Measuring anti-TB drug concentrations in hair: un<i>lock</i>ing the door to cumulative drug exposure and treatment outcome

Alffenaar, J. W. C.; Marais, Ben J; Heysell, Scott K

doi:10.5588/ijtld.20.0797

Cited by 1 publication

(2 citation statements)

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“…Population pharmacokinetic modeling and pharmacokinetic-pharmacodynamic studies could help predict the most appropriate individual dose, and model-informed precision dosing could also be utilized in predicting sampling schedules and exposures in alternative matrices [ 101 ]. Variable factors need to be taken into consideration to provide high-level evidence for TDM and these include volume and hematocrit effects for DBS [ 9 ]; pH, fraction of drug eliminated renally, hydration, renal function for urine [ 98 ]; salivary flow and pH [ 17 ]; and understanding relevant serum exposures from hair concentrations [ 23 ]. Having validated analytical methods for plasma and or serum and the alternative matrix, and the ability to calculate plasma-matrix ratios from AUC values form important components of a rigorous pharmacokinetic study design [ 17 ].…”

Section: Discussionmentioning

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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