Isoniazid and rifampicin exposure during treatment in drug-susceptible TB.

Autor: Akkerman OW; Department of Pulmonary Diseases and Tuberculosis, University Medical Center Groningen, University of Groningen, Groningen, Tuberculosis Center Beatrixoord, University of Groningen, University Medical Center Groningen, Haren., Dijkwel RDC; Departments of Clinical Pharmacy and Pharmacology, and., Kerstjens HAM; Department of Pulmonary Diseases and Tuberculosis, University Medical Center Groningen, University of Groningen, Groningen., van der Werf TS; Department of Pulmonary Diseases and Tuberculosis, University Medical Center Groningen, University of Groningen, Groningen, Departments of Internal Medicine and Infectiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Srivastava S; Department of Medicine, The University of Texas Health Science Center at Tyler, Tyler, TX, USA, Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX, USA, Department of Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX, USA., Sturkenboom MGG; Departments of Clinical Pharmacy and Pharmacology, and., Bolhuis MS; Departments of Clinical Pharmacy and Pharmacology, and.
Jazyk: angličtina
Zdroj: The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease [Int J Tuberc Lung Dis] 2023 Oct 01; Vol. 27 (10), pp. 772-777.
DOI: 10.5588/ijtld.22.0698
Abstrakt: 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.
Databáze: MEDLINE
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