Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8485296 | Tuberculosis | 2016 | 19 Pages |
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 μM), inhibition of Mycobacterium tuberculosis growth occurred at total drug concentrations of â¥16 μg/ml, whereas in whole blood cultures (albumin concentration = 350 μM), â¥128 μg/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.
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Authors
Elizabeth P. Harausz, Keith A. Chervenak, Caryn E. Good, Michael R. Jacobs, Robert S. Wallis, Manuel Sanchez-Felix, W. Henry Boom, TB Research Unit (TBRU) at Case Western Reserve University TB Research Unit (TBRU) at Case Western Reserve University,