In vivo comparison of the relative systemic bioavailability of fluticasone propionate from three anti-static spacers and a metered dose inhaler

Arun Nair, Daniel Menzies, Pippa Hopkinson, Lesley McFarlane, Brian J. Lipworth

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    Conventional spacers help overcome problems with co-ordination and may improve lung deposition and decrease oropharyngeal impaction.

     Antistatic spacers eliminate electrostatic charge and may hence improve respirable dose delivery.

    The systemic bioavailability of inhaled fluticasone propionate is primarily dependent on delivery by the pulmonary route and hence the performance of antistatic spacers can be evaluated using adrenal suppression as a sensitive surrogate for relative bioavailability to the lung after an inhalation.


     This study compares the relative bioavailability to the lung of inhaled fluticasone delivered via conventional pressurized metered dose inhalers (pMDI) and three antistatic spacers (plastic Zerostat-V, plastic Aerochamber Max, and metal Nebuchamber) in patients with asthma.

     All three antistatic spacers when compared with pMDI significantly increased the relative bioavailability to the lungs of inhaled fluticasone in terms of relative adrenal suppression, and there were no significant differences between the plastic and metal antistatic spacers.

    The systemic bioavailability of inhaled fluticasone propionate (FP) depends primarily on lung absorption and can be quantified by measuring suppression of overnight and early morning urinary cortisol/creatinine (OUCC and EMUCC, respectively). The aim of the study was to determine the relative bioavailability of hydrofluoroalkane (HFA) FP to the lungs via anti-static plastic (Zerostat-V and Aerochamber Max), metal (Nebuchamber) anti-static spacers and metered dose inhaler [Flixotide Evohaler (EH) (pMDI)].

    A randomized, double-blind, double-dummy, four-way crossover design was used. Eighteen mild to moderate asthmatics received single doses of placebo/HFA-FP 2 mg via the 280-ml Zerostat-V (ZS); 250-ml Nebuchamber (NC); 197-ml Aerochamber Max (AC); and pMDI (EH). Measurements of OUCC and EMUCC were made at baseline and 10 h after each dose.

    Significant suppression of OUCC and EMUCC occurred from baseline with all three spacers, but not Evohaler (geometric mean fold suppression, 95% confidence interval): ZS, 2.74 (1.75, 4.30), P < 0.001; NC, 3.31 (1.81, 6.06), P < 0.001; AC, 4.98 (3.39, 7.31), P < 0.001; and for EH this was 1.42 (0.92, 2.21), P = 0.169 (equating to a 64, 70, 80 and 30% fall in OUCC via the ZS, NC, AC and EH devices, respectively). There were significant differences between all three spacers vs. EH. When compared with the Evohaler, the Zerostat V resulted in 48% greater suppression (P = 0.009); the Nebuchamber 57% greater suppression (P = 0.001); and the Aerochamber Max 71% greater suppression of OUCC (P < 0.001).

    All three antistatic spacers significantly increased the relative systemic bioavailability of HFA-FP compared with the standard pMDI.

    Original languageEnglish
    Pages (from-to)191-198
    Number of pages8
    JournalBritish Journal of Clinical Pharmacology
    Issue number2
    Publication statusPublished - Feb 2009


    • Adrenal suppression
    • Antistatic spacers
    • Asthma
    • Fluticasone propionate
    • Asthmatic patients
    • Corticosteroids
    • Delivery
    • Devices
    • Formulations
    • Bioactivity
    • Salbutamol
    • Inhalation
    • Children
    • Charge

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