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Assessment of Comparative Bioequivalence of Two Metered-Dose Inhaler Formulations of Salbutamol

Measuring Bronchodilatory Effect in Patients with Asthma

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Abstract

Objective

To compare the bioavailability of two metered-dose inhalers (MDIs) containing salbutamol (albuterol) by means of a spirometric evaluation of the time-course of bronchodilation in patients with moderate asthma.

Design and patients

25 asthmatic patients (12 males, 13 females) participated in the study. Study participants received salbutamol 200μg (Ventolin®, GlaxoSmithKline Mexico City, or Assal®, Salus SA de CV, Mexico City) on separate days according to a double-blind, crossover design. Spirometry was performed 30 minutes before and at selected times during the 8 hours following drug administration. The time-course of changes in forced expiratory volume in 1 second (FEV1) [transformed to individual percentage of maximal response] was used to compare the formulations. Pharmacodynamic parameters, maximal effect (Emax) and area under the percentage of response-time curve (AUC) were obtained and compared by analysis of variance, and ratios of AUC and Emax and 90% confidence limits were calculated.

Results

Values obtained for Emax were 94.81 ± 2.19% and 84.45 ± 3.44% for Ventolin® and Assal®, respectively, whereas values for AUC were 25 278 ± 1873 %·min and 18 155 ± 1806 %·min, respectively. Ratios were 89.1 and 71.8% with 90% confidence limits of 79.6 to 98.5% and 53.9 to 89.7% for Emax and AUC, respectively. The probability according to the two one-sided t-test of having values lower than 80% was higher than 0.05 for both AUC and Emax, indicating that the formulations tested are not bioequivalent.

Conclusions

It is concluded that this method is suitable for comparing the bio-availability of MDI formulations of bronchodilatory agents and that the formulations tested were not bioequivalent.

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Notes

  1. 1Tradenames are used for product identification only and do not imply endorsement.

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Acknowledgements

This study was supported by The Instituto Nacional de Enfermedades Respiratorias, México, and Escuela Superior de Medicina, Instituto Politécnico Nacional, México.

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Authors and Affiliations

  1. Instituto National de Enfermedades Respiratorias, Secretaría de Salud Mexico City, Mexico

    Héctor León-Molina, Francisco J. Flores-Murrieta &  Rocío Chapela

  2. Sectión de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico National, Mexico City, Mexico

    Francisco J. Flores-Murrieta

Authors
  1. Héctor León-Molina
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  2. Francisco J. Flores-Murrieta
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  3. Rocío Chapela
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Corresponding author

Correspondence to Rocío Chapela.

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León-Molina, H., Flores-Murrieta, F.J. & Chapela, R. Assessment of Comparative Bioequivalence of Two Metered-Dose Inhaler Formulations of Salbutamol. Clin. Drug Investig. 22, 435–441 (2002). https://doi.org/10.2165/00044011-200222070-00003

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