Fluticasone propionate plasma concentration and systemic effect: effect of delivery device and duration of administration.
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 microg from the MDI, and 400 microg 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 microg 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 (AUC(0-->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 AUC(0-->t) was significantly correlated with cortisol suppression (P<.0001; r(2)=0.41). MDI for 6 weeks showed increasing fluticasone AUC (P=.0008, t test) compared with MDI for 1 week, suggesting accumulation.


CONCLUSIONS
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.
Whelan
Glenn J
GJ
Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA. WhelanG@njc.org
Blumer
Jeffrey L
JL
Martin
Richard J
RJ
Szefler
Stanley J
SJ
D000280:Administration, Inhalation; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D002986:Clinical Trials as Topic; D000068298:Fluticasone; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D036501:Metered Dose Inhalers; D011208:Powders; D013997:Time Factors
D000730:Androstadienes; D001993:Bronchodilator Agents; D011208:Powders; D000068298:Fluticasone; D006854:Hydrocortisone