PHARMACOKINETICS AND SYSTEMIC EFFECTS OF INHALED FLUTICASONE PROPIONATE IN HEALTHY-SUBJECTS

Aims The present study was undertaken to see whether the difference in plasma cortisol suppression between single and repeated dosing of flu ticasone propionate (FP) can be explained by systemic accumulation. Me thods Twelve healthy subjects (six women) were given, in a crossover f ashion, a single dose inhalation (1000 mu g) of FP via Diskhaler(R) an d repeated inhalations (1000 mu g twice daily) every 12 h during 7 day s. There was a washout period of 2 weeks between the treatments. An in travenous dose of 20 mu g FP was given as a reference. Plasma concentr ations of FP for each treatment were determined by liquid chromatograp hy plus tandem mass spectrometry. Plasma cortisol after the inhaled do ses was determined using an immunoassay and was compared with baseline values. Results The average plasma concentration of FP was about 1.7 times higher after multiple inhalations than after a single dose. Syst emic availability, mainly attributable to pulmonary deposition, was 15 .6 [13.6-18.0]% of the nominal dose. Daytime plasma cortisol suppressi on vs baseline was 47 [20-65]% and 95 [93-97]% for the single and repe ated doses, respectively. Conclusions To conclude, a slow elimination of FP leads to accumulation during repeated dosing. This accumulation may explain the marked decrease in plasma cortisol seen during treatme nt with fluticasone propionate within the clinical dose range.