Human receptor kinetics and lung tissue retention of the enhanced-affinity glucocorticoid fluticasone furoate

Respiratory Research

Table 1 Results of the kinetic binding experiments of dexamethasone (Dexa), fluticasone furoate (FF), fluticasone propionate (FP) and mometasone furoate (MF) to the human lung glucocorticoid receptor. Values given represent mean and mean deviation of the mean of three to seven experiments. Binding data of FP and MF are from our previous experiments (Ref. [3]).

Glucocorticoid	k₁ × 10⁵ (L/[mol/min])	k_-1 × 10^-4 [1/min]	K_D [nmol/L]	t_1/2 [h]	RRA
Dexa	10.53 ± 0.35	94.67 ± 5.43	8.80 ± 0.41	1.23 ± 0.04	100 ± 5
FF	37.46 ± 0.73	11.22 ± 0.62	0.30 ± 0.02	10.34 ± 0.59	2989 ± 135
FP	21.17 ± 0.56	10.73 ± 0.65	0.51 ± 0.03	10.82 ± 0.64	1775 ± 130
MF	29.46 ± 1.10	11.82 ± 0.31	0.41 ± 0.03	9.83 ± 0.53	2244 ± 142

Statistically significant differences were observed in the association rate constant k₁ (FF versus FP p ≤ 0.001; FF versus MF p ≤ 0.001; FP versus MF p ≤ 0.001), in equilibrium dissociation rate constant k_D (FF versus FP p ≤ 0.001; FF versus MF p ≤ 0.05; FP versus MF p ≤ 0.05) and in the relative receptor affinity RRA (FF versus FP p ≤ 0.001; FF versus MF p ≤ 0.05; FP versus MF p ≤ 0.01). No statistically significant difference between FF, MF and FP was seen in the dissociation rate constant k_-1 and the derived half life of the receptor complex t_1/2.

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