Pharmacokinetics and systemic activity of fluticasone via Diskus (R) and pMDI, and of budesonide via Turbuhaler (R)

Aims To determine the basal pharmacokinetics, lung uptake and plasma cortis ol suppression for two commonly prescribed inhaled corticosteroids. Methods Twenty-one subjects (13 healthy and 8 mild asthmatic patients) rece ived fluticasone propionate via a chlorofluorocarbon-propelled pressurized metered-dose inhaler (pMDI) (healthy subjects only) and Diskus(R) and budes onide via Turbuhaler(R), 1000 mug twice daily for 7 days. Intravenous doses (200 mug) of both compounds were used as references. Plasma concentrations of fluticasone and budesonide were determined during 48 h by liquid chroma tography plus tandem mass spectrometry (LC-MS-MS). Plasma concentrations of cortisol were determined by LC-MS every second hour for 24 h at baseline, and following each treatment. Results The volume of distribution was found to be larger and the eliminati on half-life and mean absorption time longer for fluticasone than for budes onide. The systemic availability of budesonide via Turbuhaler (39%) was sig nificantly higher than that of fluticasone via Diskus (13%) (ratio 3.0 [2.5 , 3.6] with 95% confidence interval [CI]), and via pMDI (21%) (ratio 1.8 [1 .3, 2.31). In addition, at steady state the systemic availability of flutic asone via pMDI was significantly higher than via Diskus (ratio 1.6 1.1, 2.2 ]). The lung deposition of budesonide via Turbuhaler was 2.2-fold [1.7, 2.9 ] higher than that of fluticasone pMDI and 3.4-fold [2.8, 4.0] higher than that of fluticasone Diskus. In addition, the lung deposition of fluticasone via pMDI was 1.5-fold [ 1.1, 2.9] higher than that via the Diskus inhaler. Plasma cortisol (24 h) was significantly reduced vs baseline for all three treatments. The cortisol concentration vs baseline was 12% for fluticasone pMDI, which was significantly lower (ratio 0.32 [0.24, 0.42]) than that fo r fluticasone Diskus (39%), and for budesonide Turbuhaler (46%) (ratio 0.27 [0.21, 0.37]). The plasma cortisol concentration did not differ significan tly between treatments with fluticasone Diskus and budesonide Turbuhaler (r atio 0.87 [0.65; 1.15]). Conclusions Budesonide and fluticasone differ in their pharmacokinetic prop erties in that although clearance is the same, the rate of uptake and elimi nation is slower for fluticasone. Despite a significantly higher pulmonary availability of budesonide via Turbuhaler, the plasma cortisol suppression is less than that of fluticasone via pMD1 and similar to that of fluticason e via Diskus. There is no indication of any difference between healthy subj ects and mild asthmatic patients in the pharmacokinetics and plasma cortiso l suppression of fluticasone and budesonide.