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Is Systemic PK Really an Indicator of Pulmonary Deposition? A Fluticasone Propionate Case Study

Kuehl PJ, Barrett EG, Burke M, Chand R, DuBose D, Moeller B, Rudolph K, Sheeler R, Vodak D.

Respiratory Drug Delivery 2016. Volume 1, 2016: 55-62.

Abstract:

Systemic pharmacokinetics (PK) is used as a measurement for pulmonary dose following oral inhalation. The ability of systemic PK to accurately reflect pulmonary dose and the correlation to local efficacy is difficult to assess in a clinical setting. Therefore, this non-clinical study was designed to evaluate the hypothesis that systemic PK is not always an appropriate measurement for pulmonary dose. Secondarily, the local pharmacodynamics (PD) were quantified to assess the correlation between systemic PK on local efficacy. The study designed used fluticasone propionate (FP) as a model compound within a canine PK and PD study. Dose matched aerosols of fluticasone were delivered from Flovent^® pMDI, crystalline dry powder, and amorphous dry powder. Systemic PK and local efficacy (inflammation) were determined following each formulation. The systemic PK indicated a marked difference between Flovent pMDI and the dry powder formulations. The PD assessment indicated that all three formulations resulted in a decrease in total cell number within the bronchoalveolar lavage fluid. These data indicate that systemic PK may not always accurately predict pulmonary dose and correlate to local efficacy.