Pharmacokinetics and pharmacodynamics of albuterol multidose dry powder inhaler and albuterol hydrofluoroalkane in children with asthma

Abstract

Many children struggle with the use of albuterol hydrofluoroalkane (HFA) inhalers. Albuterol multidose dry powder inhaler (MDPI) may simplify rescue bronchodilator use in children. To compare the pharmacokinetics (PK), pharmacodynamics (PD), and tolerability of albuterol MDPI and albuterol HFA after a single inhaled dose in children with asthma. This single-center, open-label, two-period crossover study randomized children to albuterol MDPI or HFA 180 μg on two treatment days with a 4- to 14-day washout. Plasma albuterol concentrations were measured before the dose and up to 10 hours after the dose to determine the primary PK values of area under the plasma concentration-versus-time curve from time 0 to the last measurable concentration (AUC0-t), maximum observed concentration (Cmax), and AUC from time 0 extrapolated to infinity (AUC0-inf). Heart rate and blood pressure before the dose and after the dose were monitored for PD effects, and adverse events (AE) were monitored for overall safety. Fifteen children, ages 6-11 years, were included (PK, n = 13 for time to Cmax and terminal half-life of elimination; n = 12 for AUC and Cmax due to incomplete data). AUC0-t (geometric mean ratio [GMR] 1.056 [90% confidence interval {CI}, 0.88-1.268]) and AUC0-inf (GMR 0.971 [90% CI, 0.821-1.147]) were comparable between treatments. Cmax was larger for albuterol MDPI versus HFA (GMR 1.340 [90% CI, 1.098-1.636]). PD parameters between the treatments were comparable. No deaths, serious AEs, treatment-emergent AEs, or withdrawals due to AEs were reported for either treatment. Albuterol MDPI and albuterol HFA had comparable PK and PD in children after a single 180-μg dose. ClinicalTrails.gov identifiers NCT01899144 and NCT02126839.