Influence of inhalation mode on aerosol lung deposition in patients with cystic fibrosis PART 1:Pharmacokinetic data as representative of lung deposition

Objectives: To investigate the impact of two different inhalation flow maneuvers (TIM = slow and deep inhalation and TBM = normal tidal breathing) on aerosol lung deposition in patients with CF using pharmacokinetic parameters as a representation of lung deposition. Methods: Randomized, open-label, cross-over study. The study group consisted of 18 adult patients with a confirmed diagnosis of CF (genetic analysis). Each patient inhaled a tobramycin solution twice during separate study visits: once in TIM and the other time in TBM mode. Blood samples were collected in order to model tobramycin pharmacokinetics. Outcome measurements: Relative bioavailability (Frel) of tobramycin is defined as the ratio of AUCTIM to AUCTBM, in which the AUC represents the plasma concentration area under the curves. A ratio greater than 1 indicates higher lung deposition for TIM compared to TBM. Individual pharmacokinetic parameters were calculated and assimilated with patient tobramycin serum values using a computerized CF-based Bayesian population model (MW-Pharm, Mediware). Results: Frel was 1 or greater for all patients (mean = 1.55, sd = 0.39, 95%CI = 1.37-1.73). In addition, mean Frel was significant higher than the value of 1 (mean difference = 0.55,