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

TY - JOUR

T1 - Comparative lung bioavailability of fluticasone/salmeterol via a breath-actuated spacer and conventional plastic spacers

AU - Nair, Arun

AU - McKinlay, Lorna

AU - Williamson, Peter

AU - Short, Philip

AU - Burns, Patricia

AU - Lipworth, Brian J.

PY - 2011/4

Y1 - 2011/4

N2 - 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.

AB - 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.

KW - Asthma

KW - Lung bioavailability

KW - Fluticasone

KW - Salmeterol

KW - Seretide

KW - Spacer

KW - Metered dose inhaler

KW - Healthy subjects

KW - Systemic bioactivity

KW - Asthmatic patients

KW - Propionate

KW - Salbutamol

KW - Salmeterol

KW - Pharmacokinetics

KW - Device

KW - Corticosteroids

U2 - 10.1007/s00228-010-0989-9

DO - 10.1007/s00228-010-0989-9

M3 - Article

C2 - 21240480

SN - 0031-6970

VL - 67

SP - 355

EP - 363

JO - European Journal of Clinical Pharmacology

JF - European Journal of Clinical Pharmacology

IS - 4

ER -