Correlation of Linezolid Hair Concentrations with Plasma Exposure in Patients with Drug-Resistant Tuberculosis

Wasserman, Sean; Huo, Stella; Ky, Karina; Malig, Ysabella Noelle Amora; Esmail, Ali; Dheda, Keertan; Bacchetti, Peter; Gerona, Roy; Maartens, Gary; Gandhi, Monica; Metcalfe, John

doi:10.1128/aac.02145-19

Cited by 2 publications

(3 citation statements)

References 6 publications

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“…Liquid chromatography-tandem mass spectrometry was used in all studies to quantify the various anti-TB drugs from hair (Table 5 ). Only two [ 22 , 84 ] of the 13 studies performed comparative pharmacokinetic studies in plasma as well as hair samples, and simple scatter plots were used to demonstrate correlations. All studies were assessed for the risk of bias and two studies had a moderate risk of bias because of the selection of participants as one study [ 85 ] had 98% female participants and the other [ 22 ] enrolled all male participants.…”

Section: Resultsmentioning

confidence: 99%

“…Only two [22,84] of the 13 studies performed comparative pharmacokinetic studies in plasma as well as hair samples, and simple scatter plots were used to demonstrate correlations. All studies were assessed for the risk of bias and two studies had a moderate risk of bias because of the selection of participants as one study [85] had 98% female participants and the other [22] enrolled all male participants. Other studies [21,[82][83][84][86][87][88][89][90][91][92] had a low overall risk of bias.…”

Section: Hairmentioning

confidence: 99%

“…However, cumulative exposure throughout the treatment period is not captured by these metrics. Measuring drug concentrations in hair, especially of drugs with short half-lives such as isoniazid [ 21 ] and linezolid [ 22 ], may be more representative of long-term pharmacokinetic exposure that is dependent upon the four parameters of absorption, distribution, metabolism, and elimination, but also patterns of adherence to prescribed medications, a potentially important feature for anti-TB care where treatment courses are long [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Alternative Methods for Therapeutic Drug Monitoring and Dose Adjustment of Tuberculosis Treatment in Clinical Settings: A Systematic Review

et al. 2023

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Background and Objective Quantifying exposure to drugs for personalized dose adjustment is of critical importance in patients with tuberculosis who may be at risk of treatment failure or toxicity due to individual variability in pharmacokinetics. Traditionally, serum or plasma samples have been used for drug monitoring, which only poses collection and logistical challenges in high-tuberculosis burden/low-resourced areas. Less invasive and lower cost tests using alternative biomatrices other than serum or plasma may improve the feasibility of therapeutic drug monitoring. Methods A systematic review was conducted to include studies reporting anti-tuberculosis drug concentration measurements in dried blood spots, urine, saliva, and hair. Reports were screened to include study design, population, analytical methods, relevant pharmacokinetic parameters, and risk of bias. Results A total of 75 reports encompassing all four biomatrices were included. Dried blood spots reduced the sample volume requirement and cut shipping costs whereas simpler laboratory methods to test the presence of drug in urine can allow point-of-care testing in high-burden settings. Minimal pre-processing requirements with saliva samples may further increase acceptability for laboratory staff. Multi-analyte panels have been tested in hair with the capacity to test a wide range of drugs and some of their metabolites. Conclusions Reported data were mostly from small-scale studies and alternative biomatrices need to be qualified in large and diverse populations for the demonstration of feasibility in operational settings. High-quality interventional studies will improve the uptake of alternative biomatrices in guidelines and accelerate implementation in programmatic tuberculosis treatment.

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