title: Aerosolization of tobramycin (TOBI) with the PARI LC PLUS reusable nebulizer: which compressor to use? Comparison of the CR60 to the PortaNeb compressor.
abstract: 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.
authors.affiliation: Apotheek Haagse Ziekenhuizen, The Hague, The Netherlands., Adult cystic fibrosis Centre, Haga Teaching Hospital, The Hague, The Netherlands.
authors.forename: Elsbeth M
authors.initials: EM
authors.lastname: Westerman
authors.forename: Anne H De
authors.initials: AH
authors.lastname: Boer
authors.forename: Daan J
authors.initials: DJ
authors.lastname: Touw
authors.forename: Paul P H Le
authors.initials: PP
authors.lastname: Brun
authors.forename: Albert C
authors.initials: AC
authors.lastname: Roldaan
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.forename: Harry G M
authors.initials: HG
authors.lastname: Heijerman