The need for systematic therapeutic drug monitoring of isoniazid in tuberculosis, a real-world study.

OBJECTIVES: Isoniazid is a primary first-line antituberculosis agent, exhibiting concentration-dependent bactericidal effect while also posing a risk of hepatotoxicity. Therapeutic drug monitoring (TDM) could optimize exposure but remains underused. This study aimed to assess isoniazid pharmacokinetic variability in real-world settings and the proportion of patients achieving therapeutic concentrations. METHODS: We conducted a retrospective, single-center study of adult tuberculosis patients receiving standard first-line therapy (isoniazid, rifampicin, pyrazinamide, ethambutol). Patients underwent fasted-state isoniazid monitoring via a 4-point limited-sampling protocol. We calculated AUC₀₋₂₄ₕ and acetylation status (rapid: half-life 21.8 h·mg/L). Nearly one-third had Cmax within the expected range but AUC₀₋₂₄ₕ above the safety limit. CONCLUSION: Real-world data reveal substantial isoniazid exposure variability, with frequent deviations from target AUC₀₋₂₄ₕ. These findings advocate for systematic TDM and individualized dosing, prioritizing AUC₀₋₂₄ₕ as a key monitoring parameter.