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

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Tuberculosis Treatment

Background:

• Isoniazid acetylation phenotype and its link to age are poorly understood, especially in elderly populations.
• Elderly individuals may experience increased pharmacokinetic variability and toxicity risk with isoniazid.
• Characterizing isoniazid acetylation phenotypes in elderly Tunisian patients is essential for clinical management.

Purpose of the Study:

• To characterize isoniazid acetylation phenotypes in elderly Tunisian tuberculosis patients.
• To assess the clinical implications of different acetylation phenotypes.
• To evaluate the utility of phenotypic assessment for guiding isoniazid dosing.

Main Methods:

• Retrospective study of 476 Tunisian tuberculosis patients treated with isoniazid (2019-2024).
• Plasma isoniazid concentrations at 3 hours post-dose (C3) used to calculate the acetylation index (I3).
• Patients classified as rapid acetylators (RAs) or slow acetylators (SAs); statistical tests used to assess associations.

Main Results:

• Slow acetylators (68.1%) exhibited higher isoniazid exposure and supra-therapeutic concentrations (66.0% overall).
• Acetylator status significantly impacted dose adjustments (89.2% of SAs needed changes, mainly reductions).
• Adverse events were more frequent in SAs (44.1%) than RAs (15.1%); age correlated with adverse events, not phenotype.

Conclusions:

• High interindividual variability in isoniazid acetylation necessitates phenotypic assessment (I3) for individualized dosing.
• Phenotypic assessment is valuable in resource-limited settings lacking routine NAT2 genotyping.
• Further pharmacogenetic and pharmacokinetic studies are needed for precision therapy in high-risk elderly populations.