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

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.

© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Figures

Figure 1

Mean B17MP plasma profiles from pre-dose (0 h) till 8 h post-dose by treatment: Foster® 50/6 μg pMDI fixed combination of BDP and formoterol (test, ) vs. the free combination of BDP and formoterol pMDI (reference, ). n = 20; LOQ = 50 pg ml−1

Figure 2

Mean formoterol plasma profiles from pre-dose (0 h) till 8 h post-dose by treatment: Foster® 50/6μg pMDI fixed combination of BDP and Formoterol (test, ) vs. the free combination of BDP and formoterol pMDI (reference, ). n = 20; LOQ = 2 pg ml−1

Figure 3

Mean profile diagram of heart rate from pre-dose (0 h) till 8 h post-dose by treatment: Foster® 50/6 μg pMDI fixed combination of BDP and formoterol (test, ) vs. the free combination of BDP and formoterol pMDI (reference, ). n = 20

Figure 4

Mean profile diagram of peak expiratory flow (PEF) from pre-dose (0 h) till 8 h post-dose by treatment: Foster® 50/6 μg pMDI fixed combination of BDP and formoterol (test, ) vs. the free combination of BDP and formoterol pMDI (reference, ). n = 20