Objectives: To compare the systemic bioavailability
(assessed by cortisol suppression) of high-dose budesonide when given
by four inhaler devices and orally. Also studied are the relative
systemic potencies of three inhaled steroids (budesonide, fluticasone
propionate, and beclomethasone dipropionate) when given by metered-dose
inhaler (MDI) with a large volume spacer.
Double-blind, crossover, placebo-controlled trial.
Participants: Sixteen healthy, steroid-naive adult
Methods: On separate occasions, each
subjects took 4 mg of budesonide through the following devices: MDI
alone, MDI with 750-mL spacer, dry-powder inhaler and nebulizer; 4 mg
of budesonide was also taken orally to assess the effects of GI
absorption. For the drug comparison, each subject took 4 mg of
budesonide, fluticasone, and beclomethasone, and 2 mg of budesonide and
fluticasone by MDI and spacer.
percent suppression (95% confidence interval) of 9:00 am
cortisol with budesonide was observed with MDI alone (73% [57 to
90]) and turbohaler (72% [58 to 86]) compared with MDI spacer (42%[
22 to 64]) and oral administration (14% [+6- to −34]). Nebulized
budesonide produced an insignificant rise in 9:00 am
cortisol level. The most suppressive drug (given by MDI spacer) was
fluticasone at 4 mg (86% [82 to 91]) and at 2 mg (72% [59 to
85]). The least suppressive drug was budesonide at 4 mg (43% [22 to
64]) and at 2 mg (25% [3 to 47]). The effects of 4 mg of
beclomethasone were intermediate (66% [49 to 82%]).
Conclusions: The choice of delivery device for
administration of budesonide can lead to important differences in
systemic bioavailability. Fluticasone has greater systemic potency than
budesonide or beclomethasone when given at microgram equivalent dosage.
The systemic potency ratio of fluticasone propionate to budesonide in
normal human volunteers in the present study is similar to the
therapeutic potency ratio of the drug in asthmatic patients
HPA = hypothalamic-pituitary-adrenal; MDI = metered-dose inhaler