185 Clinical pharmacology study of a new tobramycin solution for nebulisation

Aim: to characterise the in vitro and in vivo performance of Bramitob ®, a new tobramycin preservative-free sterile solution for nebulisation in comparison with ToN ® .Methods: in-vitro measurements, nebulisation time and the emitted dose, respirable dose, fine particle fraction and mass median aerodynamic diameter, were carried out using Pari Turbo Boy ® and Systam 290 LS ® nebulizers.The in vivo study was carried out as a single centre, single dose, randomised, double blind, twoway crossover study.Systemic exposure in plasma to assess the relative risk for systemic side effects and sputum levels as surrogate biomarker of activity were evaluated in nine CF patients after inhalation of Bramitob ® 300 rag/4 mL, or Tobi ® 300 rag/5 mL. Results:In vitro data demonstrated the equivalent performance of Bramitob ® and ToN ® with both nebulizers.In CF patients, tobramycin plasma levels peaked at 1.2 h (median) with Tobi ® and 1.5 h with Bramitob ®.Cmax and AUCoo (geometric mean) were 540ng/mL and 3454 ng*h/mL with Tobi ® and 549 ng/mL and 3470 ng*h/mL with Bramitob ®.Maximum tobramycin concentrations (543gg/g for ToN ® and 814gg/g for Bramitob ®) were observed in the first sputum sample taken 0.25 h after nebulisation.The target tobramycin sputum concentration of 400 gg/g was reached in eight patients with Bramitob ® and five patients with ToN ®.Conclusions: The in-vitro results demonstrates the similar performances of Bramitob ® and ToN ®.In the in vivo study, the systemic bioavailability of tobramycin was comparable with both formulations, whereas the peak concentration in sputum was higher with Bramitob ® than with ToN ®.