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Relative bioavailability of isoniazid in a fixed-dose combination product in healthy Mexican subjects

R C Milán-Segovia1, M Vigna-Pérez1, M C Romero-Méndez1

  • 1Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México.

The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease
|December 25, 2013
PubMed
Abstract

Insights

A generic fixed-dose combination formulation of isoniazid (INH) was not bioequivalent to the reference product in healthy Mexican adults. This finding suggests potential issues with drug bioavailability and raises concerns for tuberculosis treatment efficacy.

Area of Science:

  • Pharmacokinetics and Bioavailability
  • Tuberculosis Treatment
  • Pharmaceutical Formulation Analysis

Background:

  • Subtherapeutic isoniazid (INH) concentrations from fixed-dose combination (FDC) formulations may lead to bacterial resistance.
  • Previous studies have not compared the bioavailability of INH from generic and branded FDC formulations in the Mexican population.

Purpose of the Study:

  • To evaluate the bioequivalence of a generic three-drug FDC formulation (3FDC) against a reference 3FDC containing 300 mg INH.
  • To assess the oral relative bioavailability of INH in healthy Mexican adults.

Main Methods:

  • A single-dose, randomized-sequence, open-label, two-period crossover study was conducted.
  • Twenty healthy Mexican adults participated in the study.

Main Results:

  • Both INH formulations were well tolerated, with wide inter-individual pharmacokinetic variability observed.
  • The average relative bioavailability of the generic 3FDC compared to the reference was significantly lower, with geometric mean ratios for AUC(0-24h) and AUC(0-∞) falling outside the bioequivalence range.

Conclusions:

  • The generic 3FDC formulation was not bioequivalent to the reference formulation.
  • The observed lower bioavailability suggests potential risks for achieving therapeutic INH concentrations and managing tuberculosis in the Mexican population.

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