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Preclinical Efficacy Testing of New Drug Candidates

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  • Author: Eric L. Nuermberger1
  • Editors: William R. Jacobs Jr.2, Helen McShane3, Valerie Mizrahi4, Ian M. Orme5
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21231-1002; 2: Howard Hughes Medical Institute, Albert Einstein School of Medicine, Bronx, NY 10461; 3: University of Oxford, Oxford OX3 7DQ, United Kingdom; 4: University of Cape Town, Rondebosch 7701, South Africa; 5: Colorado State University, Fort Collins, CO 80523
  • Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.TBTB2-0034-2017
  • Received 13 April 2017 Accepted 21 April 2017 Published 23 June 2017
  • E. L. Nuermberger, enuermb@jhmi.edu
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  • Abstract:

    This is a review of the preclinical efficacy testing of new antituberculosis drug candidates. It describes existing dynamic and models of antituberculosis chemotherapy and their utility in preclinical evaluations of promising new drugs and combination regimens, with an effort to highlight recent developments. Emphasis is given to the integration of quantitative pharmacokinetic/pharmacodynamic analyses and the impact of lesion pathology on drug efficacy. Discussion also includes models of chemotherapy of latent tuberculosis infection.

  • Citation: Nuermberger E. 2017. Preclinical Efficacy Testing of New Drug Candidates. Microbiol Spectrum 5(3):TBTB2-0034-2017. doi:10.1128/microbiolspec.TBTB2-0034-2017.

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/content/journal/microbiolspec/10.1128/microbiolspec.TBTB2-0034-2017
2017-06-23
2017-09-19

Abstract:

This is a review of the preclinical efficacy testing of new antituberculosis drug candidates. It describes existing dynamic and models of antituberculosis chemotherapy and their utility in preclinical evaluations of promising new drugs and combination regimens, with an effort to highlight recent developments. Emphasis is given to the integration of quantitative pharmacokinetic/pharmacodynamic analyses and the impact of lesion pathology on drug efficacy. Discussion also includes models of chemotherapy of latent tuberculosis infection.

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Figures

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FIGURE 1

Diagram of a hollow fiber system model of TB (HFS-TB) ( 49 ).

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.TBTB2-0034-2017
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Image of FIGURE 2
FIGURE 2

Schematic representation of various experimental models.

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.TBTB2-0034-2017
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Tables

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TABLE 1

New drugs in clinical development for the treatment of active TB, including ongoing clinical trials and the preclinical evidence base that supports each trial

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.TBTB2-0034-2017
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TABLE 2

Qualification opinion of the European Medicines Agency’s Committee for Medicinal Products for Human Use regarding the HFS-TB ( 48 )

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.TBTB2-0034-2017
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TABLE 3

Ranking of regimens to treat latent TB infection in the paucibacillary mouse model and correspondence with clinical guidelines

Source: microbiolspec June 2017 vol. 5 no. 3 doi:10.1128/microbiolspec.TBTB2-0034-2017

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