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.
Bibliographical noteFunding Information:
Received 10 May 2004; accepted 13 July 2004. The authors appreciate the excellent technical assistance of Donna Hartle and Art Galbraith in performing the animal aerosol exposure and surgical removal of tissues. This work was completed with partial financial support of NIH P01-CA96964. Address correspondence to Timothy Scott Wiedmann, PhD, University of Minnesota, Department of Pharmaceutics, 308 Harvard St. SE, Minneapolis, MN 55455, USA. E-mail: email@example.com
- Lung cancer