Inhalation of tobramycin in patients with cystic fibrosis: comparison of two methods

• Published in: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2007-11, Vol.58 Suppl 5 (Pt 1), p.141-154
• Main Authors: Dopfer, R, Brand, P, Müllinger, B, Hunger, T, Häussermann, S, Meyer, T, Scheuch, G, Siekmeier, R
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adolescent; Adult; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacokinetics; Cross-Over Studies; Cystic Fibrosis - drug therapy; Cystic Fibrosis - physiopathology; Drug Administration Schedule; Equipment Design; Feasibility Studies; Forced Expiratory Volume; Humans; Nebulizers and Vaporizers; Respiratory Mechanics; Tobramycin - administration & dosage; Tobramycin - blood; Tobramycin - pharmacokinetics; Treatment Outcome
• ISSN: 0867-5910

Inhalant tobramycin is established in the treatment of cystic fibrosis patients. Conventional nebulizers require a large amount of the expensive compound, because only a small fraction is deposited in the targeted lung region. In contrast, techniques based on controlled inhalation allow a high and reproducible deposition of the drug in specific lung regions. In our study we compared the efficiency of two techniques based on conventional and controlled inhalation in 16 cystic fibrosis patients aged 13-39 years. Inhalations with the doses of tobramycin of 300 mg and 150 mg were performed twice daily for three days. The efficiency of the drug deposition was measured by the determination of its serum concentration 1 h after the end of the inhalation. The mean FEV1 value in our patients was 61% of predicted, range 36%-116%. There were no differences in tobramycin serum concentrations among the three study days in both methods (controlled inhalation: 0.983 +/-0.381(+/-SD) mg/l, 1.119+/-0.448 mg/l, 1.194+/-0.568 mg/l; conventional inhalation: 1.075+/-0.798 mg/l, 1.294 0.839 mg/l and 1.269+/-0.767 mg/l, on Day 1, Day 2, and Day 3, respectively). Even though the drug amount was double in the conventional technique, there was no significant difference in its overall serum concentration from the three study days (conventional inhalation: 1.210+/-0.783 mg/l, controlled inhalation: 1.092+/-0.461 mg/l). In addition, the coefficient of variation and the required inhalation time were shorter in controlled inhalation than in conventional inhalation (42% vs. 65% and 7-8 min vs. 20 min, respectively). Our data suggest that controlled inhalation can significantly reduce the amount of a drug required for therapy, the inhalation time required for drug deposition, and the variability of pulmonary dosage. It seems probable that controlled inhalation can improve the antibiotic prevention of pulmonary infection.