SynthesisEuropean journal of clinical pharmacology2022
Influence of N-acetyltransferase 2 (NAT2) genotype/single nucleotide polymorphisms on clearance of isoniazid in tuberculosis patients: a systematic review of population pharmacokinetic models.
Synthesis in European journal of clinical pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 5 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 5 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Population Pharmacokinetics of Tigecycline and Implications for Individualized Therapy Optimization: A Systematic Review.Drug design, development and therapy · 2025Pooled it
- Pharmacogenomic insights into tuberculosis treatment shows the NAT2 genetic variants linked to hepatotoxicity risk: a systematic review and meta-analysis.BMC genomic data · 2024Pooled it
- Characteristics of isoniazid-induced psychosis: a systematic review of case reports and case series.European journal of clinical pharmacology · 2024Pooled it
- Efficacy, safety, and pharmacokinetics of isoniazid affected by NAT2 polymorphisms in patients with tuberculosis: A systematic review.Clinical and translational science · 2024Pooled it
- The pharmacogenetics of rosuvastatin and implications for treatment: a systematic review.PharmacogenomicsPooled it
- Population Pharmacokinetics of Amikacin in Non-Neonatal Pediatric Patients: A Scoping Review.European journal of drug metabolism and pharmacokinetics · 2026Article
- Altered Pharmacokinetics and Delayed Sputum Conversion in Tuberculosis Patients Co-Infected With HIV.Tropical medicine & international health : TM & IH · 2026Observational
- Regimen-Specific Population Pharmacokinetics of Isoniazid with and Without Rifamycin: A Bayesian Modeling Analysis of 6H, 3HR, and 3H2P2 Regimens.Pharmaceutics · 2026Article
- Article
- Pharmacogenomic heterogeneity ofAnnals of medicine · 2025Observational
- Effect of Genetic Variants on Rosuvastatin Pharmacokinetics in Healthy Volunteers: Involvement ofInternational journal of molecular sciences · 2024Article
- Precision Medicine Strategies to Improve Isoniazid Therapy in Patients with Tuberculosis.European journal of drug metabolism and pharmacokinetics · 2024Review
- Genetic Variation inPharmaceutics · 2024Article
- Prediction Models for Adverse Drug Reactions During Tuberculosis Treatment in Brazil.The Journal of infectious diseases · 2024Article
- Model-Informed Precision Dosing of Isoniazid: Parametric Population Pharmacokinetics Model Repository.Drug design, development and therapy · 2024Article
- Application of a physiologically based pharmacokinetic model to predict isoniazid disposition during pregnancy.Clinical and translational science · 2023Article
- Management of Polypharmacy and Potential Drug-Drug Interactions in Patients with Mycobacterial Infection: A 1-Year Experience of a Multidisciplinary Outpatient Clinic.Antibiotics (Basel, Switzerland) · 2023Article
- Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeSignificant pharmacokinetic variabilities have been reported for isoniazid across various populations. We aimed to summarize population pharmacokinetic studies of isoniazid in tuberculosis (TB) patients with a specific focus on the influence of N-acetyltransferase 2 (NAT2) genotype/single-nucleotide polymorphism (SNP) on clearance of isoniazid.
methodsA systematic search was conducted in PubMed and Embase for articles published in the English language from inception till February 2022 to identify population pharmacokinetic (PopPK) studies of isoniazid. Studies were included if patient population had TB and received isoniazid therapy, non-linear mixed effects modelling, and parametric approach was used for building isoniazid PopPK model and NAT2 genotype/SNP was tested as a covariate for model development.
resultsA total of 12 articles were identified from PubMed, Embase, and hand searching of articles. Isoniazid disposition was described using a two-compartment model with first-order absorption and linear elimination in most of the studies. Significant covariates influencing the pharmacokinetics of isoniazid were NAT2 genotype, body weight, lean body weight, body mass index, fat-free mass, efavirenz, formulation, CD4 cell count, and gender. Majority of studies conducted in adult TB population have reported a twofold or threefold increase in isoniazid clearance for NAT2 rapid acetylators compared to slow acetylators.
conclusionThe variability in disposition of isoniazid can be majorly attributed to NAT2 genotype. This results in a trimodal clearance pattern with a multi-fold increase in clearance of NAT2 rapid acetylators compared to slow acetylators. Further studies exploring the generalizability/adaptability of developed PopPK models in different clinical settings are required.
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