English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

The Multistate Tuberculosis Pharmacometric (MTP) model, a pharmacokinetic-pharmacodynamic disease model, has been used to describe the effects of rifampicin on Mycobacterium tuberculosis (M. tuberculosis) in vitro. The aim of this work was to investigate if the MTP model could be used to describe the rifampicin treatment response in an acute tuberculosis mouse model. Sixty C57BL/6 mice were intratracheally infected with M. tuberculosis H37Rv strain on Day 0. Fifteen mice received no treatment and were sacrificed on Days 1, 9 and 18 (5 each day). Twenty-five mice received oral rifampicin (1, 3, 9, 26 or 98 mg·kg -1 ·day -1 ; Days 1-8; 5 each dose level) and were sacrificed on Day 9. Twenty mice received oral rifampicin (30 mg·kg -1 ·day -1 ; up to 8 days) and were sacrificed on Days 2, 3, 4 and 9 (5 each day). The MTP model was linked to a rifampicin population pharmacokinetic model to describe the change in colony forming units (CFU) in the lungs over time. The transfer rates between the different bacterial states were fixed to estimates from in vitro data. The MTP model described well the change in CFU over time after different exposure levels of rifampicin in an acute tuberculosis mouse model. Rifampicin significantly inhibited the growth of fast-multiplying bacteria and stimulated the death of fast- and slow-multiplying bacteria. The data did not support an effect of rifampicin on non-multiplying bacteria possibly due to the short duration of the study. The pharmacometric modelling framework using the MTP model can be used to perform investigations and predictions of the efficacy of anti-tubercular drugs against different bacterial states.

journal of pharmacokinetics and pharmacodynamics

The multistate tuberculosis pharmacometric model: a semi-mechanistic pharmacokinetic-pharmacodynamic model for studying drug effects in an acute tuberculosis mouse model