Comparative lung bioavailability of fluticasone/salmeterol via a breath-actuated spacer and conventional plastic spacers.
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.



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.



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).



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.
Asthma & Allergy Research Group, Division of Medical Sciences, Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, DD1 9SY.
Arun
A
Nair
Asthma & Allergy Research Group, Division of Medical Sciences, Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, DD1 9SY.
Lorna
L
McKinlay
Asthma & Allergy Research Group, Division of Medical Sciences, Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, DD1 9SY.
Peter
P
Williamson
Asthma & Allergy Research Group, Division of Medical Sciences, Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, DD1 9SY.
Philip
P
Short
Asthma & Allergy Research Group, Division of Medical Sciences, Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, DD1 9SY.
Patricia
P
Burns
Asthma & Allergy Research Group, Division of Medical Sciences, Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, DD1 9SY. brianlipworth@googlemail.com.
Brian J
BJ
Lipworth
D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000730:Androstadienes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D003404:Creatinine / Q000652:urine; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D036503:Inhalation Spacers; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood
D000730:Androstadienes; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D003404:Creatinine; D000420:Albuterol; D011188:Potassium; D006854:Hydrocortisone
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