Codeine, CYP2D6 phenotypes and morphine

Codeine is metabolised to morphine by CYP2D6.
CYD2D6 displays huge variation in activity due to genetic polymorphism.

4 phenotypes of expression are identified depending on the level of activity

• UMs: Ultrarapid metabolisers
• EMs: Extensive metabolisers (Most Common)
• IMs: Intermediate metabolisers
• PMs: Poor metabolisers

Morphine is formed at a very fast pace in ultrarapid metabolisers.
In adults with ultra rapid metabolisation: if codeine is administered at therapeutic doses then resulting levels of morphine is unlikely to cause respiratory depression. But the possibility increases substantially in overdosage.
In lactating mothers with ultra rapid metabolisation: codeine administered at therapeutic doses may result in high levels of morphine in milk; there are case reports of respiratory depression occurring in infants of such mothers.