Analysis of Fenoterol and Ipratropium Transfer from Human Lung Tissue into Human Plasma Using a Dynamic Dialysis Model

Abstract

Aims: The aim of the current study was to establish a simple and yet as much as possible physiologic approach for a simulation of the pulmonary absorption process to compare different inhaled drugs or drug formulations. Methodology: We designed a dialysis setting that allowed monitoring the drug release from human lung tissue into a continuous-flow plasma compartment. For proof-of-concept experiments we chose the glucocorticoid fluticasone propionate (FP) as model compound. For subsequent experiments we selected a commercially available metered dose inhaler delivering a fixed combination of the short-acting ß2-agonist fenoterol and the muscarinic antagonist ipratropium bromide. Results: With the novel dynamic dialysis model we observed high drug transport rates from the lung tissue into plasma including an elimination phase. The concentration profile in the plasma compartment of our model system was similar to the plasma concentration courses after inhalation of FP. Compared to FP significantly higher drug fractions of fenoterol and ipratropium bromide were released into plasma and the transfer of ipratropium was more pronounced compared to fenoterol. Again, concentration profiles in plasma were alike to those described in clinical studies. Conclusion: We suggest that this model is appropriate for rapid assessment of comparative diffusion behaviour of drugs or drug formulations from lung tissue into plasma.