Pharmacokinetics of Bedaquiline and Linezolid in TB patients.

Author: Nikoloz Shurgaia
Keywords: Tuberculosis, Pharmacokinetics, Bedaquiline, Linezolid, Pretomanid, Liquid Chromatography, Mass Spectrometry
Annotation:

Each year more than 1.5 million people die from Tuberculosis. Up to 15% of those deaths are due to RR/MDR-TB. BPaL/BPaLM regimens developed by TB Alliance and consisting of Bedaquiline, Pretomanid, Linezolid and Moxifloxacin are a modern approach to treat RR/MDR TB patients. Of those 4, Linezolid has been associated with numerous Adverse Events (AEs) and, due to its narrow therapeutic range and high toxicity, has a high incidence of causing such AEs. In the year 2023 the Ministry of Health of Georgia, based on WHO recommendations, released a new TB Treatment Guideline, programmatically approving BPaL 6-9 and BPaLM 6-month treatment regimens for patients with RR/MDR. Even though there are several published studies worldwide that specifically examine Linezolid Cmin and measure interpatient variability, to date, only one such study has been published in a Georgian setting. For patients receiving Linezolid treatment, therapeutic drug monitoring (TDM) is the solution of choice in some clinics, particularly in developed countries. However, in the Georgian setting, the utility of a programmatic approach to TDM has yet to be fully justified. To work towards achieving this future goal, this study proposes to investigate the interpatient variability of Linezolid Cmin. The AIMS AIM 1 is to develop a simultaneous LC-MS/MS quantitative analysis method for BDQ, PA and LZD. AIM 2 is to quantify the LZD Cmin serum concentrations. The proposed study will shed more light on the necessity of individualized drug concentration monitoring for Linezolid in patients undergoing treatment with the newly introduced BPaL/BPaLM regimens. This, in turn, will supply researchers, clinicians and decision-makers with more data to evaluate the overall feasibility of implementing a programmatic approach for TDM of Linezolid in Georgia.

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ბედაქილინისა და ლინეზოლიდის ფარმაკოკინეტიკის კვლევა ტუბერკულოზით დაავადებულ პაციენტებში. [ka]