Metabolism and Disposition of Prescription Opioids: A Review

Forensic Sci Rev. 2015 Jul;27(2):115-45.


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 cytochromeP450 (CYP450) enzyme system maybe subjectto 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.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / blood
  • Analgesics, Opioid / pharmacokinetics*
  • Analgesics, Opioid / urine
  • Animals
  • Biomarkers / blood
  • Biomarkers / urine
  • Biotransformation
  • Drug Monitoring
  • Humans
  • Pain / drug therapy*
  • Prescription Drugs / adverse effects
  • Prescription Drugs / pharmacokinetics*
  • Risk Assessment
  • Substance Abuse Detection
  • Substance-Related Disorders / blood
  • Substance-Related Disorders / diagnosis
  • Substance-Related Disorders / metabolism*
  • Substance-Related Disorders / urine


  • Analgesics, Opioid
  • Biomarkers
  • Prescription Drugs