ArticleBritish journal of clinical pharmacology2011
Variability in the population pharmacokinetics of isoniazid in South African tuberculosis patients.
Article in British journal of clinical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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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
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- A systematic review and meta-analysis of first-line tuberculosis drug concentrations and treatment outcomes.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2020Pooled it
- High-Dose Isoniazid Lacks EARLY Bactericidal Activity against Isoniazid-resistant Tuberculosis Mediated by katG Mutations: A Randomized Phase II Clinical Trial.American journal of respiratory and critical care medicine · 2024Trial
- High Isoniazid Exposures When Administered with Rifapentine Once Weekly for Latent Tuberculosis in Individuals with Human Immunodeficiency Virus.Antimicrobial agents and chemotherapy · 2023Trial
- Pharmacokinetics and Pharmacodynamics of Intensive Antituberculosis Treatment of Tuberculous Meningitis.Clinical pharmacology and therapeutics · 2020Trial
- Effect of efavirenz-based antiretroviral therapy and high-dose rifampicin on the pharmacokinetics of isoniazid and acetyl-isoniazid.The Journal of antimicrobial chemotherapy · 2019Trial
- Pharmacokinetics of Antituberculosis Drugs in HIV-Positive and HIV-Negative Adults in Malawi.Antimicrobial agents and chemotherapy · 2015Trial
- Impact of nonlinear interactions of pharmacokinetics and MICs on sputum bacillary kill rates as a marker of sterilizing effect in tuberculosis.Antimicrobial agents and chemotherapy · 2015Trial
- Pharmacokinetics of rifampin and isoniazid in tuberculosis-HIV-coinfected patients receiving nevirapine- or efavirenz-based antiretroviral treatment.Antimicrobial agents and chemotherapy · 2014Trial
- Isoniazid pharmacokinetics, pharmacodynamics, and dosing in South African infants.Therapeutic drug monitoring · 2012Trial
- Pharmacokinetics of first-line tuberculosis drugs rifampin, isoniazid, ethambutol, and pyrazinamide during pregnancy and postpartum with and without efavirenz-based antiretroviral treatment: IMPAACT P1026s study.Antimicrobial agents and chemotherapy · 2025Article
- Characterization of the complex TB pharmacogenomic landscape in Africa using bioinformatic tools.Briefings in bioinformatics · 2025Article
- Timing of recurrence after treatment of pulmonary TB.IJTLD open · 2024Article
- The impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs.The Journal of antimicrobial chemotherapy · 2024Article
- Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB.IJTLD open · 2024Article
- Model-Informed Precision Dosing of Isoniazid: Parametric Population Pharmacokinetics Model Repository.Drug design, development and therapy · 2024Article
- Risk adjustment model for tuberculosis compared to non-tuberculosis mycobacterium or latent tuberculosis infection: Center for Personalized Precision Medicine of Tuberculosis (cPMTb) cohort database.BMC pulmonary medicine · 2023Article
- Correlation of N-acetyltransferase 2 genotype and acetylation status with plasma isoniazid concentration and its metabolic ratio in ethiopian tuberculosis patients.Scientific reports · 2023Article
- Clinical impact of plasma concentrations of first-line antituberculosis drugs.South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde · 2023Article
- Isoniazid pharmacokinetics/pharmacodynamics as monotherapy and in combination regimen in the hollow fiber system model of Mycobacterium kansasii.Tuberculosis (Edinburgh, Scotland) · 2023Article
- Quantitative Analysis of Isoniazid and Its Four Primary Metabolites in Plasma of Tuberculosis Patients Using LC-MS/MS.Molecules (Basel, Switzerland) · 2022Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThis study was designed to characterize the population pharmacokinetics of isoniazid in South African pulmonary tuberculosis patients.
methodsConcentration-time measurements obtained from 235 patients receiving oral doses of isoniazid as part of routine tuberculosis chemotherapy in two clinical studies were pooled and subjected to nonlinear mixed-effects analysis.
resultsA two-compartmental model, including first-order absorption and elimination with allometric scaling, was found to describe the observed dose-exposure relationship for oral isoniazid adequately. A mixture model was used to characterize dual rates of isoniazid elimination. Estimates of apparent clearance in slow and fast eliminators were 9.70 and 21.6 l h(-1) , respectively. The proportion of fast eliminators in the population was estimated to be 13.2%. Central volume of distribution was estimated to be 10% smaller in female patients and clearance was found to be 17% lower in patients with HIV. Variability in absorption rate (90%) was completely interoccasional in nature, whereas in relative bioavailability, interoccasional variability (8.4%) was lower than interindividual variability (26%). Oral doses, given once daily according to dosing policies at the time, were sufficient to reach therapeutic concentrations in the majority of the studied population, regardless of eliminator phenotype. Simulations suggested that current treatment guidelines (5 mg kg(-1) ) may be suboptimal in fast eliminators with low body weight.
conclusionsA population pharmacokinetic model was developed to characterize the highly variable pharmacokinetics of isoniazid in a South African pulmonary tuberculosis patient population. Current treatment guidelines may lead to underexposure in rapid isoniazid eliminators.
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