Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of Albuterol (Salbuterol) Multi-dose Dry-Powder Inhaler and ProAir(®) Hydrofluoroalkane for the Treatment of Persistent Asthma: Results of Two Randomized Double-Blind Studies.

BACKGROUND AND OBJECTIVE: Metered-dose inhalers require patients to coordinate inhalation with actuation. The present albuterol multi-dose dry-powder inhaler (mDPI) does not require patients to coordinate inspiration with actuation, thereby simplifying delivery of albuterol to the lungs. The aim of the present study was to compare the efficacy, pharmacokinetics, pharmacodynamics, extrapulmonary pharmacodynamics, and safety of albuterol (salbuterol) delivered via a ProAir® hydrofluoroalkane (HFA) metered-dose inhaler and an mDPI. METHODS: Two double-blind, randomized, double-dummy, crossover, multicenter, placebo-controlled studies in persistent asthma patients were conducted. Study 1: 47 adult patients were treated with cumulative doses of albuterol mDPI or ProAir HFA (90 µg/inhalation; 1 + 1 + 2 + 4 + 8 inhalations) or placebo. Study 2: 71 patients aged ≥12 years were randomly assigned to receive 90 or 180 µg of albuterol mDPI or ProAir HFA, or placebo. Primary efficacy endpoints were baseline-adjusted forced expiratory volume in 1 s (FEV1) at 30 min (30-min FEV1) after each cumulative dose (Study 1) and FEV1 area under the effect curve over 6 h (FEV1 AUEC0-6) after dosing (Study 2). RESULTS: Study 1: differences, with corresponding 90% confidence intervals, between albuterol mDPI and ProAir HFA in FEV1 after each cumulative dose and in FEV1 AUEC0-6 after the final dose were within pre-established equivalence limits. The difference in FEV1 at high vs. low doses was significant for both active treatments (p < 0.0001). Active treatments were similar in systemic exposure, extrapulmonary pharmacodynamics, and safety. Study 2: mean FEV1 AUEC0-6 was significantly greater than for placebo for both doses of albuterol mDPI and ProAir HFA (p < 0.0001). Albuterol mDPI was comparable to ProAir HFA at 90 and 180 µg. Both study treatments were generally well tolerated. CONCLUSION: The bronchodilatory efficacy and pharmacokinetic/pharmacodynamic profiles of albuterol mDPI and ProAir HFA are comparable, with a safety profile consistent with that of inhaled albuterol.

Medical costs and adherence in patients receiving aqueous versus pressurized aerosol formulations of intranasal corticosteroids.

Intranasal corticosteroid (INS) formulations have different sensory attributes that influence patient preferences, and thereby possibly adherence and health outcomes. This study compares health care use and costs and medication adherence in matched cohorts of patients with allergic rhinitis (AR) using a chlorofluorocarbon-propelled pressurized metered-dose inhaler (pMDI) or aqueous intranasal corticosteroid (A-INS). Florida Medicaid retrospective claims analysis was performed of enrollees aged ≥12 years with at least 1 year of continuous enrollment before their initial AR diagnosis, 1 year for continuous enrollment before their index INS claim, and 18 months of continuous enrollment after their index INS claim during which they received either pMDI or A-INS. pMDI and A-INS patients were matched 1:2 using propensity scores. Nonparametric analyses compared outcomes between matched cohorts at 6, 12, and 18 months of follow-up. A total of 585 patients were matched (pMDI = 195, A-INS = 390). pMDI patients were more adherent to INS, as reflected in their higher median medication possession ratio (53.2% versus 32.7%; p < 0.0001) and fewer median days between fills (73 days versus 111 days; p = 0.0003). Significantly lower median per patient pharmacy fills (34.0 versus 50.5; p < 0.05) and costs ($1282 versus $2178; p < 0.01) were observed among pMDI patients versus A-INS patients 18 months after INS initiation and were maintained when analyses excluded INS fills. Adherence to INS and health care utilization and costs following INS initiation for AR differed by type of formulation received. Our findings suggest patient preferences for INS sensory attributes can drive adherence and affect disease control, and ultimately impact health care costs.