Clinical pharmacology study of Bramitob, a tobramycin solution for nebulization, in comparison with Tobi

Paediatr Drugs. 2007;9 Suppl 1:3-9. doi: 10.2165/00148581-200709001-00002.

Abstract

Background and objectives: To compare in vitro characteristics and pharmacokinetics of Bramitob, a preservative-free tobramycin solution for nebulization, and Tobi in patients with cystic fibrosis (CF) and Pseudomonas aeruginosa infection.

Methods: In vitro characteristics of Bramitob and Tobi were evaluated using Pari TurboBoy/LC Plus and the Systam 290 LS nebulizers. In the randomized, double-blind, two-way crossover pharmacokinetic study, 11 patients with CF received a single nebulized dose (300mg) of Bramitob or Tobi, separated by a 7-day washout period. Plasma and sputum tobramycin concentrations were measured immediately before and over 24 hours after administration.

Results: Bramitob and Tobi performed alike during nebulization. The fine particle fraction was 33-37% and the mass median aerodynamic diameter was <5microm. Nine patients completed the pharmacokinetic study. Tobramycin plasma profiles after administration of Bramitob or Tobi were similar, with a peak at 90 and 72 minutes after inhalation of Bramitob and Tobi, respectively. The elimination half-life was ~5 hours for both products. The relative bioavailability of Bramitob to Tobi was 1.01, indicating comparable systemic exposure. Peak sputum concentration of tobramycin was 816 +/- 681 microg/g for Tobi and 1289 +/- 851 microg/g for Bramitob and was >400 microg/g (threshold sufficient for an antibacterial effect against P. aeruginosa) in 5 out of 9 patients receiving Tobi and 8 out of 9 patients receiving Bramitob. All adverse events were considered mild and judged not related to the study drugs.

Conclusions: In vitro performance of Bramitob((R)) was similar when nebulized with Pari TurboBoy k/LC Plus and Systam 290 LS nebulizers and comparable to that of TobiThe systemic bioavailability of tobramycin was similar after administration of either Bramitob or Tobi; however, in sputum samples the tobramycin peak concentration was slightly greater after administration of Bramitob than after Tobi.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacokinetics*
  • Biological Availability
  • Chronic Disease
  • Cross-Over Studies
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Nebulizers and Vaporizers
  • Particle Size
  • Pseudomonas Infections / complications
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas aeruginosa
  • Therapeutic Equivalency
  • Tobramycin / administration & dosage
  • Tobramycin / adverse effects
  • Tobramycin / pharmacokinetics*

Substances

  • Anti-Bacterial Agents
  • Tobramycin