Changes in performance of the Pari eFlow rapid and Pari LC Plus during 6 months use by CF patients.

BACKGROUND: Nebulized antibiotics are important in the treatment of cystic fibrosis. The Pari eFlow rapid with vibrating mesh is often used off-label for the administration of tobramycin (TOBI) because of a reduced nebulization time and easier handling compared to a classic nebulizer-compressor combination. Mesh technology may be vulnerable, however. Therefore, we investigated particle size distribution and output as well as changes in the performance of the eFlow before and after 6 months of use, in comparison with the Pari LC Plus nebulizer plus Turboboy compressor. METHODS: Size distributions in the aerosols and nebulization times for TOBI were measured with laser diffraction technique; delivered doses by weighing. RESULTS: New eFlows produce considerably larger droplets (X(50) = 3.5 mum) from TOBI than new LC Plus nebulizers (X(50) = 2.8 mum). After use, the X(50) increases for both systems (to 3.7 and 3.3 mum, respectively). The relative span of the size distribution {(X(90)-X(10))/X(50)} changes from 1.26 to 1.28 mum for eFlow and from 2.19 to 2.45 mum for LC Plus. The total nebulization time doubles for LC Plus, whereas in 51% of all experiments the eFlow switched off after 10 min, resulting in incomplete dose delivery. For the eFlow, changes during use are related to clogging of orifices. Once being clogged, only replacement of the mesh restores the original performance. CONCLUSIONS: New eFlows produce larger droplets and in a narrower size range compared to new LC Plus nebulizers for TOBI, and therefore both devices are not equivalent. Theoretically a larger portion of the aerosol from eFlow is likely to be deposited in the upper airways. The performance of both tested nebulizers decreases after 6 months of use. For the eFlow, timely replacement of the mesh is necessary. These in vitro results underscore the importance of registration studies of new drug-device combinations.

Aerosolization of tobramycin (TOBI) with the PARI LC PLUS reusable nebulizer: which compressor to use? Comparison of the CR60 to the PortaNeb compressor.

Aerosol output, aerosol output rate, and aerosol size distribution are influenced by the compressed air flow rate through the nebulizer cup. Testing a nebulizer-compressor with a drug for inhalation in cystic fibrosis (CF) patients is mandatory prior to starting therapy. Tobramycin solution for inhalation (TSI), TOBI, is licensed in Europe with a recommendation for a "suitable" compressor connected to the PARI LC Plus nebulizer. To select a compressor, five devices were tested in a previous in vitro study and this resulted in a subsequent in vivo study. Two compressors [CR60 and PortaNeb (PN)] were compared in an open, randomized, crossover single dose pilot study in 10 CF patients to assess the most suitable device for inhalation of a tobramycin solution (TSI), TOBI, with the PARI LC Plus nebulizer. Lung function (FEV1 and FVC), pharmacokinetics [PK; safety (Cmax, Ctrough)], lung deposition (indirect method AUC0-6), nebulization time, and patients' experiences (questionnaire) were determined and compared. It was found that values of Cmax and AUC0-6 were higher with the CR60 than with the PortaNeb: 0.70 versus 0.54 mg/L, p = 0.005, and 2.54 versus 2.01 h.mg/L, p = 0.017, respectively. Tmax after use of the CR60 appeared earlier (0.64 vs. 0.85 h, p = 0.005). Transient airway narrowing was measured in three patients (2 x PN;1 x CR60) versus subjective chest tightness in seven patients (CR60 > PN). A shorter nebulization time for CR60 of 13.2 min compared to PN 16.1 min (p = 0.022) was observed, which was the main reason why patients preferred the CR60 (n = 7). No toxic serum levels were reached after inhalation of TSI. The CR60 compressor may seem advantageous based on a higher lung deposition and a shorter nebulization time, but a study in a large CF population to provide information on a possible higher risk of toxicity of TSI is called for.