Answer to Question #23605 in Biology for BIRHANU SIMON

Question #23605
Which one is more susceptible: slow or fast acetylator by Isoniazid drug side effect?
Expert's answer
The most widely accepted theory is that isoniazid metabolism produces reactive metabolites that bind to and damage cellular macromolecules in the liver. Most isoniazid is acetylated and then further hydrolyzed to isonicotinic acid and acetylhydrazine . Persons with the rapid acetylator phenotype have been proposed to be more likely to display toxicity; however, most studies have failed to show such a relationship.

On the contrary, some studies suggest that people who are slow acetylators are at greater risk, suggesting that slow metabolism results in& diversion of isoniazid metabolism to an alternate (eg, cytochrome P-450–mediated) pathway that may produce a toxic metabolite. This latter interpretation is supported by observations that drugs that induce cytochrome P-450 levels (including rifampin, which often is prescribed together with isoniazid) appear to increase the risk of isoniazid toxicity.
bottom line
fast acetylators = drug resistance
slow acetylators = hepatotoxicity

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