The Role of Efflux Pumps in Tuberculosis Treatment and Their Promise as a Target in Drug Development: Unraveling the Black Box
| Autor: | Jurriaan E. M. de Steenwinkel, David M. Burger, Jan B. Koenderink, Reinout van Crevel, Frans G. M. Russel, Gerjo J. de Knegt, Rob E. Aarnoutse, Lindsey H.M. te Brake, Teunis J. P. van Dam |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
drug-drug interactions Tuberculosis efflux pumps 030106 microbiology Antitubercular Agents lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ATP-binding cassette transporter Drug resistance Biology Pharmacology Toxicology Tuberculous meningitis Mycobacterium tuberculosis resistance 03 medical and health sciences Drug Development Pharmacokinetics medicine Animals Humans tolerance Membrane Transport Proteins biology.organism_classification medicine.disease Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] 030104 developmental biology Drug development tuberculosis ABC transporters tuberculous meningitis Immunology Efflux |
| Zdroj: | Annual review of pharmacology and toxicology, 58, pp. 271-291 Annual review of pharmacology and toxicology, 58, 271-291 Annual Review of Pharmacology and Toxicology. Annual Reviews Inc. |
| ISSN: | 0362-1642 |
| Popis: | 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. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 58 is January 6, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates. |
| Databáze: | OpenAIRE |
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