Plasma concentrations of fluticasone propionate and budesonide following inhalation: effect of induced bronchoconstriction.

Author(s): Mortimer KJ, Tattersfield AE, Tang Y, Wu K, Lewis S, Hochhaus G, Harrison TW

Affiliation(s): Division of Respiratory Medicine, University of Nottingham, UK. kevinmortimer@msn.com

Publication date & source: 2007-10, Br J Clin Pharmacol., 64(4):439-44. Epub 2007 Aug 15.

Publication type: Randomized Controlled Trial

AIMS: To determine whether and to what extent bronchoconstriction affects plasma concentrations of fluticasone and budesonide following inhalation. METHODS: Twenty people with mild asthma inhaled 1000 microg fluticasone (Accuhaler) plus 800 microg budesonide (Turbohaler) on two visits. On one occasion, prior to drug inhalation, FEV(1) was decreased by at least 25% using inhaled methacholine. Plasma drug concentrations were measured for each drug over 5 h and area under the plasma concentration-time curve (AUC(0,5 h)) compared between visits. RESULTS: The mean difference in FEV(1) prior to drug inhalation on the 2 days was 33%. AUC(0,5 h) values for fluticasone and budesonide were lower by a median of 60% (IQR 36-75) and 29% (IQR 2-44), respectively, when administered following bronchoconstriction; the reduction was greater for fluticasone than for budesonide, P = 0.007. CONCLUSIONS: The lower plasma concentrations of fluticasone and, to a lesser extent, budesonide seen when the drugs were inhaled following induced bronchoconstriction, is likely to reflect variations that will occur with fluctuations in airway caliber in asthma.