Rapid pulmonary delivery of inhaled tobramycin for Pseudomonas infection in cystic fibrosis: a pilot project.

Abstract

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.

• Authors: Allan L Coates, Maria Green, Kitty Leung, Jeffrey Chan, Nancy Ribeiro, Emily Louca, Felix Ratjen, Martin Charron, Markus Tservistas, Manfred Keller
• Journal: Pediatric pulmonology (Pediatr Pulmonol) Vol. 43 Issue 8 Pg. 753-9 (Aug 2008) ISSN: 1099-0496 [Electronic] United States
• PMID: 18613006 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2008 Wiley-Liss, Inc.

Chemical References

• Anti-Bacterial Agents
• Tobramycin

Topics

• Administration, Inhalation
• Adult
• Anti-Bacterial Agents (administration & dosage, pharmacokinetics)
• Cystic Fibrosis (drug therapy, microbiology)
• Humans
• Male
• Middle Aged
• Nebulizers and Vaporizers
• Pilot Projects
• Pseudomonas Infections (drug therapy)
• Time Factors
• Tobramycin (administration & dosage, pharmacokinetics)
• Treatment Outcome