Rapid pulmonary delivery of inhaled tobramycin for Pseudomonas infection in cystic fibrosis: a pilot project.
BACKGROUND
Patients with cystic fibrosis spend as much 30 min a day inhaling tobramycin. Could a new rapid system deposit the equivalent amount of tobramycin faster?


METHODS
Six healthy adult males inhaled 5 ml (300 mg) of tobramycin from a breath enhanced nebulizer and either 125 mg (n = 3) or 150 mg (n = 3) from a vibrating membrane system with a large or small aerosol mixing chamber respectively. A radiolabel was added to the solution and shown to "track" with the tobramycin. Imaging was done with a dual headed gamma camera. Because the radiolabel will be cleared by mucociliary action during administration, algorithms were developed to allow the comparison of a slower system to a faster one.


RESULTS
Both formulations were well tolerated. The lung deposition was 16.6 +/- 3.2% (mean +/- SD) of the charge dose delivered in 10.9 +/- 1.0 min for the breath enhanced nebulizer versus 32.0 +/- 5.1% delivered in 2.5 +/- 0.4 min from the vibrating membrane system. The absolute pulmonary delivery of tobramycin was 49.9 +/- 9.6 versus 43.9 +/- 4.8 mg for the two systems respectively, differences that were statistically significant (pair t-test) but unlikely to be clinically significant. There was a similar deposition of tobramycin for the 125 and 150 mg dose.


CONCLUSIONS
It is possible to deliver an equivalent amount of tobramycin in a shorter period of time with the new vibrating membrane system and a more concentrated formulation. These data will allow the design of a comparison in patients with CF.
Coates
Allan L
AL
Division of Nuclear Medicine, Hospital for Sick Children Research Institute, University of Toronto, Toronto, Canada. allan.coates@sickkids.ca
Green
Maria
M
Leung
Kitty
K
Chan
Jeffrey
J
Ribeiro
Nancy
N
Louca
Emily
E
Ratjen
Felix
F
Charron
Martin
M
Tservistas
Markus
M
Keller
Manfred
M
D000280:Administration, Inhalation; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000382:microbiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D010865:Pilot Projects; D011552:Pseudomonas Infections / Q000188:drug therapy*; D013997:Time Factors; D014031:Tobramycin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D014031:Tobramycin