Letter To The Editor

Drs Pasic and Badgett raise an interesting question regarding phenobarbital/isoniazid (INH) interaction. The primary metabolic pathway of INH is acetylation by the enzyme N-acetyltransferase, and INH gets metabolized to acetylisoniazid. One of the metabolic products of acetylisoniazid (through hydrolysis) is monoacetylhydrazine, which can be converted by hepatic cytochrome P-450 enzymes to a hepatotoxic intermediate that covalently binds to hepatocytes, causing hepatic necrosis.1 A small amount of INH is directly hydrolyzed to a hepatotoxic hydrazine, which is also mediated by cytochrome P-450.