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Comparative bioavailability of rifampicin and isoniazid in fixed-dose combinations and single-drug formulations.

The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease (2014-12-18)
L-H Hao, S-C Guo, C-C Liu, H Zhu, B Wang, L Fu, M-T Chen, L Zhou, J-Y Chi, W Yang, W-J Nie, Y Lu
ABSTRACT

The bioavailability of rifampicin (RMP) decreases by ∼30% on interaction with isoniazid (INH) in stomach acid conditions, which can result in the development of drug resistance and treatment failure. To compare the bioavailability in healthy volunteers of five anti-tuberculosis fixed-drug combinations (FDCs) used in China (formulations A-E) containing RMP and INH against single-drug formulations taken as reference. Two- or three-period, two- or three-sequence crossover study of drugs. Only RMP formulation E passed the bioequivalence criteria, with 90% confidence intervals for the log-transformed ratios of AUC₀₋₂₄, AUC₀₋∞, and Cmax of respectively 89.9-103.7, 89.6-102.2 and 87.7-107.9. For INH, formulations A, B, C and D passed the bioequivalence test, but not product E, where the 90%CIs of the log-transformed ratios of AUC₀₋₂₄, AUC₀₋∞, and Cmax were respectively 85.2-100.7, 85.2-100.7 and 73.8-100.9. According to the results of the bioequivalence analysis carried out in this study, RMP formulations A, B, C and D were not within the acceptable range and only formulation E passed the bioequivalence criteria of 80-125%. In comparison, four-test INH formulations (A, B, C and D) were bioequivalent to the corresponding single-drug formulation, while product E failed in the bioequivalence criteria.

MATERIALS
Product Number
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Product Description

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