Pharmacokinetic Comparison of Inhaled Fixed Combination vs. the Free Combination of Beclomethasone and Formoterol pMDIs in Asthmatic Children

AIM: The fixed combination of Beclomethasone (BDP) and Formoterol pMDI (Foster®, Chiesi Farmaceutici) is being developed in the lower strength (BDP/Formoterol: 50/6μg) to provide an appropriate dosage in children with asthma. The aim of this work was to investigate the systemic bioavailability of B17MP (active metabolite of BDP) and Formoterol after single inhalation of Foster® pMDI 50/6μg vs. the free combination of BDP and Formoterol pMDIs in asthmatic children. METHODS: 5-11-year-old children inhaled BDP 200μg and Formoterol 24μg as fixed vs. free combination in an open label, randomized, 2-way crossover single dose study. Blood was collected pre-dose up to 8h post-dose for pharmacokinetic evaluation (AUC(0-t) , AUC(0-∞) , AUC(0-0.5h) , 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: 20 subjects were evaluable. The systemic exposure of B17MP and Formoterol administered as fixed combination did not exceed the free combination: B17MP AUC(0-t) (hours(2) pg/mL) ratio Test/Reference [90% CI], 0.81 [0.697-0.948] and Formoterol AUC(0-t) (hours(2) pg/mL) ratio Test/Reference 0.97 [0.85-1.10]. All pharmacokinetic and pharmacodynamic endpoints 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.