Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and Monte Carlo simulation.

ABSTRACT:

Objectives

The oxazolidinone linezolid is an effective component of drug-resistant TB treatment, but its use is limited by toxicity and the optimum dose is uncertain. Current strategies are not informed by clinical pharmacokinetic (PK)/pharmacodynamic (PD) data; we aimed to address this gap.

Methods

We defined linezolid PK/PD targets for efficacy (fAUC0-24:MIC >119 mg/L/h) and safety (fCmin <1.38 mg/L). We extracted individual-level linezolid PK data from existing studies on TB patients and performed meta-analysis, producing summary estimates of fAUC0-24 and fCmin for published doses. Combining these with a published MIC distribution, we performed Monte Carlo simulations of target attainment.

Results

The efficacy target was attained in all simulated individuals at 300

SUBMITTER: Millard J 

PROVIDER: S-EPMC6005026 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature