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 receivedTNS 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.
RCT Entities:
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 CFpatients 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 CFpatients 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: Chris Stockmann; Jessica K Roberts; Venkata K Yellepeddi; Catherine M T Sherwin Journal: Clin Pharmacokinet Date: 2015-05 Impact factor: 6.447