PMID- 17352404
OWN - NLM
STAT- MEDLINE
DCOM- 20070619
LR  - 20131121
IS  - 8755-6863 (Print)
IS  - 1099-0496 (Linking)
VI  - 42
IP  - 4
DP  - 2007 Apr
TI  - Novel tobramycin inhalation powder in cystic fibrosis subjects: pharmacokinetics 
      and safety.
PG  - 307-13
AB  - Aerosolized antibiotics are associated with a high treatment burden that can 
      result in non-adherence to chronic therapy. We evaluated the pharmacokinetics 
      (PK) and safety of tobramycin inhalation powder (TIP), a novel dry-powder 
      formulation designed to deliver a high payload of tobramycin topically to the 
      lungs for management of chronic Pseudomonas aeruginosa infections. This was a 
      multi-center, open-label, sequential-cohort, single-dose, dose-escalation study 
      using the standard 300 mg dose of tobramycin solution for inhalation (TSI) as an 
      active control. Subjects were randomized to TIP or TSI in a 3:1 ratio in each of 
      five cohorts. Measurements included serum and sputum tobramycin concentrations, 
      administration time, serum chemistries, acute change in lung function, and 
      adverse events (AEs). Out of 90 randomized subjects, 86 had data for safety 
      analysis; and 84 had data for PK analysis. Serum tobramycin PK profiles were 
      similar for TIP and TSI. Four capsules of 28 mg TIP (total tobramycin dose 112 
      mg) produced comparable systemic exposure to 300 mg TSI, in less than one-third 
      the administration time. The most common AEs associated with TIP were cough (20%) 
      and dysgeusia (17%). TIP allows for faster and more efficient pulmonary delivery 
      of tobramycin than TSI and has a safety profile that supports continued clinical 
      investigation. The increased rate of local respiratory tract irritation noted 
      with TIP is not unexpected with a high-payload powder formulation. The 
      development of dry powder inhaled antibiotics may represent an important advance 
      in the treatment of chronic lung infections.
CI  - (c) 2007 Wiley-Liss, Inc.
FAU - Geller, David E
AU  - Geller DE
AD  - Nemours Children's Clinic, Orlando, Florida 32806, USA. dgeller@nemours.org
FAU - Konstan, Michael W
AU  - Konstan MW
FAU - Smith, Jeffrey
AU  - Smith J
FAU - Noonberg, Sarah B
AU  - Noonberg SB
FAU - Conrad, Carol
AU  - Conrad C
LA  - eng
GR  - M01-RR00070/RR/NCRR NIH HHS/United States
GR  - M01-RR00080/RR/NCRR NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pediatr Pulmonol
JT  - Pediatric pulmonology
JID - 8510590
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Powders)
RN  - VZ8RRZ51VK (Tobramycin)
SB  - IM
MH  - Administration, Inhalation
MH  - Adolescent
MH  - Adult
MH  - Anti-Bacterial Agents/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Child
MH  - Cough/chemically induced
MH  - Cystic Fibrosis/*complications
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Dysgeusia/chemically induced
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nebulizers and Vaporizers
MH  - Opportunistic Infections/complications/drug therapy
MH  - Powders
MH  - Pseudomonas Infections/complications/*drug therapy
MH  - Pseudomonas aeruginosa
MH  - Sputum/chemistry
MH  - Tobramycin/*administration & dosage/adverse effects/*pharmacokinetics
EDAT- 2007/03/14 09:00
MHDA- 2007/06/20 09:00
CRDT- 2007/03/14 09:00
PHST- 2007/03/14 09:00 [pubmed]
PHST- 2007/06/20 09:00 [medline]
PHST- 2007/03/14 09:00 [entrez]
AID - 10.1002/ppul.20594 [doi]
PST - ppublish
SO  - Pediatr Pulmonol. 2007 Apr;42(4):307-13. doi: 10.1002/ppul.20594.