Oral opioid metabolism and pharmacogenetics

L. Malan*, M. Lundie, D. Engler

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Opioid analgesics are widely used as the standard of care for the management of moderate to severe nociceptive pain. The opioids' analgesic properties mainly emanate from stimulation of the µ-receptors, which are encoded by the OPRM1 gene. Most opioids are fat-soluble, requiring conversion to water-soluble compounds for excretion, but for some opioids, namely tramadol and codeine, hepatic metabolism is necessary for their bioactivation into more potent analgesics. Hepatic biotransformation generally occurs as Phase I and Phase II metabolism. The highly polymorphic nature of the genes, coding for Phase I and II enzymes involved in the metabolism and bioactivation of opioids, suggests potential interindividual variation in patient response in terms of efficacy and safety. Patients can be classified by their genetic ability to metabolise medication. The inherent differences in the genes that encode the CYP450 enzymes, particularly CYP3A4 and CYP2D6, can affect the metabolic capacity of an individual, leading to over- or underexposure to an opioid, making opioid pharmacokinetics and pharmacodynamics variable between individuals. Other medications that also utilise the CYP450 pathway can lead to interactions. In addition to pharmacogenomics, other factors like age, ethnicity and renal impairment also contribute to differences in opioid metabolism and variation in patient response. This article provides a review of the metabolism of commonly prescribed oral opioids, and pharmacogenetic considerations.

Original languageEnglish
Pages (from-to)21-28
Number of pages8
JournalSA Pharmaceutical Journal
Issue number2
Publication statusPublished - 2019


  • Cytochrome P450
  • Individualised pain management
  • Opioid metabolism
  • Opioids
  • Pharmacogenetics


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