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Letter to the Editor
Editor, – Thank you to Dr Murnion for the excellent review of combination analgesics (Aust Prescr 2010;33:113-5). My understanding of the efficacy of codeine is that it is predominantly a prodrug and that the major analgesic effects derive through the actions of two of its major metabolites, codeine-6-glucuronide and morphine.
Under normal circumstances, most of the codeine is metabolised to codeine-6-glucuronide, with perhaps 10% appearing as morphine. The latter is produced through the action of cytochrome P450 2D6. It has been noted that a small proportion of the population have little CYP2D6 and receive less analgesia than expected. A similar effect is noted in those taking drugs such as fluoxetine which inhibit CYP2D6.
The converse is true for those hyper-metabolisers who have multiple copies of CYP2D6 or who take drugs such as dexamethasone which induce the enzyme.
Given the comments by Dr Murnion regarding the usefulness of paracetamol or a non-steroidal anti-inflammatory drug in conjunction with morphine, could she please comment on the possibility of better prescribing codeine (in combination or otherwise) based on the patient's CYP2D6 status.
Senior hospital scientist
Toxicology Unit – PaLMS
North Ryde, NSW
- Macintyre PE, Scott DA, Schug SA, Visser EJ, Walker SM, editors; APM:SE Working Group of the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine. Acute Pain Management: Scientific Evidence. 3rd ed. Melbourne: ANZCA & FPM; 2010.
- Bachmann KA. Genotyping and phenotyping the cytochrome p-450 enzymes. Am J Ther 2002;9:309-16.