Abstract
Tuberculosis treatment consists of a
drug combination, where
isoniazid is the core
drug and
alcoholism is a factor highly related to poor
patient compliance with the
therapy.
CYP2E1 is an
enzyme involved both in the
metabolism of
ethanol and in the formation of hepatotoxic compounds during the
metabolism of
isoniazid. The
shared metabolism pathway accounts for the possibility of pharmacokinetic interaction in cases of concomitant alcohol use during
tuberculosis treatment. The aim of this study was to evaluate the effect of repeated exposure of
Wistar rats (
males, 250 g, n=6) to
ethanol on the
pharmacokinetics of a
single dose of
isoniazid in combination with
pyrazinamide and
rifampicin (100 mg/kg, 350 mg/kg and 100 mg/kg, respectively). An
animal group received the combination of
drugs and
ethanol and was compared to a
control group, which received the combination of
drugs without exposure to
ethanol. The
plasma concentrations of
isoniazid were determined by a UHPLC/UV bioanalytical
method that was previously validated.
Biochemical markers of
liver function were measured to assess potential damage. A lower elimination
half-life of
isoniazid was observed in the
ethanol group than in the
control group (t1/2 0.91 h versus 1.34 h). There was no evidence of hepatotoxicity through the
biomarker enzymes evaluated. The results allow us to infer that although there are no biochemical changes related to
liver damage, there is a slight influence of
ethanol exposure on the pharmacokinetic profile of
isoniazid. This change may have a relevant impact on the
efficacy of
isoniazid in the outcome of
tuberculosis treatment.