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Pharmacokinetic comparison of inhaled fixed combination vs . the free combination of beclomethasone and formoterol p MDI s in asthmatic children
Author(s) -
Chawes Bo L. K.,
Piccinno Annalisa,
KreinerMøller Eskil,
Vissing Nadja H.,
Poorisrisak Porntiva,
Mortensen Li,
Nilson Erik,
Bisgaard Amalie,
Dossing Anna,
Deleuran Maja,
Skytt Nanna L.,
Samandari Nasim,
Sergio Francesco,
Ciurlia Giorgia,
Poli Gianluigi,
Acerbi Daniela,
Bisgaard Hans
Publication year - 2013
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2012.04459.x
Subject(s) - formoterol , medicine , crossover study , pharmacokinetics , bioavailability , pharmacodynamics , pharmacology , dry powder inhaler , inhaler , asthma , bronchodilator , fixed dose combination , adverse effect , inhalation , anesthesia , budesonide , alternative medicine , pathology , placebo
Aim The fixed combination of beclomethasone ( BDP ) and formoterol pressurized metered dose inhaler (p MDI ) ( F oster®, C hiesi F armaceutici) 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 ( B 17 MP , the active metabolite of BDP ) and formoterol after single inhalation of F oster® p MDI 50/6 μg vs . the free combination of BDP and formoterol p MDI s 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 , C max , t max , t 1/2 ). 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 B 17 MP and formoterol administered as fixed combination did not exceed the free combination: B 17 MP 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.