PULMONARY DELIVERY OF BECLOMETHASONE LIPOSOME AEROSOL IN VOLUNTEERS -TOLERANCE AND SAFETY

Study objective: To test the tolerance and safety of single doses of b eclomethasone dipropionate (Bec)-dilauroylphosphatidylcholine (DLPC) l iposome aerosol in volunteers. Design: Single-dose inhalations of Lipo some preparations of Bec-DLPC and DLPC alone were administered for 15 min from a jet nebulizer (Puritan-Bennett, modified twin jet; mass med ian aerodynamic diameter of 1.6 mu m) under close clinical and laborat ory surveillance. Two dose levels (0.5 mg Bec/12.5 mg DLPC per millili ter, and 1.0 mg Fee and 25 mg DLPC per milliliter in the reservoirs, r espectively) were administered. The Fee doses were selected to approxi mate the dosages of this glucocorticoid used with metered-dose inhaler s (MDIs). First, four volunteers were exposed to an initial low dose; the mean (+/- SD) inhaled doses were 0.56 +/- 0.07 mg of see and/or 14 .0 +/- 1.8 mg of DLPC. Subsequently, a second group of sis volunteers was exposed to a higher dose; the mean (+/- SD) inhaled doses were 1.2 9 +/- 0.14 mg of Bec and/or 34.6 +/- 6.8 mg of DLPC. Setting: Outpatie nt and inpatient. Patients: Normal male (n=6) and female (n=4) adult v olunteers. Interventions: Inhalation of Bec-DLPC and DLPC liposome aer osols in a single-dose tolerance study involving 10 normal volunteers. Measurements and results: Spirometry, clinical observations, clinical chemistry, and hematology were monitor-ed. No adverse clinical or lab oratory events were observed. Conclusions: Bec-DLPC liposome aqueous a erosol was well tolerated in doses equivalent to these currently admin istered by MDIs and dry powder inhalers for treatment of asthma.