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In order to identify the optimum particle size and breathing pattern for high peripheral deposition of inhaled drugs in patients with cystic fibrosis, regional deposition in these patients was studied systematically as a function of particle size, inhalation volume and flow rate. Regional deposition was assessed using the single-breath regional deposition technique in which the concentration profile of inhaled and exhaled non-radioactive, monodisperse test particles is analyzed. Using this technique particle deposition within the functional dead space volume and peripherally can be assessed. Regional deposition was measured in 12 patients with cystic fibrosis using 2, 3, 4, and 5.5 µm particles, inhalation volumes of 500, 1000, 1500, and 2000 cm³, and inhalation flow rates of 100, 250, 500, and 750 cm³/sec. Peripheral deposition was highest when 2–3-µm particles were inhaled with air-flow rates of 250–500 cm³/sec. With these parameters peripheral deposition increased with increasing inhalation volume and reached values of about 60% of the total drug inhaled. It has been shown that high peripheral drug deposition can be achieved in patients with CF when inhalations are performed using an optimized combination of particle size and breathing pattern.