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Pitfalls in Understanding Local Exposure

Bäckman P, Olsson B.

Respiratory Drug Delivery 2016. Volume 1, 2016: 125-132.

Abstract:

We have applied a mechanistic computer based model to investigate the impact of deposition, release rate, and solubility on local and systemic exposure. The observed plasma concentration of fluticasone propionate and budesonide following inhalation by healthy subjects and asthmatics in a clinical study were successfully simulated by the model. The plasma concentration-time profiles for budesonide did not differ between healthy subjects and asthmatics, whereas the simulated tissue concentration in the large bronchi showed a much longer duration for asthmatics than for healthy subjects. This indicated that equivalence of systemic exposure may not necessarily imply equivalence of local exposure. We further used the model to investigate extent and rate of absorption from different lung regions as a function of solubility and particle size. Results indicated that a low solubility compound may exhibit permeation-limited absorption in central airways and dissolution-limited absorption in peripheral airways.