Pulmonary Distribution and Kinetics of Inhaled

Triamcinolone acetonide (TAA) is an anti-inflammatory steroid used for topical treatment of allergic rhinitis and asthma. Drug deposition onto target tissues is an important parameter, so methods for accurate deposition measurement are needed. Lung deposition is especially problematic to measure because of the large field of view and low relative drug penetration. Our main objective was to use PET to measure the deposition and postdepo-sition kinetics of TAA in the lung after administration from the Azmacort inhaler. The second objective was to evaluate changes in distribution caused by the inhalation spacer that is built into the product. Methods: 11C-labeled TAA was formulated as the Azma-cort product, 5 healthy volunteers inhaled it, and PET scans were obtained of its distribution in the head and chest. Region-of-interest analysis with CT overlay was used to analyze the distribu-tion and kinetics in the airway and lung. Results: From 10 % to 15 % of the inhaled drug dose was deposited in target airway regions in a distally decreasing pattern. Deposition in the oral cavity was about 30 % of the dose. Slow absorption or clearance of drug from target tissues was observed over time. Use of the inhalation spacer caused statistically significant increases in all target tissues (factor of 2–5) and a roughly 40 % decrease in oral deposition. Measurable amounts of the drug remained in target regions throughout the scanning period. Conclusion: Local pulmo-nary distribution and kinetics of inhaled drugs can be measured accurately by PET for drug development. The integrated actuator– spacer significantly enhanced deposition of TAA in target tissues and reduced deposition in the oropharyngeal region. Key Words: PET; inhaler; pulmonary; biodistribution; triamcino-lone acetonide; steroid; drug development; Azmacor