Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children

Authors

  • Bo L. K. Chawes,

    1. Copenhagen University Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte, Denmark
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  • Annalisa Piccinno,

    1. Corporate Clinical Development, Chiesi Farmaceutici S.p.A., Parma, Italy
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  • Eskil Kreiner-Møller,

    1. Copenhagen University Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte, Denmark
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  • Nadja H. Vissing,

    1. Copenhagen University Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte, Denmark
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  • Porntiva Poorisrisak,

    1. Copenhagen University Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte, Denmark
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  • Li Mortensen,

    1. Copenhagen University Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte, Denmark
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  • Erik Nilson,

    1. Copenhagen University Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte, Denmark
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  • Amalie Bisgaard,

    1. Copenhagen University Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte, Denmark
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  • Anna Dossing,

    1. Copenhagen University Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte, Denmark
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  • Maja Deleuran,

    1. Copenhagen University Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte, Denmark
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  • Nanna L. Skytt,

    1. Copenhagen University Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte, Denmark
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  • Nasim Samandari,

    1. Copenhagen University Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte, Denmark
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  • Francesco Sergio,

    1. Corporate Clinical Development, Chiesi Farmaceutici S.p.A., Parma, Italy
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  • Giorgia Ciurlia,

    1. Corporate Clinical Development, Chiesi Farmaceutici S.p.A., Parma, Italy
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  • Gianluigi Poli,

    1. Corporate Clinical Development, Chiesi Farmaceutici S.p.A., Parma, Italy
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  • Daniela Acerbi,

    1. Corporate Clinical Development, Chiesi Farmaceutici S.p.A., Parma, Italy
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  • Hans Bisgaard

    Corresponding author
    • Copenhagen University Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte, Denmark
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Correspondence

Professor Hans Bisgaard, Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte Ledreborg Allé 34, 2820 Gentofte, Denmark.

Tel.: +45 3977 7360

Fax: +45 3977 7129

E-mail: bisgaard@copsac.com

Website: http://www.copsac.com

Abstract

Aim

The fixed combination of beclomethasone (BDP) and formoterol pressurized metered dose inhaler (pMDI) (Foster®, Chiesi Farmaceutici) is being developed in the lower strength (BDP/formoterol: 50/6 μg) to provide an appropriate dosage for children with asthma. The aim of this work was to investigate the systemic bioavailability of beclomethasone-17-monoproprionate (B17MP, the active metabolite of BDP) and formoterol after single inhalation of Foster® pMDI 50/6 μg vs. the free combination of BDP and formoterol pMDIs in asthmatic children.

Methods

Children aged 5–11 years old inhaled BDP 200 μg and formoterol 24 μg as fixed vs. free combination in an open label, randomized, two way crossover single dose study. Blood was collected pre-dose up to 8 h post-dose for pharmacokinetic evaluation (AUC(0,t), AUC(0,∞), AUC(0,0.5 h, Cmax, tmax, t1/2). Pharmacodynamics included heart rate, plasma potassium, urinary glucose and cortisol excretion. Peak expiratory flow and adverse events were monitored.

Results

Twenty subjects were evaluable. The systemic exposure of B17MP and formoterol administered as fixed combination did not exceed the free combination: B17MP AUC(0,t) (pg ml−1 h) ratio test : reference (90% CI), 0.81 (0.697, 0.948) and formoterol AUC(0,t) (pg ml−1 h) ratio test : reference 0.97 (0.85, 1.10). All pharmacokinetic and pharmacodynamic end points showed non-superiority in favour of the test drug. One adverse event (vertigo) occurred but was not considered treatment-related.

Conclusion

BDP and formoterol pharmacokinetic and pharmacodynamic effects are non-superior after administration of the two actives as fixed vs. the free combination in 5–11-year-old asthmatic children.

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