Clinical Pharmacology Study of Bramitob, a Tobramycin Solution for Nebulization, in Comparison with Tobi.

Background and objectives: To compare in vitro characteristics and pharmacokinetics of Bramitob®, a preservative-free tobramycin solution for nebulization, and Tobi® in patients with cystic fibrosis (CF) and Pseudomonas aeruginosa infection. Methods: In vitro characteristics of Bramitob® and Tobi® were evaluated using Pari TurboBoy™/LC Plus® and the Systam 290 LS™ nebulizers. In the randomized, double-blind, two-way crossover pharmacokinetic study, 11 patients with CF received a single nebulized dose (300mg) of Bramitob® or Tobi®, separated by a 7-day washout period. Plasma and sputum tobramycin concentrations were measured immediately before and over 24 hours after administration. Results: Bramitob® and Tobi® performed alike during nebulization. The fine particle fraction was 33–37% and the mass median aerodynamic diameter was <5μm. Nine patients completed the pharmacokinetic study. Tobramycin plasma profiles after administration of Bramitob® or Tobi® were similar, with a peak at 90 and 72 minutes after inhalation of Bramitob® and Tobi®, respectively. The elimination half-life was ∼5 hours for both products. The relative bioavailability of Bramitob® to Tobi® was 1.01, indicating comparable systemic exposure. Peak sputum concentration of tobramycin was 816 ± 681 μg/g for Tobi® and 1289 ± 851 μg/g for Bramitob® and was >400 μg/g (threshold sufficient for an antibacterial effect against P. aeruginosa) in 5 out of 9 patients receiving Tobi® and 8 out of 9 patients receiving Bramitob®. All adverse events were considered mild and judged not related to the study drugs. Conclusions: In vitro performance of Bramitob® was similar when nebulized with Pari TurboBoy™/LC Plus® and Systam 290 LS™ nebulizers and comparable to that of Tobi®. The systemic bioavailability of tobramycin was similar after administration of either Bramitob® or Tobi®; however, in sputum samples the tobramycin peak concentration was slightly greater after administration of Bramitob® than after Tobi®. [ABSTRACT FROM AUTHOR]