Acetylation Variability in Elderly Tunisians: Implications for Isoniazid Dose Individualization.

NAT2 slow acetylator phenotype → isoniazid accumulation → hepatotoxicity and neuropathy; rapid acetylator → underdosing and risk of therapeutic failure

476 Tunisian tuberculosis patients treated with isoniazid between 2019 and 2024 were phenotyped by the acetylation index (plasma concentration at 3h). The distribution of acetylator phenotypes (slow vs rapid) is characterized and its clinical implications evaluated, notably in elderly patients where pharmacokinetic variability and toxicity risk are increased. Results advocate for individualized NAT2 phenotype-based dosing in this population.

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NAT2 and isoniazid remain one of the best-documented yet least used gene-drug interactions in practice — notably in France where NAT2 genotyping is rarely offered before initiating antituberculosis treatment. This Tunisian cohort of 476 patients provides prevalence data in a population with high slow acetylator frequency.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 1/2 · Sample size: 1/1 · Publication status: 0/1 → Total: 6/10