Tuberculosis is the most fatal bacterial infectious disease worldwide with about 1.5 million deaths annually. Infections caused by highly resistant Mycobacterium tuberculosis strains (MDR-, XDR-, XXDR-TB) cause particular problems. With BTZ-043, a new substance with outstanding efficacy against resistant tuberculosis pathogens was found at the Leibniz Institute for Natural Product Research - Hans Knöll Institute - which has a completely new mechanism of action.
An essential regulatory component of preclinical development is the quantitative detection, identification and toxicological characterisation of all metabolites relevant to humans. This component of drug development is to be investigated within the framework of BTZ-Met-ID project. The complete, quantitative determination of all metabolites is carried out by administration of radioactively labelled active substance, which must be specially developed for use in humans. The subsequent quantification and balancing of the metabolites in humans is finally performed by analysis of body fluids and excretions from healthy volunteers. The comparison with animal experiments must ensure that all metabolites relevant in humans are toxicologically harmless. At the end of the project, a complete picture of the metabolism of BTZ-043 in humans and animals will be available. Together with results from toxicology, this allows a sufficiently reliable risk assessment for the use of BTZ-043 in humans.
- Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (Coordinator)
- Hospital of the University of Munich
- HAPILA Ltd.