Where is codeine metabolised

In these patients, a 30 mg dose of codeine phosphate would yield approximately 1. Ultra-rapid metabolisers convert codeine to morphine very efficiently, which can lead to morphine toxicity, such as respiratory depression and death. Both codeine and morphine are excreted into breast milk. This is of particular concern for breastfeeding mothers who are ultra-rapid metabolisers.

Exposure of the infant to breast milk containing morphine may lead to opioid toxicity in the infant, with the potential for respiratory depression and death. Furthermore, opioid toxicity in the mother such as somnolence may compromise her ability to identify signs of opioid toxicity in her infant.

The review identified 64 cases of serious breathing problems, including 24 deaths, associated with codeine-containing medicines in children aged under 18 years 2.

Many of these cases concerned children with obstructive sleep apnoea who received codeine after surgery to remove tonsils or adenoids 3. Since these children already had underlying breathing problems, they may have been particularly sensitive to morphine-induced respiratory depression. In New Zealand, 53 deaths were recorded in the National Coronial Information System for the period 1 January to 31 December in which codeine was assessed as the primary contributor JS Fountain, personal communication, April This subset of individuals may experience undesirable effects, without any clinical analgesic benefit.

This is potentially very hazardous: Gasche et al. The patient was later identified as being a CYP2D6 ultra-rapid metaboliser. Opioid use in palliative care: selection, initiation and optimisation. The Pharmaceutical Journal ; Compound summary: Codeine. British National Formulary online. Vree T, Verwey-van W. Pharmacokinetics and metabolism of codeine in humans. Biopharm Drug Dispos ; 13 — Biochem Biophys Res Commun ; —6. Anderson B. Is it farewell to codeine? Arch Dis Child ; 98 —8. Codeine analgesia is due to codeineglucuronide, not morphine.

Int J Clin Pract ; 54 —8. N Engl J Med ; — Haufroid V, Hantson P. CYP2D6 genetic polymorphisms and their relevance for poisoning due to amfetamines, opioid analgesics and antidepressants. Clin Toxicol Phila ; 53 — Variability in response to drugs.

In: Palliative Care Formulary. London: : Pharmaceutical Press Wu AHB. Drug metabolizing enzyme activities versus genetic variances for drug of clinical pharmacogenomic relevance. Clin Proteom ; 8. Published Online First: 30 March Same incidence of adverse drug events after codeine administration irrespective of the genetically determined differences in morphine formation.

Pain ; 76 — Codeine phosphate. Codeine is a widely used opioid analgesic and is sometimes given post-operatively for pain relief in children.

Codeine has a very low affinity for opioid receptors and is partially metabolised to morphine in the liver via the cytochrome P enzyme 2D6 CYP2D6.

Genetic differences in the expression of the CYP2D6 enzyme results in differences in the extent to which codeine is metabolised. Patients deficient in or lacking this enzyme cannot convert codeine to morphine and therefore may not obtain adequate analgesic pain relief. Conversely, patients who metabolise codeine very rapidly ultra-rapid metabolisers are at increased risk of developing adverse effects of opioid toxicity, even at low doses. The prevalence in Maori and Pacific people is not known.