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Clinical Investigations: ASTHMA |

Evaluation of the Effect of a Large Volume Spacer on the Systemic Bioactivity of Fluticasone Propionate Metered-Dose Inhaler*

Owen J. Dempsey, MD; Andrew M. Wilson, MD; Wendy J. R. Coutie, HNC; Brian J. Lipworth, MD
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*From the Department of Clinical Pharmacology & Therapeutics, Ninewells Hospital & Medical School, University of Dundee, Scotland, UK.

Correspondence to: Brian J. Lipworth, MD, Professor of Allergy & Respiratory Medicine, Department of Clinical Pharmacology & Therapeutics, Ninewells Hospital & Medical School, Dundee, Scotland, UK; e-mail: b.j.lipworth@dundee.ac.uk.



Chest. 1999;116(4):935-940. doi:10.1378/chest.116.4.935
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Background: Inhaled corticosteroids such as fluticasone propionate (FP) have dose-related systemic effects, including adrenal suppression. We have therefore investigated the effect of adding a large volume spacer on the systemic bioactivity of FP given via a pressurized metered-dose inhaler (pMDI).

Methods: Fourteen healthy volunteers (mean age, 29.9 years old) were studied using an open, randomized, placebo-controlled, three-way crossover design. Single doses of the following were given at 5:00 pm in a randomized sequence: (1) eight puffs of FP by pMDI, 1.76 mg (250μ g ex-valve, 220 μg ex-actuator); (2) eight puffs of FP by pMDI, 250 μg, with 750-mL spacer (Volumatic; Allen & Hanburys; Uxbridge, UK); and (3) eight puffs of placebo by pMDI. Measurements were made after each dose, including overnight and early morning urinary cortisol/creatinine ratios and 8:00 am serum cortisol.

Results: Significant (p < 0.05) suppression of all three end points occurred with each active treatment compared to treatment with placebo. Furthermore, significant (p < 0.05) additional suppression occurred when comparing FP by pMDI alone to FP by pMDI with spacer. Geometric mean fold differences (95% confidence interval for fold difference) between FP by pMDI alone and FP by pMDI with spacer were 1.94-fold (1.00–3.78) for overnight urinary cortisol/creatinine ratio and 1.98-fold (1.26–3.10) for 8:00 am serum cortisol. This was mirrored by a twofold rise in the number of values for uncorrected overnight urinary cortisol < 10 nmol/10 h: placebo treatment (none of 14 subjects); FP by pMDI (6 of 14 subjects; 43%); and FP by pMDI with spacer (12 of 14 subjects; 86%).

Conclusions: The use of a large volume spacer with FP by pMDI results in a twofold increase in the systemic bioavailability as assessed by sensitive measures of adrenal suppression. This, in turn, reflects a twofold improvement in respirable dose delivery with the spacer device.

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