Abstract
Tuberculosis (TB) is a globally prevalent infectious disease, particularly in
developing countries. Previous studies have demonstrated pharmacokinetic variability
in anti-tuberculosis drug concentrations due to various factors, including genetic
diversity. However, population pharmacokinetic data of anti-tuberculosis drugs in Thai
individuals are currently lacking. In this study, we reported the population
pharmacokinetics of four first-line anti-tuberculosis drugs—isoniazid, rifampicin,
ethambutol, and pyrazinamide—based on full population pharmacokinetic data from
59 adult Thai TB patients. The findings revealed that NAT2 phenotype influenced the
clearance (CL) of isoniazid, while HIV status affected its bioavailability. For rifampicin,
lean body weight was associated with the absorption rate constant, and HIV status
impacted its clearance. Additionally, renal function was found to influence the
pharmacokinetic variability of ethambutol, while lean body weight affected both the
absorption rate constant and volume of distribution of pyrazinamide. This study also
reported the minimum inhibitory concentrations (MICs) of both first-line and secondline anti-tuberculosis drugs. In summary, therapeutic drug monitoring of antituberculosis drugs, in combination with pharmacogenetic testing—particularly for
NAT2—and clinical parameters such as HIV status, lean body weight, and renal
function, can be applied clinically to support individualized dosing and optimize
treatment outcomes.
