title: Pharmacokinetic and tolerability profiles of tobramycin nebuliser solution 300 mg/4 ml administered by PARI eFlow(®) rapid and PARI LC Plus(®) nebulisers in cystic fibrosis patients.
abstract: BACKGROUND
  Tobramycin nebuliser solution (TNS) is indicated for maintenance therapy in cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa (PA) infections. Adherence to recommended therapy in CF has always been a challenge and new generation nebulisers are increasingly used "off label" to reduce the time required for inhalation, potentially improving patient compliance.
  
  
  METHODS
  In this open-label, randomised, multi-centre, two-period crossover study, 27 CF patients with PA infection received TNS 300 mg/4 mL (TNS4) via the PARI eFlow(®) rapid or PARI LC Plus(®) nebuliser twice daily for 28 days in two study periods separated by a 4-week washout. The pharmacokinetic profile in plasma and sputum were determined after single and multiple dose administration on Day 1 and Day 28, respectively. Nebulisation times and general safety and tolerability profiles were evaluated throughout the study.
  
  
  RESULTS
  Plasma tobramycin pharmacokinetic profiles were similar for the eFlow and LC Plus nebulisers both on Day 1 and Day 28. After multiple dose administration for 28 days, the eFlow/LC Plus ratio of geometric means for plasma C(max) and AUC(0-t), were 85.32 (90% CI, 61.24-118.86) and 87.44 (90% CI, 64.87-117.87), respectively. Despite the high variability, sputum tobramycin C(max) and AUC(0-t) for the eFlow on Day 28 tended to be higher than for the LC Plus (90% CI for the ratio, 86.11-226.45 and 81.81-236.71), respectively. Nebulisation times were significantly shorter for the eFlow with a median time for nebulisation of 5 min in comparison to 13 min for the LC Plus. Safety data confirmed a favourable safety profile for TNS4, with the majority of the findings being related to the underlying CF disease.
  
  
  CONCLUSIONS
  Plasma and sputum pharmacokinetic data in CF patients with chronic PA infection support comparable pulmonary delivery and safety of TNS4 administered using different nebulisers, with a significantly shorter nebulisation time for the eFlow.
authors.affiliation: Chiesi Farmaceutici S.p.A., Via Palermo, 26/A, 43100 Parma, Italy. m.govoni@chiesi.com
authors.forename: Mirco
authors.initials: M
authors.lastname: Govoni
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Poli
authors.forename: Daniela
authors.initials: D
authors.lastname: Acerbi
authors.forename: Debora
authors.initials: D
authors.lastname: Santoro
authors.forename: Helen
authors.initials: H
authors.lastname: Cicirello
authors.forename: Ottavia
authors.initials: O
authors.lastname: Annoni
authors.forename: Jozef
authors.initials: J
authors.lastname: Ružička
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011552:Pseudomonas Infections / Q000188:drug therapy*; D013183:Sputum / Q000378:metabolism; D014031:Tobramycin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D014031:Tobramycin