Pharmacokinetics of Anti-Tuberculosis Drug Treatments

The pharmacokinetics of anti-tuberculosis (TB) drugs encompasses the processes of absorption, distribution, metabolism and excretion that determine drug concentrations at sites of infection. First-line agents such as isoniazid, rifampicin, ethambutol and pyrazinamide exhibit distinct profiles of absorption and tissue penetration, influenced by factors including gastric pH, concurrent food intake and genetic polymorphisms of metabolising enzymes. Second-line compounds, notably cycloserine and fluoroquinolones, pose additional challenges in dosing optimisation to balance efficacy against neuropsychiatric and other adverse effects. Population pharmacokinetic modelling has become instrumental in defining dosing regimens tailored to individual patient characteristics, such as weight, age, renal function and HIV co-infection. Therapeutic drug monitoring is increasingly advocated in multidrug-resistant TB (MDR-TB) to ensure adequate exposure, especially in settings where interindividual variability may compromise treatment outcomes. Enhanced understanding of tissue distribution, including penetration into pulmonary lesions and intracellular compartments, is driving development of novel formulations and dosing strategies. Ultimately, integration of pharmacokinetic insights with pharmacodynamic targets—such as time above minimum inhibitory concentration and area under the concentration–time curve to MIC ratio—is underpinning efforts to shorten treatment duration and curb the global burden of TB.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Pharmacokinetics of Anti-Tuberculosis Drug Treatments publication trend

The graph below shows the total number of articles in pharmacokinetics of anti-tuberculosis drug treatments across all publications each year (not limited to Nature Index journals).

Technical terms

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

Bioavailability: Fraction of administered dose reaching systemic circulation in active form.

Minimum inhibitory concentration (MIC): Lowest drug concentration that inhibits visible growth of Mycobacterium tuberculosis.

One-compartment model: Simplified pharmacokinetic representation assuming uniform drug distribution throughout the body.

Population pharmacokinetics: Statistical modelling of drug concentration data across individuals to identify sources of variability and optimise dosing.

References

1. Cycloserine Population Pharmacokinetics and Pharmacodynamics in Patients with Tuberculosis. Antimicrobial Agents and Chemotherapy (2019).
2. Effect of tablet crushing on drug exposure in the treatment of multidrug-resistant tuberculosis. The International Journal of Tuberculosis and Lung Disease (2019).