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Updated: Jul 11, 2026

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis
Published on: April 5, 2017
The effect of rifampicin and pyrazinamide on isoniazid pharmacokinetics in rats
Helen M Baldan1, Helene J De Rosa, Iguatemy L Brunetti
1Departamento de Princípios Ativos Naturais e Toxicologia, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, SP, Brasil.
Abstract:
Tuberculosis chemotherapy involves combination of the drugs isoniazid (INH), rifampicin (RMP) and pyrazinamide (PYR) for a 6-month period. The present work investigated the influence of RMP and PYR on the pharmacokinetic parameters of INH when groups of rats were pre-treated for 21 days with INH alone or in combination with RMP and/or PYR, in the following amounts per kg body weight: INH 100 mg; INH 100 mg+RMP 100 mg; INH 100 mg+PYR 350 mg; INH 100 mg+PYR 350 mg+RMP 100 mg. It was found that the co-administration of PYR caused an increase in the INH distribution volume (V(d)/F), half-life of elimination (t(1/2beta)) and clearance (Cl(T)/F), and a decrease in the area under curve 0 to 24 h (AUC). Co-administration of RMP caused an increase in the Cl(T)/F and a decrease in the AUC. The combination INH+PYR+RMP caused an increase in the Cl(T)/F and a decrease in the AUC. These significant pharmacokinetic interactions between the tuberculostatic drugs might be related to differences in the therapeutic and toxic effects.
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