Pretomanid: From Development to the Implementation of Short-Term Tuberculosis Chemotherapy Regimens: A Literature Review
Abstract
The objective: to analyze preclinical and clinical studies on the mechanisms of action, efficacy and safety of the antituberculosis drug pretomanid (PA-824/ F₄₂₀- Pa). Materials and methods: This review presents the results of 48 publications, including clinical trials evaluating the activity and efficacy of pretomanid (PA-824/ F₄₂₀- Pa) – a member of the nitroimidazopyran class developed for treatment of tuberculosis (TB). This drug is effective against both replicating and persistent Mycobacterium tuberculosis (Mtb), particularly under hypoxic conditions. Preclinical studies demonstrated high activity of Pa against both drug-susceptible and drug-resistant M. tuberculosis. Pa became a key component of the short-term, all-oral regimens, such as BPaL (bedaquiline, pretomanid, and linezolid), for treatment of multidrug-resistant and pre-extensively drug-resistant TB Phase III clinical trials (Nix-TB, ZeNix-TB, and TB-PRACTECAL) confirmed that these regimens achieve cure in just 6 months with a favorable safety profile. Consequently, the duration of effective treatment for drug-resistant TB becomes comparable to that for drug-susceptible TB.
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