A Dose-Finding Study to Guide Use of Verapamil as an Adjunctive Therapy in Tuberculosis.

ABSTRACT: Induction of mycobacterial efflux pumps is a cause of Mycobacterium tuberculosis (Mtb) drug tolerance, a barrier to shortening antitubercular treatment. Verapamil inhibits Mtb efflux pumps that mediate tolerance to rifampin, a cornerstone of tuberculosis (TB) treatment. Verapamil's mycobacterial efflux pump inhibition also limits Mtb growth in macrophages in the absence of antibiotic treatment. These findings suggest that verapamil could be used as an adjunctive therapy for TB treatment shortening. However, verapamil is rapidly and substantially metabolized when co-administered with rifampin. We determined in a dose-escalation clinical trial of persons with pulmonary TB that rifampin-induced clearance of verapamil can be countered without toxicity by the administration of larger than usual

SUBMITTER: Padmapriyadarsini C 

PROVIDER: S-EPMC7615557 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature