LUNG DISTRIBUTION OF THE CHEMOPREVENTIVE AGENT DIFLUOROMETHYLORNITHINE (DFMO) FOLLOWING ORAL AND INHALATION DELIVERY

The inhalation delivery of difluoromethylornithine (DFMO) was evaluated to determine its feasibility for use in lung cancer chemoprevention. Aerosol droplets of DFMO were produced, and the solvent was removed by a reflux drying column. Equivalent doses of DFMO (40 mg/kg) were given over 10 minutes by inhalation and by gavage, and the serum and tissue levels were determined. Inhalation of DFMO resulted in a peak lung concentration 80 times higher and area under the curve (AUC) that was 35 times higher than oral dosing. The estimated pharmacokinetic advantage based on serum and lung AUCs was 13 in favor of inhalation.