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Poor adherence to recommended therapy in cystic fibrosis (CF) is often because of the time demands of therapy. Tobramycin (TOBI®, 300 mg at 60 mg/ml) inhaled from the PARI LC PLUS® nebulizer requires about 20 min. This study determined if equivalent levels of pulmonary deposition could be achieved in shorter time using 1.5 ml of 100 mg/ml tobramycin solution delivered by an investigational eFlow® nebulizer. Sixteen males with stable CF, 8 children and 8 adults, and an FEV(1)  > 45% predicted inhaled both preparations on two occasions with (99m) Tc-DTPA added to the tobramycin. Blood samples were taken for quantification of tobramycin in the serum. The PARI LC PLUS® delivered 45.4 (39.3-51.6), mean and 95% CI, mg to the lungs in 17.0 ± 2.5 min (mean ± SD) with serum levels of 1,089 ± 388 µg/L. The investigational eFlow® delivered 46.3(40.3-51.7) mg in 4.0 ± 1.0 min with blood levels of 909 ± 458 µg/L. Only the time of delivery was significantly different with P < 0.0001 (paired t-test). Tolerability of the treatment was comparable for both inhalation regimes, but the shorter treatment was preferred by all patients. These results demonstrate the possibility of delivering equivalent levels of tobramycin much faster into the lungs of CF patients when using eFlow®, a very efficient electronic nebulizer., (Copyright © 2010 Wiley-Liss, Inc.)

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., ((c) 2008 Wiley-Liss, Inc.)

In quantifying aerosol delivery, the drug is often mixed with a radiolabel such as (99m)Tc-DTPA whose deposition is used as a proxy for the drug. (99m)Tc-DTPA deposited in the lung is cleared by a combination of absorption into the pulmonary circulation and mucociliary clearance. If administration is not instantaneous, the image will not include that clearance during administration, a problem raised if comparing devices with different administration times. However, if rates of clearance are measured, it will be possible to "correct" the initial image for the clearance that occurred during administration and before counting. Five adult males inhaled a 5-mL solution containing (99m)Tc-DTPA from a breath enhanced jet nebulizer (LC Plus)over the course of 10 min and a 1.25-mL solution from a vibrating membrane device (eFlow), which was delivered in 2.5 min. Quality assurance was the radioactivity count balance (RCB) defined as the difference in the total radioactivity pre-nebulization less post, divided by pre, and expressed as a percentage. Attenuation calculations used a (57)Co flood source (Macey and Marshall). The "correction" for the clearance of (99m)Tc-DTPA was 0.91 +/- 0.04 (mean +/- SD) for the LC Plus) and 0.96 +/- 0.02 for the eFlow). RCB was -0.6 +/- 3.5% for the LC Plus and -4.7 +/- 6.4% for the eFlow, implying acceptable accuracy. For the LC Plus, lung deposition was 15.9(13.4, 18.4)% (mean and 95% CI) of the charge dose, and for the eFlow it was 32.0(29.0, 35.0)%. This technique gave an acceptable level of accuracy for quantitative planar imaging and allowed the comparison of delivery from devices with very different rates of delivery.