Study objective: To use histamine bronchoprovocation
and bioassay statistical procedures to evaluate the in
vivo bioequivalence of a generic albuterol metered-dose inhaler
Design: A randomized, double-blind, balanced,
crossover design was used to determine the potency of each generic
albuterol MDI actuation relative to Ventolin (Glaxo Wellcome; Research
Triangle Park, NC) administration. One treatment was administered on
each of 4 study days. A histamine bronchoprovocation procedure was
initiated 1.25 h before and 15 min after administration of the
nonsmoking subjects with mild-to-moderate asthma were studied (18 to 65
years of age; FEV1, > 60% of predicted; and provocative
concentration of histamine causing a 20% fall in FEV1[
PC20], ≤ 8 mg/mL at screening).
Interventions: One and four actuations (90 and 360 μg,
respectively) of the generic MDI and of Ventolin MDI. Placebo inhalers
were used to maintain blinding of inhaler and doses.
Measurements and results: The primary outcome variable was
histamine PC20 measured after study treatment
administration. A significant dose-effect relationship was present
(p < 0.0001). Deviation from parallelism of the generic and Ventolin
dose-response curves (p = 0.95) and differences in overall mean
response between the two formulations (p = 0.68) were not
significant. Using Finney 2 × 2 bioassay statistical
procedures, we estimated that one actuation of the generic albuterol
MDI was equivalent to 1.01 puffs of Ventolin (90% confidence interval,
0.69 to 1.50).
Conclusion: The generic albuterol MDI
delivers a quantity of albuterol to the β2-receptor site
in the lung that is the bioequivalent to Ventolin. Further, this study
reinforces the validity of this statistical methodology for determining
in vivo bioequivalence.