Comparative lung bioavailability of fluticasone/salmeterol via a breath-actuated
spacer and conventional plastic spacers.
Author(s): Nair A, McKinlay L, Williamson P, Short P, Burns P, Lipworth BJ.
Affiliation(s): Asthma & Allergy Research Group, Division of Medical Sciences, Ninewells Hospital
& Medical School, University of Dundee, Dundee, Scotland. a.nair@dundee.ac.uk
Publication date & source: 2011, Eur J Clin Pharmacol. , 67(4):355-63
PURPOSE: This study compares the in vivo relative lung bioavailability of
Hydrofluoroalkane (HFA) Seretide delivered via unprimed and unwashed Aerochamber
Plus (AP) or Volumatic (VM) spacers, a integrated breath-actuated vortex
Synchro-Breathe (SB) device and an Evohaler pMDI (EH) device using adrenal
suppression and early fall in serum potassium (K) as surrogates for respirable
dose.
METHODS: Seventeen healthy volunteers completed this randomised double-blind,
double-dummy crossover study. Single doses of placebo/Seretide 250 (total dose ex
valve fluticasone 2000 mcg/salmeterol 200 mcg) were administered via the devices.
Overnight urinary cortisol/creatinine (OUCC) and serum K were measured at
baseline and after each dose.
RESULTS: Significant suppression of OUCC and K occurred from baseline with the
SB, AP and VM but not with the EH devices. The geometric mean fold suppression
(95% confidence interval, p) was: EH, 1.59 (0.80-3.14, p=0.40); AP, 4.26
(3.01-6.02, p<0.001); VM, 3.11 (1.99-4.78, p<0. 001); SB, 3.29 (2.04-5.24,
p<0.001). For K, the arithmetic mean fall (mmol/l) (95% confidence interval; p)
was: EH, -0.10 (-0.25-0.05, p=0.18); AP, -0.23 (-0.41 to -0.04, p=0.02); VM,
-0.22 (-0.44 to -0.01, p=0.04); SB, -0.28 (-0.42 to -0.13, p=0.001).
CONCLUSIONS: The breath-actuated SB device was comparable to 'out of the box'
small and large volume spacers and produced similar improvements in relative
systemic lung bioavailability for fluticasone and salmeterol.
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