Isoniazid and rifampicin exposure during treatment in drug-susceptible TB

<bold>BACKGROUND:</bold> Observational real-world studies on therapeutic drug monitoring (TDM) in relation to pharmacokinetic (PK) target values are lacking. This study aims to describe the PK of rifampicin (RIF) and isoniazid (INH) in a real-world setting of patients with drug-susceptible TB in relation to frequently used threshold values.<bold>METHODS:</bold> A total of 116 patients with TB using standard doses of RIF and INH and who had TDM as part of clinical care were included. Maximum plasma concentration (C-max) and 24 h area under the concentration time curve (AUC(24)) at standard and revised doses were described in relation to the threshold values (C-max >= 8 mg/L for RIF and >= 3 mg/L for INH).<bold>RESULTS:</bold> For RIF (100 patients), median C-max and median AUC(24) were respectively 7.9 mg/L (IQR 6.0-11.0) and 35.8 mg*h/L (IQR 27.4-57.3) at the first TDM measurement after a standard dose of 600 mg. For INH (90 patients), median C-max and median AUC(24) were respectively 2.9 mg/L (IQR 1.3-2.5) and 12.5 mg*h/L (IQR 8.7-18.9) at the first TDM after a standard dose 300 mg. Overall, more than 50% of study participants had drug exposure below threshold values at the first TDM.<bold>CONCLUSION:</bold> Our study shows that the measured C-max values for both RIF and INH were frequently below the pre-specified targets, emphasising the need for better justification of drug exposure targets. These TDM results highlight the need for validating PK targets of anti-TB drugs associated with clinically relevant outcomes.