Pharmacoscintigraphic and pharmacokinetic evaluation of tobramycin DPI formulations in cystic fibrosis patients.

Tobramycin dry powder formulations were evaluated by gamma scintigraphy and pharmacokinetic methods. In an open single-dose, three-treatment, three-period, cross-over study, nine cystic fibrosis patients received both the two test products and the reference product Tobi (nebulizer solution) in order to assess lung deposition and systemic comparative bioavailability of the two investigational inhaled products versus the marketed inhaled comparator product. The percentage of dose (mean+/-SD) in the whole lung was 53.0+/-10.0% for the tobramycin Form 1, 34.1+/-12.4% for the tobramycin Form 2 and 7.6+/-2.7% for the comparator product Tobi. Lung deposition expressed as a percentage of the nominal dose was thus estimated to be 7.0 and 4.5 times higher for the Tobra Form 1 and Tobra Form 2 than for the Tobi, respectively. Furthermore, the systemic bioavailability (adjusted to correspond to the same drug dose as that of the comparator product deposited in the lung) was found to be 1.6 times higher for the comparator product Tobi than for the two DPI formulations. The principal advantages of the DPI formulations include reduced systemic availability and thus, side effects, and higher dose levels of the drug at the site of drug action.