Methods and unit dose formulations for the inhalation administration of aminoglycoside antibiotics
A patient suffering from an endobronchial infection is treated by administering to the patient for inhalation a dose of less than about 4.0 ml of a nebulized aerosol formulation comprising from about 60 to about 200 mg/ml of an aminoglycoside antibiotic, such as tobramycin, in a physiologically acceptable carrier in a time period of less than about 10 minutes. Unit dose devices for storage and delivery of the aminoglycoside antibiotic formulations are also provided.
1. A method of the treatment of a cystic fibrosis patient having an endobronchial Pseudomonas aeruginosa infection comprising administering to the patient for inhalation a nebulized unit dose of 3.5 ml or less of an aqueous solution comprising an amount of tobramycin in a physiologically acceptable carrier effective to treat the Pseudomonas aeruginosa infection in the endobronchial space of the patient, for a duration of nebulization less than about 10 minutes, using a piezoelectric oscillator inhalation device having a rate of aerosol output of not less than about 4 μl/sec, that releases at least about 75% of the loaded dose, and that produces aerosol particles having particle sizes between about 1 μm to about 5 μm.
2. A method of claim 1 wherein the dose comprises 2.0 ml or less of the nebulized aerosol formulation.
3. A method of claim 1 wherein the dose comprises 1.5 ml or less of the nebulized aerosol formulation.
4. A method of claim 1 wherein the aerosol formulation comprises from about 80 to about 180 mg/ml of tobramycin.
5. A method of claim 1 wherein the aerosol formulation comprises from about 90 to about 150 mg/ml of tobramycin.
6. A method of claim 1 wherein the duration of nebulization is less that about 8 minutes.
7. A method of claim 1 wherein the duration of nebulization is less that about 6 minutes.
8. A method of claim 1 wherein the inhalation device has a rate of aerosol output of not less than about 5 μl/sec.
9. A method of claim 1 wherein the inhalation device has a rate of aerosol output of not less than about 8 μl/sec.
10. A method of claim 1 wherein the inhalation device releases at least about 80% of the loaded dose.
11. A method of claim 1 wherein the inhalation device releases at least about 85% of the loaded dose.
12. A method of claim 1 wherein the aerosol formulation comprises from about 60 to about 200 mg/ml of tobramycin.
13. A method of claim 12 wherein the aerosol formulation comprises from about 60 to about 150 mg/ml of tobramycin.
14. A method of claim 12 wherein the aerosol formulation comprises from about 60 to about 120 mg/ml of tobramycin.
15. A method of claim 12 wherein the aerosol formulation comprises from about 90 to about 150 mg/ml of tobramycin.
16. A method of claim 12 wherein the aerosol formulation comprises from about 90 to about 120 mg/ml of tobramycin.