Pulmonary distribution and kinetics of inhaled [C-11]triamcinolone acetonide

Triamcinolone acetonide (TAA) is an anti-inflammatory steroid used for topi cal treatment of allergic rhinitis and asthma. Drug deposition onto target tissues is an important parameter, so methods for accurate deposition measu rement are needed. Lung deposition is especially problematic to measure bec ause of the large field of view and low relative drug penetration. Our main objective was to use PET to measure the deposition and postdeposition kine tics of TAA in the lung after administration from the Azmacort inhaler. The second objective was to evaluate changes in distribution caused by the inh alation spacer that is built into the product. Methods: C-11-labeled TAA wa s formulated as the Azmacort product, 5 healthy volunteers inhaled it, and PET scans were obtained of its distribution in the head and chest. Region-o f-interest analysis with CT overlay was used to analyze the distribution an d 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 p attern. Deposition in the oral cavity was about 30% of the dose. Slow absor ption 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 depositio n. Measurable amounts of the drug remained in target regions throughout the scanning period. Conclusion: Local pulmonary distribution and kinetics of inhaled drugs can be measured accurately by PET for drug development. The i ntegrated actuator-spacer significantly enhanced deposition of TAA in targe t tissues and reduced deposition in the oropharyngeal region.