Codeine is considered a prodrug, since it is metabolised in vivo to the principal active analgesic agent morphine. It is, however, less potent than morphine since only about 10% of the codeine is converted. It also has a correspondingly lower dependence-liability than morphine.

Theoretically, a dose of approximately 200mg (oral) of codeine must be administered to give equivalent analgesia to 30mg (oral) of morphine (Rossi, 2004). It is not used, however, in single doses of greater than 60mg (and no more than 240mg in 24 hours) since there is a ceiling effect.

The conversion of codeine to morphine occurs in the liver and is catalysed by the cytochrome P450 enzyme CYP2D6. Approximately 6-10% of the Caucasian population have poorly functional CYP2D6 and codeine is virtually ineffective for analgesia in these patients (Rossi, 2004). Many of the adverse effects, however, are still experienced. Also, some medications are CYP2D6 inhibitors and reduce or even completely eliminate the efficacy of codeine. The most notorious of these are the selective serotonin reuptake inhibitors, such as fluoxetine (Prozac) and citalopram (Celexa).