Receptor-ligand interactions of fluticasone propionate (FP), a glucoco
rticoid used for inhalation therapy,, were determined and compared wit
h dexamethasone, budesonide, and beclomethasone-17-monopropionate, the
active metabolite of beclomethasone dipropionate. Two approaches, eva
luation of binding kinetics and competition assays, were applied to ob
tain relative receptor affinities (RRAs) with dexamethasone as referen
ce. A higher association I ate constant and a distinctly lower dissoci
ation rate constant for FP compared with the other glucocorticoids res
ulted in an equilibrium dissociation constant (K-d) of 0.49 nmol/l. K-
d dexamethasone was 9.36 nmol/l; derived RRA of FP was 1910. The calcu
lated half-time of the FP-receptor complex was 10 h, thus exceeding th
e half-times of all other glucocorticoids as well as their RRAs. Compe
tition assays clearly confirmed the rank order of the tested glucocort
icoids, although RRAs were generally lower than those found in kinetic
assays and strongly dependent on the assay conditions. The high recep
tor affinity of FP is reflected by clinical trials demonstrating its s
uperiority to other glucocorticoids. For therapeutic application, the
long half-time of the FP-receptor complex should support the practical
ity of longer dose-intervals.