Codeine-6-glucuronide

Codeine-6-glucuronide (C6G) is a metabolite of codeine that is formed in the body after the administration of codeine. It is a major metabolite of codeine, accounting for approximately 60-70% of the total metabolites excreted in the urine.

Pharmacology

C6G is formed in the body by the action of the enzyme UDP-glucuronosyltransferase (UGT), specifically UGT2B7. This enzyme is responsible for the glucuronidation of many drugs and endogenous substances, including codeine. The glucuronidation process involves the addition of a glucuronic acid molecule to the drug, which increases its water solubility and facilitates its excretion in the urine.

C6G has been shown to have analgesic effects in its own right, although these are less potent than those of codeine itself. The analgesic effects of C6G are thought to be mediated by its action on the mu-opioid receptor, the same receptor that is targeted by codeine.

Clinical significance

The formation of C6G from codeine is an important factor in the variability of the analgesic response to codeine. Some individuals are poor metabolizers of codeine, due to genetic variations in the UGT2B7 enzyme. These individuals produce less C6G and may therefore experience less analgesic effect from codeine.

In addition, the formation of C6G may contribute to the side effects of codeine. C6G has been shown to cause respiratory depression, a common side effect of opioids. However, the extent to which C6G contributes to the side effects of codeine is not fully understood.

See also

• Codeine
• Glucuronidation
• Opioid
• Pharmacogenetics