Therapeutic Drug Monitoring in Tuberculosis Treatment

Therapeutic drug monitoring (TDM) has emerged as a vital strategy to optimise antitubercular therapy by measuring drug concentrations in biological fluids and adjusting doses to achieve predefined therapeutic targets. Variability in absorption, metabolism and clearance of first-line agents such as isoniazid and rifampicin can result in subtherapeutic exposures, delayed sputum conversion and the emergence of drug resistance. Pharmacogenomic differences, notably polymorphisms in N-acetyltransferase 2 (NAT2), further influence isoniazid acetylation rates, while comorbidities such as HIV, diabetes and malnutrition can alter pharmacokinetic parameters. Advances in analytical methods, including high-performance liquid chromatography and mass spectrometry, allow for rapid, precise quantification of plasma levels, facilitating dose optimisation. Physiologically based pharmacokinetic (PBPK) modelling and population pharmacokinetic analyses are increasingly integrated with TDM to predict individualised dosing regimens and support real-time decision making. By targeting key pharmacokinetic/pharmacodynamic indices—such as the ratio of the area under the concentration–time curve (AUC) to the minimum inhibitory concentration (MIC)—TDM aims to maximise bacterial kill while minimising toxicity. In high-burden settings, implementation of TDM is challenged by resource constraints, yet its potential to shorten treatment duration, reduce adverse events and curb transmission underscores its global importance in tuberculosis control.

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Therapeutic Drug Monitoring in Tuberculosis Treatment publication trend

The graph below shows the total number of articles in therapeutic drug monitoring in tuberculosis treatment across all publications each year (not limited to Nature Index journals).

Technical terms

Therapeutic drug monitoring (TDM): Measurement of drug concentrations in bodily fluids to guide individual dosing and optimise efficacy.

Pharmacokinetics: Study of the absorption, distribution, metabolism and excretion of drugs in the body.

Pharmacogenomics: Investigation of genetic factors that influence an individual’s response to medications.

Acetylator status: Classification of individuals as slow, intermediate or rapid metabolizers of isoniazid based on NAT2 gene polymorphisms.

Area under the concentration–time curve (AUC): Integral of drug concentration over time, reflecting overall exposure.

Minimum inhibitory concentration (MIC): Lowest concentration of an antimicrobial that prevents visible growth of a microorganism.

References

1. A Nanopore Sequencing-based Pharmacogenomic Panel to Personalize Tuberculosis Drug Dosing. American Journal of Respiratory and Critical Care Medicine (2024).
2. Evaluating pediatric tuberculosis dosing guidelines: A model-based individual data pooled analysis. PLOS Medicine (2023).
3. Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis. Journal of Antimicrobial Chemotherapy (2018).