A pharmacokinetics and safety comparison of a highly concentrated tobramycin solution with TOBI

J Aerosol Med Pulm Drug Deliv. 2014 Jun;27(3):185-92. doi: 10.1089/jamp.2012.1022. Epub 2013 Jun 22.

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.

Conclusion: Inhaled therapy with T100 PARI delivered by an investigational eFlow offers a patient treatment time benefit and comparable safety and pharmacokinetics.

Keywords: T100 PARI; TOBI; eFlow; pharmacokinetics; safety; tobramycin.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adult
  • Aerosols
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacokinetics*
  • Area Under Curve
  • Chemistry, Pharmaceutical
  • Child
  • Cystic Fibrosis / diagnosis
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / physiopathology
  • Drug Monitoring
  • Equipment Design
  • Forced Expiratory Volume
  • Germany
  • Humans
  • Lung / metabolism*
  • Lung / physiopathology
  • Male
  • Nebulizers and Vaporizers
  • Sputum / metabolism
  • Tobramycin / administration & dosage*
  • Tobramycin / adverse effects
  • Tobramycin / blood
  • Tobramycin / chemistry
  • Tobramycin / pharmacokinetics*
  • Treatment Outcome
  • Young Adult

Substances

  • Aerosols
  • Anti-Bacterial Agents
  • Tobramycin