Isoniazid and rifampicin exposure during treatment in drug-susceptible TB

O W Akkerman*, R D C Dijkwel, H A M Kerstjens, T S van der Werf, S Srivastava, M G G Sturkenboom, M S Bolhuis

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

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BACKGROUND: 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.

METHODS: 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).

RESULTS: 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.

CONCLUSION: 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.

Originele taal-2English
Pagina's (van-tot)772-777
Aantal pagina's6
TijdschriftThe international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Volume27
Nummer van het tijdschrift10
DOI's
StatusPublished - 1-okt.-2023

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