Is the efflux pump inhibitor Verapamil a potential booster for isoniazid against Mycobacterium tuberculosis?



Título del documento: Is the efflux pump inhibitor Verapamil a potential booster for isoniazid against Mycobacterium tuberculosis?
Revue: Brazilian Journal of Pharmaceutical Sciences
Base de datos: PERIÓDICA
Número de sistema: 000451321
ISSN: 1984-8250
Autores: 1
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2
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Instituciones: 1Universidade Estadual de Maringa, Programa de Pos-Graduacao em Biociencias e Fisiopatologia, Maringa, Parana. Brasil
2Universidade Estadual de Maringa, Programa de Pos-graduacao em Ciencias da Saude, Maringa, Parana. Brasil
3Universidade Estadual Paulista "Julio de Mesquita Filho", Escola de Ciencias Farmaceuticas, Araraquara, Sao Paulo. Brasil
Año:
Volumen: 56
País: Brasil
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Experimental, aplicado
Resumen en inglés The membrane-based efflux pump systems are recognized to have an important role in pathogenicity and drug resistance in Mycobacterium tuberculosis by the extrusion of toxic substrates and drugs from the inner bacillus. This study aimed to investigate the in vitro interaction of Verapamil (VP), an efflux pump inhibitor, with the classical first-line anti-tuberculosis drug isoniazid (INH) in resistant and susceptible M. tuberculosis clinical isolates. Seven multidrug-resistant (MDR), three INH monoresistant and four susceptible M. tuberculosis clinical isolates were tested for the INH and VP combination by modified Resazurin Microtiter Assay Plate (REMA). Fractional Inhibitory Concentration (FIC) and Modulation Factor (MF) were determined. The INH plus VP combination showed no significant change in the Minimum inhibitory concentration (MIC) values of INH (FIC≥ 0.5; MF=1 or 2).The use of VP in tuberculosis therapy should be managed carefully, considering the resistance caused by specific mutation in katG and inhA genes, in which the use of these EPIs may have no success. The use of EPIs as an adjunctive drug in the anti-tuberculosis therapy should be further investigated on a larger number of M. tuberculosis clinical isolates with different resistant profile
Disciplinas: Medicina,
Química
Palabras clave: Farmacología,
Microbiología,
Tuberculosis,
Resistencia a fármacos,
Sinergismo,
Verapamil,
Isoniazida,
Mycobacterium tuberculosis
Keyword: Pharmacology,
Microbiology,
Tuberculosis,
Mycobacterium tuberculosis,
Multidrug resistance,
Synergism,
Verapamil,
Isoniazid
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