Pharmacokinetic/pharmacodynamic evaluation of urinary cortisol suppression after inhalation of fluticasone propionate and mometasone furoate

摘要

What is already known about this subject class="unordered" style="list-style-type:disc">Mometasone furoate (MF) is a new inhaled glucocorticoid for which the first reports suggested a low degree of systemic side-effects and low systemic availability.Recent studies of Fardon and colleagues have shown that MF's cortisol suppression is similar to that of fluticasone.Pharmacokinetic/dynamic evaluations of MF's systemic side-effects, probing whether systemic side-effects can be explained by systemic availability, plasma protein binding and receptor binding affinity, are lacking in the literature.What this study adds class="unordered" style="list-style-type:disc">This study shows that the systemic availability of MF and fluticasone propionate (FP) are similar and that systemic availability is directly related to the dose.It also shows that the metabolites of MF are present only in very low concentrations at most, contrary to results in rats.The observed cortisol suppression of FP and MF is related to the trough plasma concentrations and seems to be in agreement with its observed systemic availability, plasma protein binding and receptor binding affinity.AimFluticasone propionate (FP) and mometasone furoate (MF) are inhaled corticosteroids that possess a high ratio of topical to systemic activity. The systemic bioavailability of MF has been claimed to be minimal (1%). FP has been shown to exhibit the same degree of systemic effects, but its systemic availability is between 13 and 17%. We hypothesize that FP and MF have comparable systemic availabilities that can explain their potential to cause systemic effects.