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Demonstration of In Vivo Bioequivalence of a Generic Albuterol Metered-Dose Inhaler to Ventolin

2000; Elsevier BV; Volume: 117; Issue: 3 Linguagem: Inglês

10.1378/chest.117.3.714

1931-3543

B. A. Stewart, Richard C. Ahrens, Steve Carrier, Michael Frosolono, Cheri Lux, Seung-Ho Han, Gary Milavetz,

Pharmaceutical studies and practices

Study objective To use histamine bronchoprovocation and bioassay statistical procedures to evaluate the in vivo bioequivalence of a generic albuterol metered-dose inhaler (MDI). 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 study treatment. Patients Twenty-four 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. To use histamine bronchoprovocation and bioassay statistical procedures to evaluate the in vivo bioequivalence of a generic albuterol metered-dose inhaler (MDI). 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 study treatment. Twenty-four 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). 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. 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). 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.