P-glycoprotein inhibitors as an adjunct therapy for TB.

Drug Discov Today

Department of Biological Sciences (Pharmacology and Toxicology), National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India. Electronic address:

Published: September 2024

The primary challenge in TB treatment is the emergence of multidrug-resistant TB (MDR-TB). One of the major factors responsible for MDR is the upregulation of efflux pumps. Permeation-glycoprotein (P-gp), an efflux pump, hinders the bioavailability of the administered drugs inside the infected cells. Simultaneously, angiogenesis, the formation of new blood vessels, contributes to drug delivery complexities. TB infection triggers a cascade of events that upregulates the expression of angiogenic factors and P-gp. The combined action of P-gp and angiogenesis foster the emergence of MDR-TB. Understanding these mechanisms is pivotal for developing targeted interventions to overcome MDR in TB. P-gp inhibitors, such as verapamil, and anti-angiogenic drugs, including bevacizumab, have shown improvement in TB drug delivery to granuloma. In this review, we discuss the potential of P-gp inhibitors as an adjunct therapy to shorten TB treatment.

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Source
http://dx.doi.org/10.1016/j.drudis.2024.104108DOI Listing

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