ArticleAntimicrobial agents and chemotherapy2007
Isoniazid bactericidal activity and resistance emergence: integrating pharmacodynamics and pharmacogenomics to predict efficacy in different ethnic populations.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 6 of them syntheses 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
93 citing papers in PubMed, 6 syntheses or guidelines pooled it, 161 citations in OpenAlex.
- Influence of N-acetyltransferase 2 (NAT2) genotype/single nucleotide polymorphisms on clearance of isoniazid in tuberculosis patients: a systematic review of population pharmacokinetic models.European journal of clinical pharmacology · 2022Pooled it
- The role of hepatitis B infection in anti-tuberculosis drug-induced liver injury: a meta-analysis of cohort studies.Epidemiology and infection · 2020Pooled it
- A Systematic Review on the Effect of HIV Infection on the Pharmacokinetics of First-Line Tuberculosis Drugs.Clinical pharmacokinetics · 2019Pooled it
- d-Cycloserine Pharmacokinetics/Pharmacodynamics, Susceptibility, and Dosing Implications in Multidrug-resistant Tuberculosis: A Faustian Deal.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Pooled it
- Interethnic differences in pharmacokinetics of antibacterials.Clinical pharmacokinetics · 2015Pooled it
- Meta-analysis of clinical studies supports the pharmacokinetic variability hypothesis for acquired drug resistance and failure of antituberculosis therapy.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2012Pooled 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
- Pharmacokinetics of rifampin and isoniazid in tuberculosis-HIV-coinfected patients receiving nevirapine- or efavirenz-based antiretroviral treatment.Antimicrobial agents and chemotherapy · 2014Trial
- Pharmacokinetic Analysis of an Isoniazid Suspension Among Spanish Children Under 6 Years of Age.Antibiotics (Basel, Switzerland) · 2025Article
- GEODE: anFrontiers in pharmacology · 2025Article
- Optimized Sampling Strategies for Isoniazid in East Asian Pediatric Populations Using Population Pharmacokinetics-Informed Approaches.Drug design, development and therapy · 2025Article
- A Nanopore Sequencing-based Pharmacogenomic Panel to Personalize Tuberculosis Drug Dosing.American journal of respiratory and critical care medicine · 2024Article
- Application of the Hollow-Fiber Infection Model to Personalized Precision Dosing of Isoniazid in a Clinical Setting.Journal of Korean medical science · 2024Article
- Omadacycline pharmacokinetics/pharmacodynamics and efficacy against multidrug-resistantAntimicrobial agents and 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
- Isoniazid and rifampicin exposure during treatment in drug-susceptible TB.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2023Article
- Nouveau short-course therapy and morphism mapping for clinical pulmonaryAntimicrobial agents and chemotherapy · 2023Article
- Determining the Delamanid Pharmacokinetics/Pharmacodynamics Susceptibility Breakpoint Using Monte Carlo Experiments.Antimicrobial agents and chemotherapy · 2023Article
- Adequacy of the 10 mg/kg Daily Dose of Antituberculosis Drug Isoniazid in Infants under 6 Months of Age.Antibiotics (Basel, Switzerland) · 2023Article
33 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
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Isoniazid, administered as part of combination antituberculosis therapy, is responsible for most of the early bactericidal activity (EBA) of the regimen. However, the emergence of Mycobacterium tuberculosis resistance to isoniazid is a major problem. We examined the relationship between isoniazid exposure and M. tuberculosis microbial kill, as well as the emergence of resistance, in our in vitro pharmacodynamic model of tuberculosis. Since single-nucleotide polymorphisms of the N-acetyltransferase-2 gene lead to two different clearances of isoniazid from serum in patients, we simulated the isoniazid concentration-time profiles encountered in both slow and fast acetylators. Both microbial kill and the emergence of resistance during monotherapy were associated with the ratio of the area under the isoniazid concentration-time curve from 0 to 24 h (AUC(0-24)) to the isoniazid MIC. The time in mutant selection window hypothesis was rejected. Next, we utilized the in vitro relationship between the isoniazid AUC(0-24)/MIC ratio and microbial kill, the distributions of isoniazid clearance in populations with different percentages of slow and fast acetylators, and the distribution of isoniazid MICs for isonazid-susceptible M. tuberculosis clinical isolates in Monte Carlo simulations to calculate the EBA expected for approximately 10,000 patients treated with 300 mg of isoniazid. For those patient populations in which the proportion of fast acetylators and the isoniazid MICs were high, the average EBA of the standard dose was approximately 0.3 log(10) CFU/ml/day and was thus suboptimal. Our approach, which utilizes preclinical pharmacodynamics and the genetically determined multimodal distributions of serum clearances, is a preclinical tool that may be able to predict the EBAs of various doses of new antituberculosis drugs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.