Fluticasone propionate plasma concentration and systemic effect: Effect of delivery device and duration of administration

Glenn J. Whelan, Jeffrey L. Blumer, Richard J. Martin, Stanley J. Szefler, Vernon M. Chinchilli, Monica Kraft, Myrna Dolovich, Homer A. Boushey, Reuben M. Cherniack, Timothy J. Craig, Jeffrey M. Drazen, Joanne K. Fagan, John V. Fahy, James E. Fish, Jean G. Ford, Elliott Israel, Susan J. Kunselman, Stephen C. Lazarus, Robert F. Lemanske, Stephen P. PetersChristine A. Sorkness, Tonya Sharp King, Elizabeth Mauger

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Background: Inhaled corticosteroids are the preferred therapy in persistent asthma. Dry powder inhalers (DPIs) generate a larger particle size compared with metered-dose inhalers (MDIs), which affects pulmonary deposition, bioavailability, and subsequent systemic effects of fluticasone propionate (fluticasone). Objective: To examine the relationship of fluticasone pharmacokinetics and cortisol suppression for 2 fluticasone formulations (DPI and MDI) administered in adults over 1-week and 6-week treatment periods. Methods: Two previous studies conducted in adults by the Asthma Clinical Research Network examined relative efficacy and systemic effect of fluticasone from MDI and DPI. Sample sets (n = 33) were analyzed for fluticasone after administration of 352 μg from the MDI, and 400 μg from the DPI formulation, twice daily, after a 1-week treatment period. The second study's sample sets (n = 9) were analyzed for fluticasone after 6 weeks therapy at 352 μg twice daily from the MDI formulation, allowing achievement of steady state. Results: ANOVA revealed a significant trend of increasing fluticasone area under the curve from 0 to time t (AUC0→t) when comparing DPI with MDI for 1 week with MDI for 6 weeks (P < .0001). Similarly, ANOVA revealed increasing cortisol suppression between these groups (P = .007). Linear regression demonstrated that increasing fluticasone AUC0→t was significantly correlated with cortisol suppression (P < .0001; r2 = 0.41). MDI for 6 weeks showed increasing fluticasone AUC (P = .0008, t test) compared with MDI for 1 week, suggesting accumulation. Conclusion: Fluticasone plasma concentrations are significantly greater after MDI compared with DPI, and cortisol suppression is associated with fluticasone plasma concentrations. Accumulation of fluticasone concentrations suggests that time to steady state exceeds 1 week of treatment with MDI.

Original languageEnglish (US)
Pages (from-to)525-530
Number of pages6
JournalJournal of Allergy and Clinical Immunology
Volume116
Issue number3
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

Keywords

  • Cortisol suppression
  • Drug accumulation
  • Dry powder inhaler
  • Fluticasone propionate
  • Metered dose inhaler
  • Pharmacokinetics
  • Steady state

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Whelan, G. J., Blumer, J. L., Martin, R. J., Szefler, S. J., Chinchilli, V. M., Kraft, M., Dolovich, M., Boushey, H. A., Cherniack, R. M., Craig, T. J., Drazen, J. M., Fagan, J. K., Fahy, J. V., Fish, J. E., Ford, J. G., Israel, E., Kunselman, S. J., Lazarus, S. C., Lemanske, R. F., ... Mauger, E. (2005). Fluticasone propionate plasma concentration and systemic effect: Effect of delivery device and duration of administration. Journal of Allergy and Clinical Immunology, 116(3), 525-530. https://doi.org/10.1016/j.jaci.2005.05.044