Relative bioavailability of isoniazid in a fixed-Dose combination product in healthy Mexican subjects Article uri icon

abstract

  • SETTING: Subtherapeutic plasma isoniazid (INH) concentrations and the development of bacterial resistance may be attributed to poor quality and reduced bioavailability of fixed-dose combination (FDC) formulations. The bioavailability of INH from a generic and that of a branded FDC formulation had not been compared in the Mexican population. OBJECTIVE: To evaluate the bioequivalence of a generic three-drug FDC formulation (3FDC) in comparison with a 3FDC reference with doses of 300 mg INH in 20 healthy Mexican adults, and to generate data regarding the oral relative bioavailability of the drug in this population. DESIGN: A single-dose, randomised-sequence, openl abel, two-period crossover study. RESULTS: Both formulations were well tolerated. The pharmacokinetic parameters of INH showed wide interindividual variability. The average relative bioavailability calculated for maximum serum concentration area under the concentration-time curve (AUC), AUC0-24h and AUC0-∞ of the test 3FDC formulation vs. the 3FDC reference were respectively 64.84%25 (90%25CI 56.01-75.06), 59.05%25 (90%25CI 50.27-69.36) and 57.26%25 (90%25CI 46.93-69.84). CONCLUSIONS: The 3FDC test and reference formulations were not bioequivalent because the 90%25CI for the geometric mean ratios did not meet the regulatory requirements for bioequivalence (range 80-125%25) based on the rate and extent of absorption. © 2014 The Union.

publication date

  • 2014-01-01