title: Clinical pharmacology study of Bramitob, a tobramycin solution for nebulization, in comparison with Tobi.
abstract: OBJECTIVE
  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.
authors.affiliation: R & D Chiesi Farmaceutici S.p.A., Parma, Italy. g.poli@chiesigroup.com
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Poli
authors.forename: Daniela
authors.initials: D
authors.lastname: Acerbi
authors.forename: Roberto
authors.initials: R
authors.lastname: Pennini
authors.forename: Annamaria
authors.initials: A
authors.lastname: Soliani Raschini
authors.forename: Mario Ermanno
authors.initials: ME
authors.lastname: Corrado
authors.forename: Hans Georg
authors.initials: HG
authors.lastname: Eichler
authors.forename: Irmgard
authors.initials: I
authors.lastname: Eichler
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D002908:Chronic Disease; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa; D013810:Therapeutic Equivalency; D014031:Tobramycin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D014031:Tobramycin