What is the impact of genetic polymorphisms on INH metabolism?

Genetic polymorphisms refer to variations in the DNA sequence among individuals, and these variations can significantly influence how drugs are metabolized in the body. In the case of isoniazid (INH), which is commonly used in the treatment of tuberculosis, genetic polymorphisms particularly affect the activity of the enzyme N-acetyltransferase 2 (NAT2).

Individuals can be classified into "slow" and "fast" acetylators based on these genetic variations. Slow acetylators metabolize isoniazid more slowly, which can lead to increased drug concentrations in the body. This may enhance the drug's efficacy against tuberculosis; however, it also raises the risk of toxicity and side effects due to prolonged exposure to the drug. Fast acetylators, on the other hand, metabolize the drug rapidly, which may diminish efficacy if the drug is cleared from the body too quickly.

Thus, genetic polymorphisms can lead to significant differences in both the effectiveness and the safety of INH therapy among individuals, impacting how well the drug works and how well it is tolerated. This demonstrates the importance of understanding genetic factors in personalized medicine, especially when prescribing medications like isoniazid.