Coutie, WJ

Dempsey, OJ

Lipworth, BJ

Wilson, AM

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 pmin 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

Dempsey, Owen J.

Wilson, Andrew M.

Coutie, Wendy J. R.

Lipworth, Brian J.

University of East Anglia digital repository

Evaluation of the effects of a large volume spacer on the systemic bioactivity of fluticasone propionate metered dose inhaler

Evaluation of the effects of a large volume spacer on the systemic bioactivity of fluticasone propionate metered dose inhaler

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University of East Anglia digital repository