AIM: To investigate the pharmacokinetics and pharmacodynamics of an extrafine pressurized metered-dose inhaler (pMDI) fixed combination of beclometasone-dipropionate (BDP)/formoterol-fumarate (FF) in adolescent and adult asthma.

METHODS: Three-way crossover study, on 30 asthmatic adolescents receiving BDP/FF-pMDI with or without valved holding chamber (VHC) or a free licenced combination of BDP-pMDI and FF-pMDI; plus a parallel arm of 30 asthmatic adults receiving BDP/FF-pMDI. All patients received a single dose of BDP and FF of 400 µg and 24 µg, for each treatment, respectively. Assessments were performed over 8 hours.

RESULTS: In adolescents, the 90% confidence intervals (CIs) for the systemic exposure (AUC0-t ) geometric mean ratio of the fixed combination with or without VHC versus the free combination were within the bioequivalence range 0.80-1.25, both for beclometasone-17-monopropionate (B17MP, active metabolite of BDP) and formoterol. Pharmacodynamic variables for plasma potassium and glucose, pulse rate and pulmonary function in adolescents were equivalent between treatments; 95%CI within 0.94-1.09. The upper level of 90%CIs for AUC0-t geometric mean ratio adolescents/adults of B17MP and formoterol after treatment with BDP/FF-pMDI were lower than 1.25; 90%CI 0.78-1.04 and 0.86-1.17, respectively.

CONCLUSIONS: In adolescents the pharmacodynamics and the overall systemic exposure to the active ingredients of an extrafine fixed combination of BDP/FF-pMDI with or without VHC was equivalent to that of a free licenced combination pMDIs of established safety and efficacy profiles. The systemic exposure in adolescents was not higher than in adults. These results support the indication for use of inhaled-corticosteroids/long acting β2-agonists pMDIs in adolescents at the same dosage as in adults.