Which of the following drugs does not undergo acetylation?

• A. Isoniazid
• B. Chloramphenicol
• C. Hydralazine
• D. Sulfonamides

Answer: (B)

Acetylation is a liver phase II reaction where an acetyl group is transferred to certain drugs, typically at nitrogen atoms, making them more water-soluble for excretion. This pathway is carried out by N-acetyltransferase enzymes, and genetic differences mean some people are fast acetylators while others are slow, which can influence drug levels and toxicity for substrates of this route.

Isoniazid, hydralazine, and sulfonamides are classic drugs that are acetylated by NAT enzymes. They rely on this pathway for their metabolism, and variations in acetylation can affect their effects or risk of adverse reactions.

Chloramphenicol, on the other hand, is not primarily processed by acetylation. Its main inactivation pathway is glucuronidation, with less contribution from acetylation. This is why chloramphenicol is given as an example of a drug that does not undergo acetylation. For context, in neonates the limited capacity for glucuronidation explains the risk of gray baby syndrome when chloramphenicol is used.

So, the drug that does not undergo acetylation is chloramphenicol.