Ethambutol Partitioning in Tuberculous Pulmonary Lesions Explains Its Clinical Efficacy.

ABSTRACT: Clinical trials and practice have shown that ethambutol is an important component of the first-line tuberculosis (TB) regime. This contrasts the drug's rather modest potency and lack of activity against nongrowing persister mycobacteria. The standard plasma-based pharmacokinetic-pharmacodynamic profile of ethambutol suggests that the drug may be of limited clinical value. Here, we hypothesized that this apparent contradiction may be explained by favorable penetration of the drug into TB lesions. First, we utilized novel in vitro lesion pharmacokinetic assays and predicted good penetration of the drug into lesions. We then employed mass spectrometry imaging and laser capture microdissection coupled to liquid chromatography and tandem mass spectrometry (LCM and LC/MS-MS, respectively) to sho

SUBMITTER: Zimmerman M 

PROVIDER: S-EPMC5571334 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature