glucuronidation

Glucuronidation is the body's most-used way of making a drug water-soluble enough to excrete. Think of clipping a small sugar-derived weight onto the drug: the molecule becomes heavier, more polar, and easy for the kidneys or bile to carry away.

Chemically, glucuronidation transfers glucuronic acid from the cofactor UDP-glucuronic acid onto the drug, a reaction catalyzed by UDP-glucuronosyltransferases (UGTs). It is the dominant phase II conjugation pathway and acts on drugs bearing hydroxyl, carboxyl, amino, or sulfhydryl groups. Common examples include the glucuronidation of morphine, paracetamol, and many NSAIDs.

Glucuronide conjugates are normally inactive and readily eliminated, but there are notable wrinkles. Newborns have immature UGT activity, which can cause toxic drug build-up; some glucuronides (such as morphine-6-glucuronide) are pharmacologically active; and glucuronides excreted in bile can be cleaved by gut bacteria, releasing the parent drug for reabsorption in enterohepatic circulation.