Metabolism and disposition of prescription opioids: A review

A. Z. De Priest, B. L. Puet, A. C. Holt, A. Roberts, E. J. Cone

Research output: Contribution to journalReview articlepeer-review


Opioid analgesics are commonly prescribed for acute and chronic pain, but are subject to abuse. Consequently, toxicology testing programs are frequently implemented for both forensic and clinical applications. Understanding opioid metabolism and disposition is essential for assessing risk of toxicity and, in some cases, providing additional information regarding risk of therapeutic failure. Opioids significantly metabolized by the cytochrome P450 (CYP450) enzyme system may be subject to drug-drug interactions, including codeine, hydrocodone, oxycodone, fentanyl, meperidine, methadone, buprenorphine, and tramadol. CYP2D6 metabolism is polymorphic, and pharmacogenetic testing has been investigated for codeine, tramadol, oxycodone, and hydrocodone. CYP2B6 pharmacogenetic testing of methadone may reduce the risk of cardiac toxicity associated with the S-enantiomer. Opioids metabolized primarily by uridine 5′-diphospho-glucuronsyltransferase (UGT) enzymes include morphine, hydromorphone, dihydrocodeine, oxymorphone, levorphanol, and tapentadol. Parent and metabolite disposition is described for blood, oral fluid, and urine. Parent drug is most commonly detected in blood and oral fluid, whereas metabolites typically predominate in urine. Oral fluid/blood ratios exceed 1 for most opioids, making this an excellent alternative matrix for testing of this drug class. Metabolites of codeine, hydrocodone, and oxycodone are commercially available, and knowledge of metabolism is necessary for correct interpretation.

Original languageEnglish (US)
Pages (from-to)115-145
Number of pages31
JournalForensic Science Review
Issue number2
StatePublished - Jul 1 2018


  • Blood
  • Drug disposition
  • Metabolism
  • Opioids
  • Oral fluid
  • Pharmacokinetics
  • Urine

ASJC Scopus subject areas

  • Law


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