Comparison of two tobramycin nebuliser solutions: pharmacokinetic, efficacy and safety profiles of T100 and TNS

Abstract

Background: Tobramycin inhalation is an accepted treatment of chronic pseudomonal infection in cystic fibrosis (CF) patients. Twice daily inhalation is efficacious, but time-consuming.

Methods: In this randomized, open-label, multicentre, two-period, crossover study, 58 patients with CF and chronic Pseudomonas aeruginosa (PA) infection received two tobramycin nebuliser solutions: T100/eFlow or TNS/PARI LC PLUS. The primary objective was to demonstrate the equivalence of both treatments with respect to pharmacokinetics (area under the concentration-time curve and maximum concentration in plasma). Secondary endpoints were tobramycin sputum pharmacokinetics, reduction in PA colony forming units, improvement of lung function, incidence of adverse drug reactions and reduction of inhalation times.

Results: Tobramycin plasma AUC and Cmax were lower after administration of T100 than after TNS. The study failed to demonstrate systemic bioequivalence of the two treatments. After T100 administration, tobramycin sputum AUC and Cmax achieved higher values than after TNS. Changes in efficacy parameters from baseline were similar. Safety profiles were not different or unexpected. Inhalation time per inhalation was shorter during treatment with T100.

Conclusion: The lower systemic drug burden and the higher local drug deposition together with a comparable efficacy/safety profile and a shorter inhalation time render T100/eFlow an attractive treatment option for CF patients. (www.controlled-trials.com/ISRCTN85410458).

Keywords: Chronic Pseudomonas aeruginosa infection; Cystic fibrosis; Inhalation time; Pharmacokinetics; Tobramycin nebuliser solution.