Lung Deposition of Fenoterol and Flunisolide Delivered Using a Novel Device for Inhaled Medicines: Materials and Methods

The aims of the two randomized three-way crossover studies in healthy volunteers reported in this article were to examine, using gamma scintigraphy, the in vivo lung deposition of (1) the bronchodilator fenoterol and (2) the corticosteroid flunisolide following single-dose inhalation. Comparisons were made of the total and regional deposition of these drugs delivered by the new device, conventional MDIs, and MDIs with spacer devices. Furthermore, in the flunisolide study, the effect on lung deposition of a modification of the RESPIMAT by the addition of a baffle in the mouthpiece, designed to eliminate large, “nonrespirable” droplets from the spray, was investigated.
Materials and Methods
Subjects
In each of the two studies, 12 healthy male or nonpregnant female, nonsmoking volunteers aged between 18 and 65 years completed the study (Table 1). All subjects had normal lung function as determined by measurements of FEV1? FVC, and peak expiratory flow rate that were >80% of the predicted value. Each volunteer underwent a medical examination to confirm that they were healthy before entering the study (within 21 days of the first study day) and within 14 days of completing the study. This included a physical examination, hematology, clinical chemistry, urinalysis, and an ECG. Both studies were approved by the Quorn Research Review Committee, Leicestershire, UK, and permission for the administration of the radionuclide “mTc and the radioactive inert gas 81mKr was obtained from the Department of Health, London, UK. Each volunteer gave written informed consent prior to participating in the study. canadian neighbor pharmacy

Study Design
Both studies were open, randomized, and of a three-way crossover design. The volunteers were each studied on three separate occasions at least 44 h apart. Radiolabeled drug from one of three inhaler devices was inhaled in a randomized order. In the fenoterol study, subjects received a single dose of fenoterol hydrobromide by (1) the RESPIMAT device (Boehringer In-gelheim), (2) MDI, and (3) MDI with Aerochamber 150-mL spacer device (Trudell Medical; London, Ontario Canada). In the flunisolide study, subjects inhaled a single dose of flunisolide by (1) the RESPIMAT device, (2) a modified version of the RESPIMAT with a baffle in the mouthpiece, and (3) MDI with Inhacort spacer device (Boehringer Ingelheim; Ingelheim, Germany). The metered doses of fenoterol and flunisolide were 100 μg and 250 μg, respectively. In the RESPIMAT, fenoterol and flunisolide were delivered as aqueous and 96% ethanol formulations, respectively.
Table 1—Demographics of Study Volunteers

Fenoterol Study Flunisolide Study
No. of subjects 12 12
Male/female 5/7 6/6
Age, yr 27.4 (20-39) 27.3 (20-44)
Height, cm 169.8 (151-188) 168.5 (157-188)
Weight, kg 70.3 (47-98) 69.8 (52-87)f
FEVl5 % predicted 106 (92-125) 97 (83-114)

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