Assessment of Comparative Bioequivalence of Two Metered-Dose Inhaler Formulations of Salbutamol
- 92 Downloads
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.
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.
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.
KeywordsSalbutamol Mexico City Ventolin Peak Expiratory Flow Rate Pharmacodynamic Parameter
This study was supported by The Instituto Nacional de Enfermedades Respiratorias, México, and Escuela Superior de Medicina, Instituto Politécnico Nacional, México.
- 4.Byron PR. Inhalation devices. In: D’Arcy PF, McElnay JC, editors. The pharmacy and pharmacotherapy of asthma. Chichester: Ellis Horwood Ltd, 1989: 137–159Google Scholar
- 9.Global Initiative for Asthma. A practical guide for public health officials and health care professionals. Medical Communication Resources Inc. NIH publication No 96-3659A, 1995 DecGoogle Scholar
- 10.American Thoracic Society. Medical Section of the American Lung Association. Standarization of Spirometry [update]. 1994 Nov 11Google Scholar
- 12.Rowland M, Tozer TN. Clinical pharmacokinetics: concepts and applications. 2nd ed. Philadelphia: Lea & Febiger, 1989Google Scholar
- 14.Sanchis-Aldás J, Casan-Clara P, Castillo-Gómez J, et al. Espirometría Forzada. In: Caminero-Luna JA, Fernández-Fau L, editors. Recomendaciones SEPAR. Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Barcelona, 1998: 1–18Google Scholar
- 19.FDA 1996. Transcript of the Advisory Committee for Pharma-ceutical Science and Pulmonary-Allergy Drugs Advisory Committee Center for Drug Evaluation and Research, Food and Drug Administration. Washington: Associated Reporters of Washington, 1996 Aug 16Google Scholar