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

Allergy Asthma Proc. 2016 Sep;37(5):370-5. doi: 10.2500/aap.2016.37.3985. Epub 2016 Aug 12.

Abstract

Background: Many children struggle with the use of albuterol hydrofluoroalkane (HFA) inhalers. Albuterol multidose dry powder inhaler (MDPI) may simplify rescue bronchodilator use in children.

Objective: To compare the pharmacokinetics (PK), pharmacodynamics (PD), and tolerability of albuterol MDPI and albuterol HFA after a single inhaled dose in children with asthma.

Methods: 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.

Results: 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.

Conclusion: Albuterol MDPI and albuterol HFA had comparable PK and PD in children after a single 180-μg dose. ClinicalTrails.gov identifiers NCT01899144 and NCT02126839.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Albuterol / administration & dosage*
  • Albuterol / adverse effects
  • Albuterol / pharmacokinetics*
  • Asthma / diagnosis
  • Asthma / drug therapy*
  • Child
  • Child, Preschool
  • Dry Powder Inhalers*
  • Female
  • Humans
  • Male
  • Metered Dose Inhalers*
  • Respiratory Function Tests
  • Risk Factors
  • Treatment Outcome

Substances

  • Albuterol

Associated data

  • ClinicalTrials.gov/NCT01899144
  • ClinicalTrials.gov/NCT02126839