ArticleAntimicrobial agents and chemotherapy2015
Population pharmacokinetic analysis of isoniazid, acetylisoniazid, and isonicotinic acid in healthy volunteers.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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The trial behind it
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
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 citations in OpenAlex.
- Pharmacokinetics of polymyxin B in different populations: a systematic review.European journal of clinical pharmacology · 2024Pooled it
- Association of genetic polymorphisms ofBMJ open · 2019Pooled it
- Pharmacokinetics and Drug-Drug Interactions of Isoniazid and Efavirenz in Pregnant Women Living With HIV in High TB Incidence Settings: Importance of Genotyping.Clinical pharmacology and therapeutics · 2021Trial
- Optimization of dosing regimens of isoniazid and rifampicin in children with tuberculosis in India.British journal of clinical pharmacology · 2019Trial
- Effect of efavirenz-based antiretroviral therapy and high-dose rifampicin on the pharmacokinetics of isoniazid and acetyl-isoniazid.The Journal of antimicrobial chemotherapy · 2019Trial
- Phenotyping of UGT1A1 Activity Using Raltegravir Predicts Pharmacokinetics and Toxicity of Irinotecan in FOLFIRI.PloS one · 2016Trial
- Pharmacogenomic heterogeneity ofAnnals of medicine · 2025Observational
- Case Report: Disseminated Tuberculosis After Kidney Transplantation.The American journal of tropical medicine and hygiene · 2024Article
- Precision Medicine Strategies to Improve Isoniazid Therapy in Patients with Tuberculosis.European journal of drug metabolism and pharmacokinetics · 2024Review
- 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
- Quantitative Analysis of Isoniazid and Its Four Primary Metabolites in Plasma of Tuberculosis Patients Using LC-MS/MS.Molecules (Basel, Switzerland) · 2022Article
- Population Pharmacokinetics and Pharmacodynamics of Isoniazid and its Metabolite Acetylisoniazid in Chinese Population.Frontiers in pharmacology · 2022Article
- Isonicotinylation is a histone mark induced by the anti-tuberculosis first-line drug isoniazid.Nature communications · 2021Article
- Development of a population pharmacokinetic model and Bayesian estimators for isoniazid in Tunisian tuberculosis patients.The pharmacogenomics journal · 2021Article
- A Model-Informed Method for the Purpose of Precision Dosing of Isoniazid in Pulmonary Tuberculosis.Clinical pharmacokinetics · 2021Article
- Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.Clinical pharmacokinetics · 2021Review
- Population pharmacokinetics of isoniazid and dose recommendations in Mexican patients with tuberculosis.International journal of clinical pharmacy · 2020Article
- Determination of isoniazid acetylation patterns in tuberculosis patients receiving DOT therapy under the Revised National tuberculosis Control Program (RNTCP) in India.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2020Article
- Population Pharmacokinetic Analysis of Isoniazid among Pulmonary Tuberculosis Patients from China.Antimicrobial agents and chemotherapy · 2020Article
- Isoniazid acetylation phenotypes in the Sudanese population; findings and implications.Journal of clinical tuberculosis and other mycobacterial diseases · 2019Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
In this study, we aimed to quantify the effects of the N-acetyltransferase 2 (NAT2) phenotype on isoniazid (INH) metabolism in vivo and identify other sources of pharmacokinetic variability following single-dose administration in healthy Asian adults. The concentrations of INH and its metabolites acetylisoniazid (AcINH) and isonicotinic acid (INA) in plasma were evaluated in 33 healthy Asians who were also given efavirenz and rifampin. The pharmacokinetics of INH, AcINH, and INA were analyzed using nonlinear mixed-effects modeling (NONMEM) to estimate the population pharmacokinetic parameters and evaluate the relationships between the parameters and the elimination status (fast, intermediate, and slow acetylators), demographic status, and measures of renal and hepatic function. A two-compartment model with first-order absorption best described the INH pharmacokinetics. AcINH and INA data were best described by a two- and a one-compartment model, respectively, linked to the INH model. In the final model for INH, the derived metabolic phenotypes for NAT2 were identified as a significant covariate in the INH clearance, reducing its interindividual variability from 86% to 14%. The INH clearance in fast eliminators was 1.9- and 7.7-fold higher than in intermediate and slow eliminators, respectively (65 versus 35 and 8 liters/h). Creatinine clearance was confirmed as a significant covariate for AcINH clearance. Simulations suggested that the current dosing guidelines (200 mg for 30 to 45 kg and 300 mg for >45 kg) may be suboptimal (3 mg/liter ≤ Cmax ≤ 6 mg/liter) irrespective of the acetylator class. The analysis established a model that adequately characterizes INH, AcINH, and INA pharmacokinetics in healthy Asians. Our results refine the NAT2 phenotype-based predictions of the pharmacokinetics for INH.
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