Tags

Type your tag names separated by a space and hit enter

Relative bioavailability of rifampicin in a three-drug fixed-dose combination formulation.
Int J Tuberc Lung Dis. 2010 Nov; 14(11):1454-60.IJ

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 (C(max)), 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 (AUC(0-12h)) and 17.92 ± 10.66 and 68.43 ± 22.39 μg.h/ml for AUC up to time infinity (AUC(0-∞)). The test/reference ratio of the means (90%CI) was 25.36% (17.33-37.10) for C(max), 21.25% (14.61-30.89) for AUC(0-12h) and 22.08% (15.44-31.56) for AUC(0-∞). 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.

Authors+Show Affiliations

Facultad de Ciencias Químicas, Universidad Autónoma Metropolitana, Unidad Xochimilco, Mexico DF, Mexico. milanros@uaslp.mxNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20937187

Citation

Milán-Segovia, R C., et al. "Relative Bioavailability of Rifampicin in a Three-drug Fixed-dose Combination Formulation." The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease, vol. 14, no. 11, 2010, pp. 1454-60.
Milán-Segovia RC, Domínguez-Ramírez AM, Jung-Cook H, et al. Relative bioavailability of rifampicin in a three-drug fixed-dose combination formulation. Int J Tuberc Lung Dis. 2010;14(11):1454-60.
Milán-Segovia, R. C., Domínguez-Ramírez, A. M., Jung-Cook, H., Magaña-Aquino, M., Romero-Méndez, M. C., Medellín-Garibay, S. E., Vigna-Pérez, M., & Romano-Moreno, S. (2010). Relative bioavailability of rifampicin in a three-drug fixed-dose combination formulation. The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease, 14(11), 1454-60.
Milán-Segovia RC, et al. Relative Bioavailability of Rifampicin in a Three-drug Fixed-dose Combination Formulation. Int J Tuberc Lung Dis. 2010;14(11):1454-60. PubMed PMID: 20937187.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relative bioavailability of rifampicin in a three-drug fixed-dose combination formulation. AU - Milán-Segovia,R C, AU - Domínguez-Ramírez,A M, AU - Jung-Cook,H, AU - Magaña-Aquino,M, AU - Romero-Méndez,M C, AU - Medellín-Garibay,S E, AU - Vigna-Pérez,M, AU - Romano-Moreno,S, PY - 2010/10/13/entrez PY - 2010/10/13/pubmed PY - 2011/1/29/medline SP - 1454 EP - 60 JF - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease JO - Int. J. Tuberc. Lung Dis. VL - 14 IS - 11 N2 - 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 (C(max)), 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 (AUC(0-12h)) and 17.92 ± 10.66 and 68.43 ± 22.39 μg.h/ml for AUC up to time infinity (AUC(0-∞)). The test/reference ratio of the means (90%CI) was 25.36% (17.33-37.10) for C(max), 21.25% (14.61-30.89) for AUC(0-12h) and 22.08% (15.44-31.56) for AUC(0-∞). 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. SN - 1815-7920 UR - https://www.unboundmedicine.com/medline/citation/20937187/Relative_bioavailability_of_rifampicin_in_a_three_drug_fixed_dose_combination_formulation_ L2 - https://www.ingentaconnect.com/openurl?genre=article&issn=1027-3719&volume=14&issue=11&spage=1454&aulast=Milán-Segovia DB - PRIME DP - Unbound Medicine ER -