Observational studyThe Journal of antimicrobial chemotherapy2022
Pharmacokinetics of standard versus high-dose isoniazid for treatment of multidrug-resistant tuberculosis.
Observational study in The Journal of antimicrobial chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Population pharmacokinetics of pyrazinamide and isoniazid in plasma and cerebrospinal fluid from South African adults with tuberculous meningitis.Antimicrobial agents and chemotherapy · 2025Trial
- The impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs.The Journal of antimicrobial chemotherapy · 2024Article
- Pharmacokinetics and pharmacodynamics of high-dose isoniazid for the treatment of rifampicin- or multidrug-resistant tuberculosis in Indonesia.The Journal of antimicrobial chemotherapy · 2024Observational
- Fabrication of nanocrystal forms of ᴅ-cycloserine and their application for transdermal and enteric drug delivery systems.Beilstein journal of nanotechnology · 2024Article
- Application of a physiologically based pharmacokinetic model to predict isoniazid disposition during pregnancy.Clinical and translational science · 2023Article
Corrections and comments
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Authors and funding
18 authors at 10 institutions in 2 countries.
Funding
Abstract
backgroundThe WHO-endorsed shorter-course regimen for MDR-TB includes high-dose isoniazid. The pharmacokinetics of high-dose isoniazid within MDR-TB regimens has not been well described.
objectivesTo characterize isoniazid pharmacokinetics at 5-15 mg/kg as monotherapy or as part of the MDR-TB treatment regimen.
methodsWe used non-linear mixed-effects modelling to evaluate the combined data from INHindsight, a 7 day early bactericidal activity study with isoniazid monotherapy, and PODRtb, an observational study of patients on MDR-TB treatment including terizidone, pyrazinamide, moxifloxacin, kanamycin, ethionamide and/or isoniazid.
resultsA total of 58 and 103 participants from the INHindsight and PODRtb studies, respectively, were included in the analysis. A two-compartment model with hepatic elimination best described the data. N-acetyltransferase 2 (NAT2) genotype caused multi-modal clearance, and saturable first-pass was observed beyond 10 mg/kg dosing. Saturable isoniazid kinetics predicted an increased exposure of approximately 50% beyond linearity at 20 mg/kg dosing. Participants treated with the MDR-TB regimen had a 65.6% lower AUC compared with participants on monotherapy. Ethionamide co-administration was associated with a 29% increase in isoniazid AUC.
conclusionsMarkedly lower isoniazid exposures were observed in participants on combination MDR-TB treatment compared with monotherapy. Isoniazid displays saturable kinetics at doses >10 mg/kg. The safety implications of these phenomena remain unclear.
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