The Role of Efflux Pumps in Tuberculosis Treatment and Their Promise as a Target in Drug Development: Unraveling the Black Box
until further notice
SourceAnnual review of pharmacology and toxicology, 58, (2018), pp. 271-291
Article / Letter to editor
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IMM - Institute for Molecules and Materials
Annual review of pharmacology and toxicology
SubjectRadboudumc 11: Renal disorders RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 4: lnfectious Diseases and Global Health RIHS: Radboud Institute for Health Sciences; Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences
Insight into drug transport mechanisms is highly relevant to the efficacious treatment of tuberculosis (TB). Major problems in TB treatment are related to the transport of antituberculosis (anti-TB) drugs across human and mycobacterial membranes, affecting the concentrations of these drugs systemically and locally. Firstly, transporters located in the intestines, liver, and kidneys all determine the pharmacokinetics and pharmacodynamics of anti-TB drugs, with a high risk of drug-drug interactions in the setting of concurrent use of antimycobacterial, antiretroviral, and antidiabetic agents. Secondly, human efflux transporters limit the penetration of anti-TB drugs into the brain and cerebrospinal fluid, which is especially important in the treatment of TB meningitis. Finally, efflux transporters located in the macrophage and Mycobacterium tuberculosis cell membranes play a pivotal role in the emergence of phenotypic tolerance and drug resistance, respectively. We review the role of efflux transporters in TB drug disposition and evaluate the promise of efflux pump inhibition from a novel holistic perspective.
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