Sustained release of antiinfectives

Abstract

Provided, among other things, is a method of treating or ameliorating pulmonary infection in a cystic fibrosis patient comprising pulmonary administration of an effective amount of a liposomal/complexed antiinfective to the patient, wherein the (i) administrated amount is 50% or less of the comparative free drug amount, or (ii) the dosing is once a day or less, or (iii) both.

1 .- 25 . (canceled) 
     
     
         26 . A liposomal aminoglycoside formulation comprising an aminoglycoside or salt thereof encapsulated in liposomes, wherein the lipid component of the liposomes consists of a sterol and a phosphatidylcholine, and the weight ratio of the lipid component to aminoglycoside is less than 2.5 (lipid component) to 1 (aminoglycoside). 
     
     
         27 . The liposomal aminoglycoside formulation of  claim 26 , wherein the aminoglycoside is streptomycin, gentamicin, tobramycin, amikacin, netilmicin or kanamycin, or a salt thereof. 
     
     
         28 . The liposomal aminoglycoside formulation of  claim 26 , wherein the aminoglycoside is amikacin, or a salt thereof. 
     
     
         29 . The liposomal aminoglycoside formulation of  claim 28 , wherein the aminoglycoside or salt thereof is amikacin sulfate. 
     
     
         30 . The liposomal aminoglycoside formulation of  claim 26 , wherein the phosphatidylcholine is selected from the group consisting of egg phosphatidylcholine (EPC), soy phosphatidylcholine (SPC), hydrogenated egg phosphatidylcholine (HEPC), hydrogenated soy phosphatidylcholine (HSPC), dipalmitoyl phosphatidylcholine (DPPC), dioleoyl phosphatidylcholine (DOPC), dimyristoyl phosphatidylcholine (DMPC), distearoyl phosphatidylcholine (DSPC), palmitoylstearoyl phosphatidylcholine (PSPC), and mixtures thereof. 
     
     
         31 . The liposomal aminoglycoside formulation of  claim 26 , wherein the phosphatidylcholine is DPPC. 
     
     
         32 . The liposomal aminoglycoside formulation of  claim 26 , wherein the sterol is cholesterol. 
     
     
         33 . The liposomal aminoglycoside formulation of  claim 26 , wherein the sterol is cholesterol and the phosphatidylcholine is DPPC. 
     
     
         34 . The liposomal aminoglycoside formulation of  claim 28 , wherein the sterol is cholesterol and the phosphatidylcholine is DPPC. 
     
     
         35 . The liposomal aminoglycoside formulation of  claim 29 , wherein the sterol is cholesterol and the phosphatidylcholine is DPPC. 
     
     
         36 . A method of treating a mycobacterial infection in the lungs of a patient in need thereof, comprising administering to the lungs of the patient an effective amount of the formulation of claim  1 . 
     
     
         37 . The method of  claim 36 , wherein the aminoglycoside is streptomycin, gentamicin, tobramycin, amikacin, netilmicin or kanamycin, or a salt thereof. 
     
     
         38 . The method of  claim 36 , wherein the aminoglycoside is amikacin, or a salt thereof. 
     
     
         39 . The method of  claim 38 , wherein the aminoglycoside or salt thereof is amikacin sulfate. 
     
     
         40 . The method of  claim 36 , wherein the phosphatidylcholine is selected from the group consisting of egg phosphatidylcholine (EPC), soy phosphatidylcholine (SPC), hydrogenated egg phosphatidylcholine (HEPC), hydrogenated soy phosphatidylcholine (HSPC), dipalmitoyl phosphatidylcholine (DPPC), dioleoyl phosphatidylcholine (DOPC), dimyristoyl phosphatidylcholine (DMPC), distearoyl phosphatidylcholine (DSPC), palmitoylstearoyl phosphatidylcholine (PSPC), and mixtures thereof. 
     
     
         41 . The method of  claim 36 , wherein the phosphatidylcholine is DPPC. 
     
     
         42 . The method of  claim 36 , wherein the sterol is cholesterol. 
     
     
         43 . The method of  claim 38 , wherein the sterol is cholesterol and the phosphatidylcholine is DPPC. 
     
     
         44 . The method of  claim 39 , wherein the sterol is cholesterol and the phosphatidylcholine is DPPC. 
     
     
         45 . The method of  claim 36 , wherein administering to the lungs of the patient comprises inhalation administration via a nebulizer at a dosing schedule of once a day or less. 
     
     
         46 . The method of  claim 36 , wherein the mycobacterial infection is a  M. avium  complex ( M. avium  and  M. intracellulare ) infection.