PT  - JOURNAL ARTICLE
AU  - Hoppentocht, Marcel
AU  - Akkerman, Onno
AU  - Hagedoorn, Paul
AU  - Alffenaar, Jan-Willem
AU  - van der Werf, Tjip
AU  - Kerstjens, Huib
AU  - Frijlink, Henderik
AU  - de Boer, Anne
TI  - Evaluation of inhaled dry powder tobramycin free base in non-cystic fibrosis bronchiectasis patients
AID  - 10.1183/13993003.congress-2016.PA2562
DP  - 2016 Sep 01
TA  - European Respiratory Journal
PG  - PA2562
VI  - 48
IP  - suppl 60
4099  - http://erj.ersjournals.com/content/48/suppl_60/PA2562.short
4100  - http://erj.ersjournals.com/content/48/suppl_60/PA2562.full
SO  - Eur Respir J2016 Sep 01; 48
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.