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Tuberculosis drugs' distribution and emergence of resistance in patient's lung lesions: A mechanistic model and tool for regimen and dose optimization.

08:00 EDT 2nd April 2019 | BioPortfolio

Summary of "Tuberculosis drugs' distribution and emergence of resistance in patient's lung lesions: A mechanistic model and tool for regimen and dose optimization."

The sites of mycobacterial infection in the lungs of tuberculosis (TB) patients have complex structures and poor vascularization, which obstructs drug distribution to these hard-to-reach and hard-to-treat disease sites, further leading to suboptimal drug concentrations, resulting in compromised TB treatment response and resistance development. Quantifying lesion-specific drug uptake and pharmacokinetics (PKs) in TB patients is necessary to optimize treatment regimens at all infection sites, to identify patients at risk, to improve existing regimens, and to advance development of novel regimens. Using drug-level data in plasma and from 9 distinct pulmonary lesion types (vascular, avascular, and mixed) obtained from 15 hard-to-treat TB patients who failed TB treatments and therefore underwent lung resection surgery, we quantified the distribution and the penetration of 7 major TB drugs at these sites, and we provide novel tools for treatment optimization.

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Journal Details

This article was published in the following journal.

Name: PLoS medicine
ISSN: 1549-1676
Pages: e1002773

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Medical and Biotech [MESH] Definitions

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RESPIRATORY MUSCLE contraction during INHALATION. The work is accomplished in three phases: LUNG COMPLIANCE work, that required to expand the LUNGS against its elastic forces; tissue resistance work, that required to overcome the viscosity of the lung and chest wall structures; and AIRWAY RESISTANCE work, that required to overcome airway resistance during the movement of air into the lungs. Work of breathing does not refer to expiration, which is entirely a passive process caused by elastic recoil of the lung and chest cage. (Guyton, Textbook of Medical Physiology, 8th ed, p406)

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Division of the tissues attaching the lung to the wall of the chest cavity, to permit collapse of the lung. It was formerly used to treat tuberculosis. (Dorland, 28th ed)

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