March 2018

Oxycodone

Dr. Joseph E. Graas, Scientific Director
Dr. Edward Moore, Medical Director
Dr. Paul Robandt, Scientific Director

Oxycodone is a semisynthetic keto-opioid first synthesized from thebaine in 1917 in Germany.  Thebaine is found naturally in poppy straw.  In 2013 Australia was the main producer, followed by Spain and France, accounting for 99% of global production.1   Treatment of thebaine with m-chloroperoxybenzoic acid in acetic acid and trifluoroacetic acid, then hydrogenation with a catalyst results in the desired oxycodone.2

Pharmacologically, oxycodone shares the same characteristics of morphine.  It is a potent analgesic, with associated feelings of euphoria and anxiolysis.  Side effects include constipation, nausea, vomiting, dizziness and respiratory depression.  It is respiratory depression that causes death in opioid overdose cases.  When choosing an opioid for treatment, morphine is generally considered first.  Morphine may be undesirable due to adverse patient effects or low bioavailability (20-40% orally).  Oxycodone is 80% bioavailable orally and the half-life is similar to morphine, therefore, it is easier to convert patients from morphine to oxycodone in treatment compared to other opioids.

Oxycodone is a full agonist for the µ-opioid receptor and has almost no affinity for the δ- and κ-opioid receptors.  After an oral dose of oxycodone, the onset of action is 10-30 minutes with peak plasma levels in 30-60 minutes.3   Oxycontin® (Purdue Pharma), an oral sustained-release formulation containing oxycodone, delivers peak plasma levels in about 180 minutes.

Oxycontin® plays a key role in the current US opioid crisis.  It was first developed in 1995 as a sustained-release form of oxycodone.  Since it is sustained-release, it contains much more oxycodone than a tablet of oxycodone alone.  A typical single dose of oxycodone is 5 milligrams, while an Oxycontin® tablet can contain 10, 20, 40 or 80 milligrams of pure oxycodone.  People who wanted larger doses of oxycodone were crushing the Oxycontin® tablets and snorting them or extracting the contents and injecting the oxycodone.  To prevent this, manufacturers are developing crush-proof tablets or tablets formulated with microspheres that maintain the extended-release properties even when crushed.4,5 

There is a large amount of illegal traffic in oxycodone tablets, extended-release or otherwise.  People who seek opioids are likely to seek any substance that relieves their addiction, including heroin.  In many instances, it may be easier for people to seek and find heroin than Oxycontin®.  The current heroin crisis, compounded with the recent addition of fentanyl, is a result of skyrocketing painkiller prescriptions in the 1990s and 2000s era.  Another very insidious pathway to drug abuse is the relative ease which children and young adults have access to opioids used for analgesia.6,7

Oxycodone can be metabolized to oxymorphone.  In an immunoassay class screen, it does not appreciably cross-react with other opioids, nor does it interfere with other opioids in a mass spectrometer during the confirmation process.  Testing for oxycodone is specific when an immunoassay class screen is confirmed with a mass spectrometric technique (HPLC/MS/MS or GC/MS).

 References

  1. Narcotic Drugs: Estimated World Requirements for 2015; Statistics for 2013 (PDF). International Narcotics Control Board. United Nations International Narcotics Control Board. 2015. p. 151
  2. 1917: German Patent 296916
  3. Howard Smith; Steven Passik (25 April 2008). Pain and Chemical Dependency. Oxford University Press, USA. pp. 195–
  4. Moorman-Li, R., et.al., A Review of Abuse-Deterrent Opioids For Chronic Nonmalignant Pain, Pharmacy and Therapeutics, 2012 Jul; 37(7): 412–418.
  5. 5.  Gudin, J., Oxycodone DETERx®: A Novel Abuse-Deterrent, Extended-Release Analgesic Option for the Treatment of Patients with Chronic Pain, Pain Ther. 2016 Dec; 5(2): 171–186
  6. National Institute of Drug Abuse, https://www.drugabuse.gov/trends-statistics/monitoring-future/monitoring-future-study-trends-in-prevalence-various-drugs, 2017
  7. National Institute of Drug Abuse, https://www.drugabuse.gov/trends-statistics/monitoring-future/monitoring-future-study-trends-in-prevalence-various-drugs, 2016