Noninvasive 11C-rifampin positron emission tomography reveals drug biodistribution in tuberculous meningitis.

ABSTRACT: Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB), and key TB antimicrobials, including rifampin, have restricted brain penetration. A lack of reliable data on intralesional drug biodistribution in infected tissues has limited pharmacokinetic (PK) modeling efforts to optimize TBM treatments. Current methods to measure intralesional drug distribution rely on tissue resection, which is difficult in humans and generally limited to a single time point even in animals. In this study, we developed a multidrug treatment model in rabbits with experimentally induced TBM and performed serial noninvasive dynamic 11C-rifampin positron emission tomography (PET) over 6 weeks. Area under the curve brain/plasma ratios were calculated using PET and correlated with postmortem mass spec

SUBMITTER: Tucker EW 

PROVIDER: S-EPMC6360528 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature