Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.

The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and aromatic amines. Notable drugs that undergo this process include isoniazid, procainamide, sulfonamides, neurotransmitters like catecholamines, and hormones.

Acetylation has crucial implications for drug toxicity. In certain situations, acetylation can lead to the creation of toxic metabolites. For instance, the acetylation of isoniazid can result in a tissue acylating intermediate that may cause liver toxicity. Furthermore, genetic variations known as acetylation polymorphisms can impact drug metabolism and response. These variations affect the enzymes responsible for acetylation, leading to individuals being either fast or slow acetylators. This distinction results in varied drug efficacy and toxicity levels.