[Association between isoniazid induced hepatotoxicity and host N-acetyltransferase 2 polymorphisms]

Area of Science:

• Pharmacogenomics
• Tuberculosis Treatment
• Drug Metabolism

Background:

• Isoniazid (INH) is a cornerstone for treating drug-susceptible tuberculosis (TB).
• Pharmacokinetic variability, influenced by factors like drug absorption and liver metabolism, affects INH plasma concentrations.
• N-acetyltransferase 2 (NAT2) genetic polymorphism is a significant determinant of INH plasma levels.

Purpose of the Study:

• To clarify the relationship between host NAT2 genotype, its phenotypic expression, plasma INH concentrations, and associated adverse effects.
• To provide a basis for improved management strategies for INH therapy.
• To enhance tuberculosis treatment efficacy and minimize adverse drug reactions.

Main Methods:

• Review of existing literature on isoniazid pharmacokinetics and pharmacogenomics.
• Analysis of the impact of NAT2 genetic variations on INH metabolism and plasma concentrations.
• Correlation of genotype-phenotype data with clinical outcomes and adverse drug reactions.

Main Results:

• NAT2 genetic polymorphism significantly influences INH plasma concentrations, impacting treatment outcomes.
• Higher INH concentrations are linked to increased risk of hepatotoxicity and death.
• Current management of adverse INH reactions (dose reduction or discontinuation) may promote drug resistance.

Conclusions:

• Understanding the interplay between NAT2 genotype, INH plasma levels, and adverse effects is crucial for personalized tuberculosis treatment.
• Developing guidelines based on pharmacogenomic data can optimize INH efficacy and safety.
• Further research is needed to establish clear management protocols for INH therapy based on individual genetic profiles.