4.3 microns with a geometric standard deviation less than or equal to about 2 microns.
9. The method of claim 6 , wherein the aerosol comprises a mass median aerodynamic diameter from about 2.5 microns to about 4.5 microns with a geometric standard deviation less than or equal to about 1.8 microns.
10. The method of claim 1 , wherein at least about 20 mg of levofloxacin or ofloxacin is administered to the lung.
11. The method of claim 1 , wherein at least about 100 mg of levofloxacin or ofloxacin is administered to the lung.
12. The method of claim 1 , wherein at least about 125 mg of levofloxacin or ofloxacin is administered to the lung.
13. The method of claim 1 , wherein at least about 150 mg of levofloxacin or ofloxacin is administered to the lung.
14. The method of claim 1 , wherein the aerosol is administered to the lung in less than about 10 minutes.
15. The method of claim 1 , wherein the aerosol is administered to the lung in less than about 5 minutes.
16. The method of claim 1 , wherein the aerosol is administered to the lung in less than about 3 minutes.
17. The method of claim 1 , wherein the aerosol is administered to the lung in less than about 2 minutes.
18. A method of treating a bacterial infection in a patient having cystic fibrosis, comprising administering an aerosol of a solution comprising levofloxacin or ofloxacin and a divalent or trivalent cation to a lung of the patient.
19. The method of claim 18 , wherein the solution comprises levofloxacin at a concentration from about 100 mM to about 625 mM and magnesium chloride at a concentration from about 125 mM to about 250 mM, has a pH from about 5.5 to about 6.5, and an osmolality from about 350 mOsmol/kg to about 750 mOsmol/kg.
20. The method of claim 18 , wherein the aerosol comprises a mass median aerodynamic diameter from about 2 microns to about 5 microns with a geometric standard deviation less than or equal to about 2.5 microns.
21. The method of claim 18 , wherein the aerosol comprises a mass median aerodynamic diameter from about 2.5 microns to about 4.5 microns with a geometric standard deviation less than or equal to about 1.8 microns.
22. The method of claim 18 , wherein the aerosol comprises a mass median aerodynamic diameter from about 2.8 microns to about 4.3 microns with a geometric standard deviation less than or equal to about 2 microns.
23. The method of claim 18 , comprising producing the aerosol with a vibrating mesh nebulizer.
24. The method of claim 23 , wherein the aerosol comprises a mass median aerodynamic diameter from about 2 microns to about 5 microns with a geometric standard deviation less than or equal to about 2.5 microns.
25. The method of claim 23 , wherein the aerosol comprises a mass median aerodynamic diameter from about 2.8 microns to about 4.3 microns with a geometric standard deviation less than or equal to about 2 microns.
26. The method of claim 23 , wherein the aerosol comprises a mass median aerodynamic diameter from about 2.5 microns to about 4.5 microns with a geometric standard deviation less than or equal to about 1.8 microns.
27. The method of claim 18 , wherein at least about 20 mg of levofloxacin or ofloxacin is administered to the lung.
28. The method of claim 18 , wherein at least about 100 mg of levofloxacin or ofloxacin is administered to the lung.
29. The method of claim 18 , wherein at least about 125 mg of levofloxacin or ofloxacin is administered to the lung.
30. The method of claim 18 , wherein at least about 150 mg of levofloxacin or ofloxacin is administered to the lung.
31. The method of claim 18 , wherein the aerosol is administered to the lung in less than about 10 minutes.
32. The method of claim 18 , wherein the aerosol is administered to the lung in less than about 5 minutes.
33. The method of claim 18 , wherein the aerosol is administered to the lung in less than about 3 minutes.
34. The method of claim 18 , wherein the aerosol is administered to the lung in less than about 2 minutes.
35. A method of treating a bacterial infection in a patient, comprising administering levofloxacin or ofloxacin to the patient to achieve a concentration in a lung of the patient of at least 32 μg/ml of levofloxacin or ofloxacin, wherein the levofloxacin or ofloxacin is administered as an aerosol comprising a divalent or trivalent cation.
36. The method of claim 35 , wherein the concentration achieved is at least 128 μg/ml of levofloxacin or ofloxacin.
37. The method of claim 35 , wherein the concentration achieved is at least 512 μg/ml of levofloxacin or ofloxacin.
38. The method of claim 35 , wherein the concentration achieved is from 800 μg/mL to 1600 μg/mL of levofloxacin or ofloxacin.
39. The method of claim 35 , wherein the aerosol comprises greater than about 50 mg/ml levofloxacin and magnesium chloride, has a pH from about 5.5 to about 6.5, and an osmolality from about 350 mOsmol/kg to about 750 mOsmol/kg.