BACKGROUND: Spacer devices facilitate respirable drug delivery. A novel breath-actuated antistatic spacer with integrated vortex chamber (Synchro-Breathe) device has been developed, which is compact,portable and user friendly as compared to conventional spacers which are bulky and cumbersome. The relative bioavailability to the lung of inhaled fluticasone and salmeterol combination is primarily dependent on respirable dose delivery and can be reliably quantified using adrenal suppression and early fall in serum potassium (marker of systemic beta-2 adrenoreceptor response) as surrogate markers for delivered lung dose. AIMS AND OBJECTIVES: To compare the in vivo relative bioavailability to the lung of Hydrofluoroalkane(HFA) Seretide delivered via Synchro-Breathe (SB); an optimally prepared 750 ml large volume plastic spacer, Volumatic (VM); and conventional Evohaler pMDI (EH). METHODS:Nineteen healthy volunteers completed the study using a randomised double blind, double dummy crossover design. Single doses of placebo or Seretide HFA 250 (total dose ex-valve: fluticasone 2000 mcg/salmeterol 200 mcg) were administered via SB, VM and EH. Overnight urinary cortisol creatinine (OUCC) and serum potassium (K) were measured at baseline and after each dose as systemic surrogates of relative respirable dose delivery for the fluticasone and salmeterol moieties, respectively. RESULTS: Significant suppression of OUCC and K occurred from baseline with SB and VM but not EH devices(geometric mean fold suppression, 95% CI, p and arithmetic mean fall mmol/L, 95% CI, respectively); EH:1.51(0.43-1.01), p 1/4 0.06; VM: 2.52(1.57-4.04), p < 0.001; SB: 2.66(1.57-4.49), p < 0.001(equating to 33.8%,60.2% and 62.3% falls, respectively). For K, the falls for EH were 0.09(0.25 to 0.07), p 1/4 0.69; VM: 0.27(0.46 to 0.08), p 1/4 0.003; SB: 0.32(0.53 to 0.11), p 1/4 0.002 (equating to 2.2%, 6.8%, and 8.06% fall,respectively). There were no significant differences between SB and VM. CONCLUSION: The breath-actuated Synchro-Breathe device was comparable to an optimally prepared Volumatic spacer, and resulted in commensurate improvement in relative lung bioavailability for both fluticasone and salmeterol moieties compared to pMDI.
RCT Entities:
BACKGROUND: Spacer devices facilitate respirable drug delivery. A novel breath-actuated antistatic spacer with integrated vortex chamber (Synchro-Breathe) device has been developed, which is compact,portable and user friendly as compared to conventional spacers which are bulky and cumbersome. The relative bioavailability to the lung of inhaled fluticasone and salmeterol combination is primarily dependent on respirable dose delivery and can be reliably quantified using adrenal suppression and early fall in serum potassium (marker of systemic beta-2 adrenoreceptor response) as surrogate markers for delivered lung dose. AIMS AND OBJECTIVES: To compare the in vivo relative bioavailability to the lung of Hydrofluoroalkane(HFA) Seretide delivered via Synchro-Breathe (SB); an optimally prepared 750 ml large volume plastic spacer, Volumatic (VM); and conventional Evohaler pMDI (EH). METHODS: Nineteen healthy volunteers completed the study using a randomised double blind, double dummy crossover design. Single doses of placebo or Seretide HFA 250 (total dose ex-valve: fluticasone 2000 mcg/salmeterol 200 mcg) were administered via SB, VM and EH. Overnight urinary cortisol creatinine (OUCC) and serum potassium (K) were measured at baseline and after each dose as systemic surrogates of relative respirable dose delivery for the fluticasone and salmeterol moieties, respectively. RESULTS: Significant suppression of OUCC and K occurred from baseline with SB and VM but not EH devices(geometric mean fold suppression, 95% CI, p and arithmetic mean fall mmol/L, 95% CI, respectively); EH:1.51(0.43-1.01), p 1/4 0.06; VM: 2.52(1.57-4.04), p < 0.001; SB: 2.66(1.57-4.49), p < 0.001(equating to 33.8%,60.2% and 62.3% falls, respectively). For K, the falls for EH were 0.09(0.25 to 0.07), p 1/4 0.69; VM: 0.27(0.46 to 0.08), p 1/4 0.003; SB: 0.32(0.53 to 0.11), p 1/4 0.002 (equating to 2.2%, 6.8%, and 8.06% fall,respectively). There were no significant differences between SB and VM. CONCLUSION: The breath-actuated Synchro-Breathe device was comparable to an optimally prepared Volumatic spacer, and resulted in commensurate improvement in relative lung bioavailability for both fluticasone and salmeterol moieties compared to pMDI.