RT Journal Article
SR Electronic
T1 Evaluation of inhaled dry powder tobramycin free base in non-cystic fibrosis bronchiectasis patients
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA2562
DO 10.1183/13993003.congress-2016.PA2562
VO 48
IS suppl 60
A1 Hoppentocht, Marcel
A1 Akkerman, Onno
A1 Hagedoorn, Paul
A1 Alffenaar, Jan-Willem
A1 van der Werf, Tjip
A1 Kerstjens, Huib
A1 Frijlink, Henderik
A1 de Boer, Anne
YR 2016
UL http://erj.ersjournals.com/content/48/suppl_60/PA2562.abstract
AB Bronchiectasis patients infected with P. aeruginosa require adequate treatment with antibiotics. The primary objectives of this study were to assess local tolerability and the pharmacokinetic parameters of inhaled excipient free dry powder tobramycin free base in this patient group.Escalating doses were administered with a new DPI (Cyclops) to eight participants with non-cystic fibrosis bronchiectasis who were trained in operating the inhaler correctly. During drug administration the inspiratory flow curve was recorded and several flow parameters were computed. Local tolerability was assessed by spirometry and recording adverse events. Pharmacokinetic parameters were computed from serum samples collected before, and 15, 30, 45, 60, 75, 90, 105, 120 min; 4, 8 and 12 h after inhalation.The free base of tobramycin was well tolerated and a good drug dose-serum concentration correlation was obtained. Relatively small inhaled volumes were computed from the recorded flow curves, resulting presumably in substantial deposition in the central airways – i.e., at the primary site of inflammation. Normalised maximum serum concentration (Cmax) increased with decreasing inhaled volume. We believe that this can be explained with an increased bronchial circulation in bronchiectasis patients from 1% to 30% of the cardiac output due to the inflammation. Because bronchiectasis is progressively deteriorating, accompanied by increased inflammation, it can be hypothesised that the higher blood circulation at a higher degree of inflammation increases the absorption rate of tobramycin from the site of deposition.Our data challenge to further investigate the effect of increased inflammation on the Cmax.