Nasal retention of budesonide and fluticasone in man: Formation of airway mucosal budesonide-esters in vivo

Aims The efficacy of topical glucocorticosteroids in rhinitis and asthma is likely to depend on drug retention in the airway mucosa. With fluticasone propionate, retention may be achieved exclusively by lipophilicity, whereas for budesonide an additional possibility may be provided by its ability to form fatty acid esters in the air-way mucosa that release the active drug. The aim of the present study was to determine the nasal mucosal retention of budesonide and fluticasone propionate, and the occurrence of budesonide- esters (budesonide-oleate, budesonide-palmitate) in the nasal mucosa. Methods In the present study, involving 24 healthy subjects, we have examin ed nasal mucosal drug retention of single doses of topical budesonide (256 mug) and fluticasone propionate (200 mug) Treatments were given consecutive ly and the administration sequence was randomised. Subjects were randomised into four parallel groups and two nasal biopsies were taken from each subj ect, i.e. before and at 2 h, at 2 and 6 h, at 6 and 24 h, or before and at 24 h after drug administration, resulting in 12 biopsies/time point. The me asurement of unesterified budesonide, budesonide-oleate, budesonide-palmita te, and fluticasone propionate was based on microwave extraction procedures combined with liquid-chromatography/tandem mass-spectrometry. Results Neither of the analytes was detected in samples taken before glucoc orticosteroid administration. After administration, unesterified budesonide , budesonide-esters, and fluticasone propionate were detected in the tissue from 23, 20, and 19 subjects, respectively. The mean tissue levels of bude sonide at 2 and 6 h were 1051 and 176 pmol g(-1); the mean levels of flutic asone propionate at these time points were 237 and 10 pmol g(-1). The dose- corrected budesonide/fluticasone propionate tissue concentration ratios wer e 3.5 (P=0.07) and 13.7 (P<0.0002), respectively. At 24 h, budesonide and f luticasone propionate were detected in 8/12 and 3/12 of the biopsies, respe ctively. Conclusions The present study demonstrates the formation of budesonide-este rs in the human nasal mucosa in vivo, and that budesonide is retained in th e nasal mucosa to a greater extent than fluticasone propionate. It is sugge sted that the formation of budesonide-esters and their subsequent release o f budesonide contributes to an extended retention of budesonide in the airw ay mucosa.