Evaluation of Inhaled Dry Powder Tobramycin Free Base in Non-Cystic Fibrosis Bronchiectasis Patients

Marcel Hoppentocht, Onno W. Akkerman, Paul Hagedoorn, Jan-Willem C. Alffenaar, Tjip S. van der Werf, Huib A.M. Kerstjens, Henderik W. Frijlink, Anne H. de Boer

Bronchiectasis is a persistent condition characterised by dilated and thick-walled bronchi. The presence of Pseudomonas aeruginosa in bronchiectasis is associated with a higher hospitalisation frequency and a reduced quality of life, requiring frequent and adequate treatment with antibiotics.
To assess local tolerability and the pharmacokinetic parameters of inhaled excipient free dry powder tobramycin as free base administered with the Cyclops dry powder inhaler (DPI) to patients with non-cystic fibrosis bronchiectasis. The free base and absence of excipients reduce the inhaled powder dose.
Eight participants in the study were trained in handling the device and inhaling correctly. During drug administration the inspiratory flow profile was recorded. Local tolerability was assessed by spirometry and recording adverse events. Serum samples were collected before and 15, 30, 45, 60, 75, 90, 105, 120 min; 4, 8 and 12 h after inhalation respectively.
Dry powder tobramycin base was well tolerated and mild tobramycin-related cough was reported only once. A good drug dose – serum concentration correlation was obtained. Relatively small inhaled volumes were computed from the recorded flow curves, resulting in presumably substantial deposition in the central airways – i.e., at the main site of infection.
In this first study of inhaled dry powder tobramycin free base in non-cystic fibrosis bronchiectasis patients, the free base of tobramycin and the administration with the Cyclops DPI were well tolerated and appreciated. Our data invite further clinical studies to evaluate safety and efficacy of this compound in this patient population.

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