TOLERANCE OF VOLUNTEERS TO CYCLOSPORINE-A DILAUROYLPHOSPHATIDYLCHOLINE LIPOSOME AEROSOL

Cyclosporine A (CsA) in liposomes of dilauroylphosphatidylcholine (DLP C), containing 118 mu g of CsA/L of aerosol with a particle size of 1. 6 to 1.7 mu m diameter, was inhaled by 10 nonsmoking, normal volunteer s each for 45 min. Aerosol was administered through an Aerotech II neb ulizer (CIS-US, Inc., Bedford, MA) mouthpiece. Eight of the 10 volunte ers had tracheal irritation and intermittent coughing following exposu re. FEV1 and FVC values were mildly reduced, but returned to normal in 1 h. Blood chemical and hematologic values were unchanged at any time point after as opposed to before inhalation. Nine of the 10 volunteer s later inhaled DLPC only, administered through the nebulizer mouthpie ce, There was no change in FEV1 or FVC values, and there was no coughi ng or tracheal irritation. Subsequently, five of the volunteers who ha d previously had respiratory reactions inhaled CsA-DLPC liposome aeros ol for 45-min, but through a mouth-only face mask. There was no trache al irritation, coughing, or changes in spirometric measures. Blood con centrations of CsA at 15 min after the 45-min inhalation with a face m ask averaged 83 +/- 42 ng/ml (mean +/- SD). At 24 h after treatment, C sA was undetectable in blood of the initial 10 volunteers. These studi es indicate that CsA-DLPC liposome aerosol can be safely explored as a treatment for patients with moderately severe asthma.