Plasma concentrations of fluticasone propionate and budesonide following inhalation: effect of induced bronchoconstriction.
OBJECTIVE
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.
Mortimer
Kevin J
KJ
Division of Respiratory Medicine, University of Nottingham, UK. kevinmortimer@msn.com
Tattersfield
Anne E
AE
Tang
Yufei
Y
Wu
Kai
K
Lewis
Sarah
S
Hochhaus
Gunther
G
Harrison
Tim W
TW
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage* / Q000097:blood* / Q000494:pharmacology; D001249:Asthma / Q000097:blood / Q000188:drug therapy*; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019819:Budesonide / Q000008:administration & dosage* / Q000097:blood* / Q000494:pharmacology; D018592:Cross-Over Studies; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000730:Androstadienes; D001993:Bronchodilator Agents; D019819:Budesonide; D000068298:Fluticasone
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