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Free Content Relative bioavailability of rifampicin in a three-drug fixed-dose combination formulation

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Abstract:

SETTING: In a previous monitoring study of rifampicin (RMP) in tuberculosis (TB) patients treated with a generic formulation of a three-drug fixed-dose combination (3FDC), very low RMP levels were found. This led us to investigate the bioavailability of the product.

OBJECTIVE: To investigate the relative bioavailability of RMP from a generic 3FDC formulation used in the Mexican health care system, in comparison to the reference product, in healthy volunteers.

DESIGN: Two-period, two-sequence crossover study.

RESULTS: Mean pharmacokinetic parameter values obtained for the test and reference product were respectively 3.13 ± 2.01 μg/ml and 9.95 ± 2.66 μg/ml for peak plasma concentration (Cmax), 15.51 ± 9.77 μg.h/ml and 58.03 ± 16.1 μg.h/ml for area under the concentration (AUC) time curve to the last measurable concentration (AUC0–12h) and 17.92 ± 10.66 and 68.43 ± 22.39 μg.h/ml for AUC up to time infinity (AUC0–∞). The test/reference ratio of the means (90%CI) was 25.36% (17.33–37.10) for Cmax, 21.25% (14.61–30.89) for AUC0–12h and 22.08% (15.44–31.56) for AUC0–∞. These results did not meet the criteria for bioequivalence.

CONCLUSION: The test product displayed delayed absorption and markedly inferior RMP bioavailability in comparison to the reference product. RMP-containing generic formulations should only be used if their bioavailability has been evaluated to ensure interchangeability with the reference product and to avoid the risk of markedly inferior RMP exposure through the use of such a product.

Keywords: fixed-dose combinations; relative bioavailability; rifampicin

Document Type: Regular Paper

Affiliations: 1: Universidad Autónoma Metropolitana, Unidad Xochimilco, Mexico DF, Mexico; and Facultad de Ciencias Químicas, Universidad Autónoma de San Luís Potosí, San Luis Potosí, Mexico 2: Universidad Autónoma Metropolitana, Unidad Xochimilco, Mexico DF, Mexico 3: Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, Mexico 4: Hospital Central ‘Dr Ignacio Morones Prieto’ Secretaría de Salud, San Luis Potosí, Mexico 5: Facultad de Ciencias Químicas, Universidad Autónoma de San Luís Potosí, San Luis Potosí, Mexico

Publication date: November 1, 2010

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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