Conjugation

• Some drugs are primarily metabolised by conjugation where another molecule is covalently bonded to the drug to form a polar metabolite, which is usually inactive and renally excreted.
• Conjugation can be with glucuronic acid, sulphate, glutathione, amino acids, acetate, or a methyl group.
• The most common is glucuronidation by UDP-glucuronosyltransferases (UGTs). Expression of UGTs are genetically determined.
• Conjugation is inducible and subject to inhibition.
• Drugs may be metabolised by more than one enzyme.
• The following lists are not exhaustive and do not identify specific enzymes.

Substrates

Main drug classes predominantly metabolised by conjugation include:

• beta agonists, some benzodiazepines, some opioids, some cytotoxics.

Main Drugs

*to active metabolites

Inhibitors of glucuronidation (increase plasma concentrations of substrates)

There are multiple enzymes and the following inhibit some, not all.

Inducers of glucuronidation (decrease plasma concentrations of substrates)

Topic Code: 93355

must be prescribed or recommended by a consultant.