Pharmacokinetics of isoniazid in Wistar rats exposed to ethanol

Authors

  • Taísa Franchin Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, São Paulo, Brazil
  • Jonata Augusto Oliveira Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, São Paulo, Brazil
  • Caroline Candido Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, São Paulo, Brazil
  • Evelin Martins Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, São Paulo, Brazil
  • Elias Padilha Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, São Paulo, Brazil https://orcid.org/0000-0002-3794-9389
  • Michel De Campos Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, São Paulo, Brazil; Health Sciences Institute, Federal University of Mato Grosso, Sinop, Mato Grosso, Brazil
  • Rosangela Gonçalves Peccinini Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, São Paulo, Brazil

DOI:

https://doi.org/10.1590/s2175-97902022e18881

Keywords:

Isoniazid, Ethanol, Pharmacokinetic interaction, Bioanalytical Method, Tuberculosis

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.

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Published

2023-02-16

Issue

Vol. 58 (2022)

Section

Original Article

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How to Cite

Pharmacokinetics of isoniazid in Wistar rats exposed to ethanol. (2023). Brazilian Journal of Pharmaceutical Sciences, 58. https://doi.org/10.1590/s2175-97902022e18881

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