Redox Imbalance and Oxidative DNA Damage During Isoniazid Treatment of HIV-Associated Tuberculosis: A Clinical and Translational Pharmacokinetic Study.

ABSTRACT:

Background

The potential for hepatotoxicity during isoniazid-based tuberculosis (TB) treatment presents a major challenge for TB control programs worldwide. We sought to determine whether pharmacokinetic exposures of isoniazid and its metabolites were related to cellular oxidation/reduction status and downstream markers of oxidative DNA damage.

Methods

We performed intensive pharmacokinetic sampling among isoniazid-treated patients to determine the relative plasma exposures of isoniazid, acetylisoniazid, hydrazine, and acetylhydrazine. Physiologically-based pharmacokinetic modeling was used to estimate liver tissue exposures during a 24-h dosing interval for each compound. We experimentally treated HepG2 cells with isoniazid and metabolites at equimolar concentrations corres

SUBMITTER: Zentner I 

PROVIDER: S-EPMC7406860 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature