Isoniazid pharmacokinetic evaluation in ethanol exposed rats

• Grant number: 15/18509-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2016
• End date: December 31, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Rosangela Gonçalves Peccinini
• Grantee: Taísa Busaranho Franchin
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis that still in 2013 is responsible for 1.5 million of deaths. The treatment of tuberculosis consists in the use of the association of Isoniazid, Rifampin and Pyrazinamide for two months, followed by four months of Isoniazid and Rifampin. Although it is a very serious disease, tuberculosis can be completely cured if the treatment is followed correctly, but the long term treatment and the adverse effects as hepatotoxicity can lead to the abandonment of therapy. The isoniazid has hepatic metabolism and it is oxidized by the enzyme CYP2E1, where highly hepatotoxic compound is generated. Several reports in the literature show that a factor also associated to the abandonment of treatment it is the alcoholism. Alcohol has hepatic metabolism that occurs predominantly by the alcohol dehydrogenase path, only 10% of metabolism occurs by the Microsomal Ethanol Oxidizing System (MEOS), where the main enzyme involved with the oxidation of ethanol is CYP2E1, which suffers induction by your substrates. As CYP2E1 participates in the metabolism process of isoniazid and can have your levels increased with the use of alcohol, there are a probability of pharmacokinetic interaction when alcohol is used combined with the tuberculosis treatment. Therefore the present study intends to evaluate the effects to the use of ethanol on the pharmacokinetics parameters of isoniazid in a group of animals (Wistar rats) after a single dose administration of INH+RMP+PYR, the tuberculosis association treatment.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TAÍSA BUSARANHO FRANCHIN; JONATA AUGUSTO DE OLIVEIRA; CAROLINE DAMICO CANDIDO; EVELIN DOS SANTOS MARTINS; ELIAS CARVALHO PADILHA; MICHEL LEANDRO DE CAMPOS; ROSÂNGELA GONÇALVES PECCININI. Pharmacokinetics of isoniazid in Wistar rats exposed to ethanol. Brazilian Journal of Pharmaceutical Sciences, v. 58, 2023-01-16. (15/18509-2, 11/11239-9)