drugmetabolite

Drug metabolites are chemical products formed when a drug undergoes biotransformation in the body. Metabolism is mainly conducted in the liver, but also occurs in other tissues such as the intestines and kidneys. The goal of metabolism is to convert lipophilic drugs into more water-soluble forms to facilitate excretion, thereby aiding elimination from the body.

Metabolic processes are often described in two phases. Phase I involves functionalization reactions—oxidation, reduction, and hydrolysis—typically mediated by enzymes such as the cytochrome P450 family. Phase II consists of conjugation reactions, attaching polar groups like glucuronide or sulfate, to further increase solubility and excretion.

Metabolites can be inactive, active, or toxic. Some drugs are prodrugs whose therapeutic effects depend on metabolite formation. Others produce toxic metabolites that contribute to adverse effects, such as the hepatotoxic metabolite NAPQI derived from acetaminophen in overdoses. Individual differences in metabolite formation arise from genetic variations (for example, CYP2D6 polymorphisms), age, liver or kidney function, and interactions with other drugs or foods, all of which can influence efficacy and safety.

Clinically, drug metabolites are important for pharmacokinetics, therapeutic drug monitoring, and toxicology. Analytical approaches frequently measure specific metabolites, which may be more detectable or longer-lasting than the parent compound. Examples include the conversion of codeine to morphine and the formation of various glucuronide conjugates for several drugs.