Dorota Sands1, Ewa Sapiejka2, Grzegorz Gąszczyk3, Henryk Mazurek4. 1. Instytut Matki i Dziecka (IMiDz), ul. Kasprzaka 17a, 01-211 Warszawa, Poland. Electronic address: dorotasands@rubikon.pl. 2. Specjalistyczny Zespół Opieki Zdrowotnej nad Matką i Dzieckiem w Gdańsku, ul. Polanki 119, 80-308 Gdańsk-Oliwa, Poland. 3. Centrum Pulmonologii i Alergologii w Karpaczu S.A., ul. Myśliwska 13, 58-540 Karpacz, Poland. 4. Klinika Pneumonologii i Mukowiscydozy IGiChP, ul. Prof. J. Rudnika 3 B, 34-700 Rabka-Zdrój, Poland.
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 twotobramycin 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).
RCT Entities:
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).
Authors: Chris Stockmann; Jessica K Roberts; Venkata K Yellepeddi; Catherine M T Sherwin Journal: Clin Pharmacokinet Date: 2015-05 Impact factor: 6.447