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Activity of nitazoxanide and tizoxanide against Mycobacterium tuberculosis in vitro and in whole blood culture.

ABSTRACT: Nitazoxanide (NTZ) and its metabolite tizoxanide (TIZ) were studied as antimycobacterial agents in vitro (in mycobacterial growth indicator tube [MGIT] cultures) and in a whole blood bactericidal assay. Both NTZ and TIZ show high protein binding. In MGIT cultures (albumin concentration = 78 ?M), inhibition of Mycobacterium tuberculosis growth occurred at total drug concentrations of ?16 ?g/ml, whereas in whole blood cultures (albumin concentration = 350 ?M), ?128 ?g/ml was required. Free drug fractions at these two conditions were estimated to be 69% and 2%, respectively. Co-incubation of NTZ and TIZ in human plasma for 72 h nearly completely eliminated their ability to inhibit mycobacterial growth in MGIT. Interactions with plasma proteins may limit the potential of NTZ and TIZ as drugs for human tuberculosis.

SUBMITTER: Harausz EP

PROVIDER: S-EPMC4864490 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Activity of nitazoxanide and tizoxanide against Mycobacterium tuberculosis in vitro and in whole blood culture.

Harausz Elizabeth P EP Chervenak Keith A KA Good Caryn E CE Jacobs Michael R MR Wallis Robert S RS Sanchez-Felix Manuel M Boom W Henry WH

Tuberculosis (Edinburgh, Scotland) 20160322

Nitazoxanide (NTZ) and its metabolite tizoxanide (TIZ) were studied as antimycobacterial agents in vitro (in mycobacterial growth indicator tube [MGIT] cultures) and in a whole blood bactericidal assay. Both NTZ and TIZ show high protein binding. In MGIT cultures (albumin concentration = 78 μM), inhibition of Mycobacterium tuberculosis growth occurred at total drug concentrations of ≥16 μg/ml, whereas in whole blood cultures (albumin concentration = 350 μM), ≥128 μg/ml was required. Free drug fr ...[more]

PMID: 27156623

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