title: A pharmacokinetics and safety comparison of a highly concentrated tobramycin solution with TOBI.
abstract: BACKGROUND
  Improved inhalation device/drug combinations are necessary to advance inhaled antibiotic therapy in cystic fibrosis (CF). Previously, for a novel drug/inhaler combination, equivalent lung deposition was demonstrated; here, we investigated its safety and pharmacokinetics.
  
  
  METHODS
  In a randomized, open-labeled, multicenter, active controlled, parallel 28-day study, we compared a new tobramycin formulation (T100 PARI, 150 mg/1.5 mL) nebulized with a drug-specific PARI eFlow(®) nebulizer and TOBI(®) (300 mg/5 mL) nebulized with a PARI LC PLUS(®) nebulizer in 78 CF patients.
  
  
  RESULTS
  Noninferiority of the primary endpoint peak plasma tobramycin concentrations and the secondary endpoint area under the concentration time curves in plasma were observed. Sputum concentrations exceeded expected minimum inhibitory concentrations of Pseudomonas aeruginosa and were the same across both treatment groups, as were tolerability and safety. The nebulization time (4.6 vs. 16.1 min) was much shorter for the new drug/device combination.
  
  
  CONCLUSIONS
  Inhaled therapy with T100 PARI delivered by an investigational eFlow offers a patient treatment time benefit and comparable safety and pharmacokinetics.
authors.affiliation: 1 Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital der Ludwig-Maximilians-Universität München , 80337 München, Germany .
authors.forename: Matthias
authors.initials: M
authors.lastname: Griese
authors.forename: Claudia
authors.initials: C
authors.lastname: Eismann
authors.forename: Gerhard
authors.initials: G
authors.lastname: Börner
authors.forename: Oliver
authors.initials: O
authors.lastname: Denk
authors.forename: Jörg Michael
authors.initials: JM
authors.lastname: Schierholz
authors.forename: Manfred
authors.initials: M
authors.lastname: Keller
authors.forename: H
authors.initials: H
authors.lastname: Mazurek
authors.forename: Matthias
authors.initials: M
authors.lastname: Kappler
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000336:Aerosols; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D002648:Child; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D016903:Drug Monitoring; D004867:Equipment Design; D005541:Forced Expiratory Volume; D005858:Germany; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009330:Nebulizers and Vaporizers; D013183:Sputum / Q000378:metabolism; D014031:Tobramycin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000336:Aerosols; D000900:Anti-Bacterial Agents; D014031:Tobramycin
keywords: T100 PARI; TOBI; eFlow; pharmacokinetics; safety; tobramycin