Measurement of the Intracellular Mycobacterium tuberculosis Drug Effect and Prediction of the Clinical Dose-Response Relationship Using Intracellular Pharmacodynamic Modeling (PDi)

Methods Mol Biol. 2021:2296:393-408. doi: 10.1007/978-1-0716-1358-0_23.

Abstract

The human disease tuberculosis (TB) is the leading cause of death from a single infectious agent. A quarter of the world's population is estimated to be latently infected. Drug development and screening is slow and costly. We have developed a physiologically relevant assay to screen drugs against TB when inside immune cells. This chapter will describe a newly developed preclinical drug screening assay for TB, using high-content imaging and pharmacokinetic/pharmacodynamic modeling.

Keywords: Antibiotics; Drug screening; Mycobacteria; Pharmacokinetic and pharmacodynamic drug Modeling; Tuberculosis.

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Bacterial Proteins / metabolism
  • Dose-Response Relationship, Drug
  • Drug Development / methods
  • Humans
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / metabolism
  • THP-1 Cells
  • Tuberculosis / drug therapy*

Substances

  • Antitubercular Agents
  • Bacterial Proteins