title: Tolerability and Pharmacokinetic Evaluation of Inhaled Dry Powder Tobramycin Free Base in Non-Cystic Fibrosis Bronchiectasis Patients.
abstract: BACKGROUND
  Bronchiectasis is a 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.
  
  
  OBJECTIVE
  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 to participants with non-cystic fibrosis bronchiectasis. The free base and absence of excipients reduces the inhaled powder dose.
  
  
  METHODS
  Eight participants in the study were trained in handling the device and inhaling correctly. During drug administration the inspiratory flow curve 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.
  
  
  CONCLUSIONS
  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 site of infection.
  
  
  CONCLUSIONS
  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 dry powder device were well tolerated. Our data support further clinical studies to evaluate safety and efficacy of this compound in this population.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, the Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Hoppentocht
authors.affiliation: Department of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Onno W
authors.initials: OW
authors.lastname: Akkerman
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, the Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Hagedoorn
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Jan-Willem C
authors.initials: JW
authors.lastname: Alffenaar
authors.affiliation: Department of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.|Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Tjip S
authors.initials: TS
authors.lastname: van der Werf
authors.affiliation: Department of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Huib A M
authors.initials: HA
authors.lastname: Kerstjens
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, the Netherlands.
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, the Netherlands.
authors.forename: Anne H
authors.initials: AH
authors.lastname: de Boer
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D001987:Bronchiectasis / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology*; D003550:Cystic Fibrosis / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D058995:Dry Powder Inhalers; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D011208:Powders; D014031:Tobramycin / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D011208:Powders; D014031:Tobramycin