Personalizing anti-tubercular medication in children using Therapeutic Drug Monitoring

The research study focuses on personalizing medicine for children undergoing treatment for tuberculosis (TB) with Isoniazid (INH). TB is a major global health issue, particularly in children from low-income populations, with India seeing over 340,000 cases annually. INH is a crucial first-line anti-TB drug, typically administered over at least six months. The effectiveness of INH hinges on proper dosing, which must balance efficacy with minimal side effects such as liver toxicity and nerve damage.

INH metabolism in the body varies significantly among individuals due to genetic and non-genetic factors. Amongst the genetic factors, a key genetic determinant is the presence of polymorphisms in the N-acetyltransferase 2 (NAT2) enzyme. These variations classify individuals as slow, intermediate, or fast acetylators, affecting how quickly INH is processed in the body. This variability influences plasma levels of the drug, thereby impacting both its therapeutic efficacy and the likelihood of adverse effects.

Non-genetic factors, including age, gender, body weight, liver function, and other concurrent medications, which can further contribute to differences in how children metabolize INH. Age, differences in body composition amongst children and from adults necessitates tailored dosing strategies. The study aims to explore these differences and how NAT2 polymorphisms specifically affect children receiving INH. The goal is to optimize dosing by considering these genetic differences, thereby enhancing the efficacy of TB treatment while minimizing the risk of side effects like hepatotoxicity and neuropathy.

The primary objective of the study is to examine the relationship between NAT2 genotypes and INH acetylation in children. This could lead to more personalized treatment strategies in pediatric TB care, potentially improving therapeutic outcomes and reducing adverse drug reactions. Thus , this study involves collecting data from children receiving INH, conducting genetic tests to determine their NAT2 genotype, and monitoring their plasma INH levels. Adverse effects, especially liver toxicity, will be closely tracked. Statistical analyses will then identify correlations between the children’s genotypes, INH plasma levels, and clinical outcomes.

This research is expected to yield valuable insights into how NAT2 polymorphisms influence INH metabolism in paediatric TB patients. The findings could pave the way for genotype-guided dosing strategies, enhancing the safety and effectiveness of TB treatment in pediatric populations. Ultimately, this study will contribute to the valuable insights and assist in the effort of advancing personalized medicine in paediatric care, ensuring that each child receives the most appropriate treatment based on their genetic profile.