Oxycodone

Effects

Pain reliefRespiratory depressionSedationConstipationCough suppressionDecreased libidoDifficulty urinatingItchinessNauseaPupil constrictionStomach crampsAppetite suppressionEuphoriaAnxiety suppressionDream potentiation TS

Overview

Oxycodone (also known under brand names including Roxicodone, OxyContin, Percocet, Oxecta, OxyIR, Endone, Oxynorm, Faroxy and OxyNEO) is a semi-synthetic opioid synthesized from poppy-derived thebaine. It is a narcotic analgesic within the morphinan chemical class and is generally indicated for relief of moderate to severe pain. It was developed in 1916 in Germany as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids.[1][2][3] PW

A semisynthetic opioid analgesic developed in 1917, prescribed primarily for pain management. It has become extremely popular as a recreational drug in some areas, and carries a high potential for addiction. Reported as being a little more 'stimulating' than other opioids.[4–13] TS

Oxycodone, sold under the brand names Roxicodone and OxyContin (which is the extended-release form) among others, is a semi-synthetic opioid used medically for the treatment of moderate to severe pain. It is a highly addictive and commonly abused drug. It is usually taken orally, and is available in immediate-release and controlled-release formulations. Onset of pain relief typically begins within fifteen minutes and lasts for up to six hours with the immediate-release formulation. In the United Kingdom, it is available by injection. Combination products are also available with paracetamol (acetaminophen), ibuprofen, naloxone, naltrexone, and aspirin.[14–17] WP

Common side effects include euphoria, constipation, nausea, vomiting, loss of appetite, drowsiness, dizziness, itching, dry mouth, and sweating. Side effects may also include addiction and dependence, substance abuse, irritability, depression or mania, delirium, hallucinations, hypoventilation, gastroparesis, bradycardia, and hypotension. Those allergic to codeine may also be allergic to oxycodone. Opioid withdrawal may occur if rapidly stopped. Oxycodone acts by activating the μ-opioid receptor. When taken by mouth, it has roughly 1.5 times the effect of the equivalent amount of morphine.[15][18][19] WP

Oxycodone was originally produced from the opium poppy opiate alkaloid thebaine in 1916 in Germany. One year later, it was used medically for the first time in Germany. Oxycodone is available as a generic medication. In 2023, it was the 49th most commonly prescribed medication in the United States, with more than 13 million prescriptions. A number of abuse-deterrent formulations are available, such as in combination with naloxone or naltrexone.[3][15][16][20][21][22] WP

History

History

Martin Freund and (Jakob) Edmund Speyer of the University of Frankfurt in Germany published the first synthesis of oxycodone from thebaine in 1916. When Freund died, in 1920, Speyer wrote his obituary for the German Chemical Society. Speyer, born to a Jewish family in Frankfurt am Main in 1878, became a victim of the Holocaust. He died on 5 May 1942, the second day of deportations from the Lodz Ghetto; his death was noted in the ghetto's chronicle.[27–30] WP

The first clinical use of the drug was documented in 1917, the year after it was first developed. It was first introduced to the U.S. market in May 1939. In early 1928, Merck introduced a combination product containing scopolamine, oxycodone, and ephedrine under the German initials for the ingredients SEE, which was later renamed Scophedal (SCOpolamine, ePHEDrine, and eukodAL) in 1942. It was last manufactured in 1987 but can be compounded. This combination is essentially an oxycodone analogue of the morphine-based "twilight sleep", with ephedrine added to reduce circulatory and respiratory effects. The drug became known as the "Miracle Drug of the 1930s" in Continental Europe and elsewhere and it was the Wehrmacht's choice for a battlefield analgesic for a time. The drug was expressly designed to provide what the patent application and package insert referred to as "very deep analgesia and profound and intense euphoria" as well as tranquillisation and anterograde amnesia useful for surgery and battlefield wounding cases. Oxycodone was allegedly chosen over other common opiates for this product because it had been shown to produce less sedation at equianalgesic doses compared to morphine, hydromorphone (Dilaudid), and hydrocodone (Dicodid).[28][31][32][33] WP

During Operation Himmler, Skophedal was also reportedly injected in massive overdose into the prisoners dressed in Polish Army uniforms in the staged incident on 1 September 1939 which opened the Second World War.[32][34] WP

The personal notes of Adolf Hitler's physician, Theodor Morell, indicate Hitler received repeated injections of "Eukodal" (oxycodone; produced by Merck) and Scophedal, as well as Dolantin (pethidine), codeine, and morphine less frequently; oxycodone could not be obtained after late January 1945.[35][36] WP

In the United States, the Controlled Substances Act (CSA) was passed by the United States Congress and signed into law by President Richard Nixon on 27 October 1970. The passing of the CSA resulted in all products containing oxycodone being classified as a Schedule II controlled substance.[37][38] WP

In the early 1990s, Purdue Pharma, a privately held company based in Stamford, Connecticut, developed a controlled-release version of oxycodone: the prescription painkiller OxyContin ("contin" being short for "continuous", reflecting a longer duration of pain relief). It was approved by the FDA in 1995 after no long-term studies and no assessment of its addictive capabilities. David Kessler, the FDA commissioner at the time, later said of the approval of OxyContin: "No doubt it was a mistake. It was certainly one of the worst medical mistakes, a major mistake." Upon its release in 1995, OxyContin was hailed as a medical breakthrough, a long-lasting narcotic that could help patients with moderate to severe pain. The drug became a blockbuster and has reportedly generated some US$35 billion in revenue for Purdue.[39][40][41] WP

Legal status

Opioid epidemic

Oxycodone, like other opioid analgesics, tends to induce feelings of euphoria, relaxation, and reduced anxiety in those who are occasional users. The abuse of oxycodone, as well as related opioids more broadly, is not unique to the United States and it is a common drug of abuse globally.[42][43][44] WP

United states

Oxycodone is the most widely recreationally used opioid in America. In the United States, more than 12 million people use opioid drugs recreationally. The U.S. Department of Health and Human Services estimates that about 11 million people in the U.S. consume oxycodone in a non-medical way annually.[45][46] WP

Opioids were responsible for 49,000 of the 72,000 drug overdose deaths in the U.S. in 2017. In 2007, about 42,800 emergency room visits occurred due to "episodes" involving oxycodone. In 2008, recreational use of oxycodone and hydrocodone was involved in 14,800 deaths. Some of the cases were due to overdoses of the acetaminophen component, resulting in fatal liver damage.[47][48][49] WP

In September 2013, the US Food and Drug Administration (FDA) released updated labeling guidelines for long-acting and extended-release opioids requiring manufacturers to remove moderate pain as an indication for use, instead stating the drug is for "pain severe enough to require daily, around-the-clock, long term opioid treatment". The updated labeling does not restrict physicians from prescribing opioids for moderate pain, as needed.[45][50] WP

Reformulated OxyContin is causing some recreational users to change to heroin, which is cheaper and easier to obtain.[51] WP

Lawsuits

In October 2017, The New Yorker published a story on Mortimer Sackler and Purdue Pharma regarding their ties to the production and manipulation of the oxycodone markets. The article links Raymond and Arthur Sackler's business practices with the rise of direct pharmaceutical marketing and eventually to the rise of addiction to oxycodone in the United States. The article implies that the Sackler family bears some responsibility for the opioid epidemic in the United States. In 2019, The New York Times ran a piece confirming that Richard Sackler, the son of Raymond Sackler, told company officials in 2008 to "measure our performance by Rx's by strength, giving higher measures to higher strengths". This was verified with documents tied to a lawsuit – which was filed by the Massachusetts attorney general, Maura Healey – claiming that Purdue Pharma and members of the Sackler family knew that high doses of OxyContin over long periods would increase the risk of serious side effects, including addiction. Despite Purdue Pharma's proposal for a US$12 billion settlement of the lawsuit, the attorneys general of 23 states, including Massachusetts, rejected the settlement offer in September 2019.[39][52][53][54] WP

Australia

The non-medical use of oxycodone existed since the early 1970s, but by 2015, 91% of a national sample of injecting drug users in Australia had reported using oxycodone, and 27% had injected it in the last six months.[55] WP

Canada

Opioid-related deaths in Ontario had increased by 242% from 1969 to 2014. By 2009 in Ontario there were more deaths from oxycodone overdoses than from cocaine overdoses. Deaths from opioid pain relievers had increased from 13.7 deaths per million residents in 1991 to 27.2 deaths per million residents in 2004. The non-medical use of oxycodone in Canada became a problem. Areas where oxycodone is most problematic are Atlantic Canada and Ontario, where its non-medical use is prevalent in rural towns and in many smaller to medium-sized cities. Oxycodone is also widely available across Western Canada, but methamphetamine and heroin are more serious problems in larger cities, while oxycodone is more common in rural towns. Oxycodone is diverted through doctor shopping, prescription forgery, pharmacy theft, and overprescription.[56–60] WP

The recent formulations of oxycodone, particularly Purdue Pharma's crush-, chew-, injection- and dissolve-resistant OxyNEO which replaced the banned OxyContin product in Canada in early 2012, have led to a decline in the recreational use of this opiate but have increased the recreational use of the more potent drug fentanyl. According to a Canadian Centre on Substance Abuse study quoted in Maclean's magazine, there were at least 655 fentanyl-related deaths in Canada in five years.[61][62][63] WP

In Alberta, the Blood Tribe police claimed that from the fall of 2014 through January 2015, oxycodone pills or a lethal fake variation referred to as Oxy 80s containing fentanyl made in illegal labs by members of organized crime were responsible for ten deaths on the Blood Reserve, which is located southwest of Lethbridge, Alberta. Province-wide, approximately 120 Albertans died from fentanyl-related overdoses in 2014.[64][65] WP

United kingdom

Prescriptions of Oxycodone rose in Scotland by 430% between 2002 and 2008, prompting fears of usage problems that would mirror those of the United States. The first known death due to overdose in the UK occurred in 2002.[66][67] WP

Preventive measures

In August 2010, Purdue Pharma reformulated their long-acting oxycodone line, marketed as OxyContin, using a polymer, Intac, to make the pills more difficult to crush or dissolve in water to reduce non-medical use of OxyContin. Inactive ingredients/excipients are butylated hydroxytoluene (BHT), hypromellose, polyethylene glycol 400, polyethylene oxide, magnesium stearate, and titanium dioxide. The FDA approved relabeling the reformulated version as abuse-resistant in April 2013.[68–73] WP

Pfizer manufactures a preparation of short-acting oxycodone, marketed as Oxecta, which contains inactive ingredients, referred to as tamper-resistant Aversion Technology. Approved by the FDA in the U.S. in June 2011, the new formulation, while not being able to deter oral recreational use, makes crushing, chewing, snorting, or injecting the opioid impractical because of a change in its chemical properties.[74][75] WP

Legal status

Oxycodone is subject to international conventions on narcotic drugs. In addition, oxycodone is subject to national laws that differ by country. The 1931 Convention for Limiting the Manufacture and Regulating the Distribution of Narcotic Drugs of the League of Nations included oxycodone. The 1961 Single Convention on Narcotic Drugs of the United Nations, which replaced the 1931 convention, categorized oxycodone in Schedule I. Global restrictions on Schedule I drugs include "limit[ing] exclusively to medical and scientific purposes the production, manufacture, export, import, distribution of, trade in, use and possession of" these drugs; "requir[ing] medical prescriptions for the supply or dispensation of [these] drugs to individuals"; and "prevent[ing] the accumulation" of quantities of these drugs "in excess of those required for the normal conduct of business".[76][77] WP

Australia

Oxycodone is in Schedule I (derived from the Single Convention on Narcotic Drugs) of the Commonwealth's Narcotic Drugs Act 1967. In addition, it is in Schedule 8 of the Australian Standard for the Uniform Scheduling of Drugs and Poisons ("Poisons Standard"), meaning it is a "controlled drug... which should be available for use but require[s] restriction of manufacture, supply, distribution, possession and use to reduce abuse, misuse and physical or psychological dependence".[78][79] WP

Canada

Oxycodone is a controlled substance under Schedule I of the Controlled Drugs and Substances Act (CDSA).[80] WP

In February 2012, Ontario passed legislation to allow the expansion of an already existing drug-tracking system for publicly funded drugs to include those that are privately insured. This database will function to identify and monitor patient's attempts to seek prescriptions from multiple doctors or retrieve them from multiple pharmacies. Other provinces have proposed similar legislation, while some, such as Nova Scotia, have legislation already in effect for monitoring prescription drug use. These changes have coincided with other changes in Ontario's legislation to target the misuse of painkillers and high addiction rates to drugs such as oxycodone. As of 29 February 2012, Ontario passed legislation delisting oxycodone from the province's public drug benefit program. This was a first for any province to delist a drug based on addictive properties. The new law prohibits prescriptions for OxyNeo except to certain patients under the Exceptional Access Program including palliative care and in other extenuating circumstances. Patients already prescribed oxycodone will receive coverage for an additional year for OxyNeo, and after that, it will be disallowed unless designated under the exceptional access program.[81] WP

Much of the legislative activity has stemmed from Purdue Pharma's decision in 2011 to begin a modification of OxyContin's composition to make it more difficult to crush for snorting or injecting. The new formulation, OxyNeo, is intended to be preventive in this regard and retain its effectiveness as a painkiller. Since introducing its Narcotics Safety and Awareness Act, Ontario has committed to focusing on drug addiction, particularly in the monitoring and identification of problem opioid prescriptions, as well as the education of patients, doctors, and pharmacists. This Act, introduced in 2010, commits to the establishment of a unified database to fulfil this intention. Both the public and medical community have received the legislation positively, though concerns about the ramifications of legal changes have been expressed. Because laws are largely provincially regulated, many speculate a national strategy is needed to prevent smuggling across provincial borders from jurisdictions with looser restrictions.[82][83][84] WP

In 2015, Purdue Pharma's abuse-resistant OxyNEO and six generic versions of OxyContin had been on the Canada-wide approved list for prescriptions since 2012. In June 2015, then-federal Minister of Health Rona Ambrose announced that within three years, all oxycodone products sold in Canada would need to be tamper-resistant. Some experts warned that the generic product manufacturers may not have the technology to achieve that goal, possibly giving Purdue Pharma a monopoly on this opiate.[85] WP

Several class-action suits across Canada have been launched against the Purdue group of companies and affiliates. Claimants argue the pharmaceutical manufacturers did not meet a standard of care and were negligent in doing so. These lawsuits reference earlier judgments in the United States, which held that Purdue was liable for wrongful marketing practices and misbranding. Since 2007, the Purdue companies have paid over CAN$650 million in settling litigation or facing criminal fines. WP

Germany

The drug is in Appendix III of the Narcotics Act (Betäubungsmittelgesetz or BtMG). The law allows only physicians, dentists, and veterinarians to prescribe oxycodone and the federal government to regulate the prescriptions (e.g., by requiring reporting).[86] WP

Hong kong

Oxycodone is regulated under Part I of Schedule 1 of Hong Kong's Chapter 134 Dangerous Drugs Ordinance.[87] WP

Japan

Oxycodone is a restricted drug in Japan. Its import and export are strictly restricted to specially designated organizations having a prior permit to import it. In a high-profile case an American who was a top Toyota executive living in Tokyo, who claimed to be unaware of the law, was arrested for importing oxycodone into Japan.[88][89] WP

Singapore

Oxycodone is listed as a Class A drug in the Misuse of Drugs Act of Singapore, which means offences concerning the drug attract the most severe level of punishment. A conviction for unauthorized manufacture of the drug attracts a minimum sentence of 10 years of imprisonment and corporal punishment of 5 strokes of the cane, and a maximum sentence of life imprisonment or 30 years of imprisonment and 15 strokes of the cane. The minimum and maximum penalties for unauthorized trafficking in the drug are respectively 5 years of imprisonment and 5 strokes of the cane, and 20 years of imprisonment and 15 strokes of the cane.[90][91] WP

United kingdom

Oxycodone is a Class A drug under the Misuse of Drugs Act 1971. For Class A drugs, which are "considered to be the most likely to cause harm", possession without a prescription is punishable by up to seven years in prison, an unlimited fine, or both. Dealing of the drug illegally is punishable by up to life imprisonment, an unlimited fine, or both. Oxycodone is a Schedule 2 drug under the Misuse of Drugs Regulations 2001 which "provide certain exemptions from the provisions of the Misuse of Drugs Act 1971".[92][93][94] WP

United states

Under the Controlled Substances Act, oxycodone is a Schedule II controlled substance whether by itself or part of a multi-ingredient medication. The Drug Enforcement Administration (DEA) lists oxycodone both for sale and for use in manufacturing other opioids as ACSCN 9143 and in 2013 approved the following annual aggregate manufacturing quotas: 131.5 metric tons for sale, down from 153.75 in 2012, and 10.25 metric tons for conversion, unchanged from the previous year. In 2020, oxycodone possession was decriminalized in the U.S. state of Oregon.[95][96][97] WP

Economics

The International Narcotics Control Board estimated 11.5 short tons of oxycodone were manufactured worldwide in 1998; by 2007 this figure had grown to 75.2 short tons. United States accounted for 82% of consumption in 2007 at 51.6 short tons. Canada, Germany, Australia, and France combined accounted for 13% of consumption in 2007. In 2010, 1.3 short tons of oxycodone were illegally manufactured using a fake pill imprint. This accounted for 0.8% of consumption. These illicit tablets were later seized by the U.S. Drug Enforcement Administration, according to the International Narcotics Control Board. The board also reported 122.5 short tons manufactured in 2010. This number had decreased from a record high of 135.9 short tons in 2009.[98–101] WP⚠ The source also gives this in other units.

Names

Expanded expressions for the compound oxycodone in the academic literature include "dihydrohydroxycodeinone", "Eucodal", "Eukodal", "14-hydroxydihydrocodeinone", and "Nucodan". In a UNESCO convention, the translations of "oxycodone" are oxycodon (Dutch), oxycodone (French), oxicodona (Spanish), الأوكسيكودون (Arabic), 羟考酮 (Chinese), and оксикодон (Russian).[3][31][102–105] WP

The word "oxycodone" should not be confused with "oxandrolone", "oxazepam", "oxybutynin", "oxytocin", or "Roxanol".[106] WP

Other brand names include Oxeltra, Longtec and Shortec.[107][108] WP

Pharmacology

Pharmacodynamics

Oxycodone, a semi-synthetic opioid, is a highly selective full agonist of the μ-opioid receptor (MOR). This is the main biological target of the endogenous opioid neuropeptide β-endorphin. Oxycodone has low affinity for the δ-opioid receptor (DOR) and the κ-opioid receptor (KOR), where it is an agonist similarly. After oxycodone binds to the MOR, a G protein-complex is released, which inhibits the release of neurotransmitters by the cell by decreasing the amount of cAMP produced, closing calcium channels, and opening potassium channels. Opioids like oxycodone are thought to produce their analgesic effects via activation of the MOR in the midbrain periaqueductal gray (PAG) and rostral ventromedial medulla (RVM). Conversely, they are thought to produce reward and addiction via activation of the MOR in the mesolimbic reward pathway, including in the ventral tegmental area, nucleus accumbens, and ventral pallidum. Tolerance to the analgesic and rewarding effects of opioids is complex and occurs due to receptor-level tolerance (e.g., MOR downregulation), cellular-level tolerance (e.g., cAMP upregulation), and system-level tolerance (e.g., neural adaptation due to induction of ΔFosB expression).[18][112–118] WP

Taken orally, 20 mg of immediate-release oxycodone is considered to be equivalent in analgesic effect to 30 mg of morphine, while extended release oxycodone is considered to be twice as potent as oral morphine.[119][120][121] WP

Similarly to most other opioids, oxycodone increases prolactin secretion, but its influence on testosterone levels is unknown. Unlike morphine, oxycodone lacks immunosuppressive activity (measured by natural killer cell activity and interleukin 2 production in vitro); the clinical relevance of this has not been clarified.[112] WP

Active metabolites

A few of the metabolites of oxycodone have also been found to be active as MOR agonists, some of which notably have much higher affinity for (as well as higher efficacy at) the MOR in comparison. Oxymorphone possesses 3- to 5-fold higher affinity for the MOR than does oxycodone, while noroxycodone and noroxymorphone possess one-third of and 3-fold higher affinity for the MOR, respectively, and MOR activation is 5- to 10-fold less with noroxycodone but 2-fold higher with noroxymorphone relative to oxycodone. Noroxycodone, noroxymorphone, and oxymorphone also have longer biological half-lives than oxycodone.[111][122–126] WP⚠ A table follows this text in the source and is not copied here. Open the source to see it.

However, despite the greater in vitro activity of some of its metabolites, it has been determined that oxycodone itself is responsible for 83.0% and 94.8% of its analgesic effect following oral and intravenous administration, respectively. Oxymorphone plays only a minor role, being responsible for 15.8% and 4.5% of the analgesic effect of oxycodone after oral and intravenous administration, respectively. Although the CYP2D6 genotype and the route of administration result in differential rates of oxymorphone formation, the unchanged parent compound remains the major contributor to the overall analgesic effect of oxycodone. In contrast to oxycodone and oxymorphone, noroxycodone and noroxymorphone, while also potent MOR agonists, poorly cross the blood–brain barrier into the central nervous system, and for this reason are only minimally analgesic in comparison.[111][122][123][124] WP

Κ-opioid receptor

In 1997, a group of Australian researchers proposed (based on a study in rats) that oxycodone acts on KORs, unlike morphine, which acts upon MORs. Further research by this group indicated the drug appears to be a high-affinity κ2b-opioid receptor agonist. However, this conclusion has been disputed, primarily on the basis that oxycodone produces effects that are typical of MOR agonists. In 2006, research by a Japanese group suggested the effect of oxycodone is mediated by different receptors in different situations. Specifically in diabetic mice, the KOR appears to be involved in the antinociceptive effects of oxycodone, while in nondiabetic mice, the μ₁-opioid receptor seems to be primarily responsible for these effects.[127–131] WP

Instant-release absorption profiles and tmax

Oxycodone can be administered orally, intravenously, via intravenous, intramuscular, or subcutaneous injection. Along with rectal, sublingual, buccal or intranasal drug delivery. The bioavailability of oral administration of oxycodone averages within a range of 60 to 87%, with rectal administration yielding the same results; Intranasal administration of oxycodone has a bioavailability of ~77%, the same half life as oral oxycodone, along with faster Tmax previously reported as 47% for nasal spray administration due to the solution in the study exceeding the 0.3- to 0.4-mL nasal mucosa limit. Buccal bioavailability ~55%, Tmax ~60 min. Sublingual bioavailability 20% (non alkalized) ~55% (alkalized) Tmax ~60 minutes.[132–135] WP

After a dose of conventional (immediate-release) oral oxycodone, the onset of action is 10 to 30 minutes, and peak plasma levels of the drug are attained within roughly 30 to 60 minutes; in contrast, after a dose of OxyContin (an oral controlled-release formulation), peak plasma levels of oxycodone occur in about three hours. Mean serum concentration of controlled-release oxycodone peaks at 78 ng/ml at 1 hour and drops to 20 ng/ml at 8 hours and under 10 ng/ml at 12 hours. The duration of instant-release oxycodone is 3 to 6 hours, although this can be variable depending on the individual.[68][122][125][136][137] WP

Distribution

Oxycodone has a volume of distribution of 2.6L/kg, in the blood it is distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and brain. At equilibrium the unbound concentration in the brain is threefold higher than the unbound concentration in blood. Conventional oral preparations start to reduce pain within 10 to 15 minutes on an empty stomach; in contrast, OxyContin starts to reduce pain within one hour.[15][137][138][139] WP

Metabolism

The metabolism of oxycodone in humans occurs in the liver mainly via the cytochrome P450 system and is extensive (about 95%) and complex, with many minor pathways and resulting metabolites. Around 10% (range 8–14%) of a dose of oxycodone is excreted essentially unchanged (unconjugated or conjugated) in the urine. The major metabolites of oxycodone are noroxycodone (70%), noroxymorphone ("relatively high concentrations"), and oxymorphone (5%). The immediate metabolism of oxycodone in humans is as follows:[110][111][122][125][140][141][142] WP

• N-Demethylation to noroxycodone predominantly via CYP3A4[110][111][122][125][140][141][142] WP
• O-Demethylation to oxymorphone predominantly via CYP2D6[110][111][122][125][140][141][142] WP
• 6-Ketoreduction to 6α- and 6β-oxycodol[110][111][122][125][140][141][142] WP
• N-Oxidation to oxycodone-N-oxide[110][111][122][125][140][141][142] WP

In humans, N-demethylation of oxycodone to noroxycodone by CYP3A4 is the major metabolic pathway, accounting for 45% ± 21% of a dose of oxycodone, while O-demethylation of oxycodone into oxymorphone by CYP2D6 and 6-ketoreduction of oxycodone into 6-oxycodols represent relatively minor metabolic pathways, accounting for 11% ± 6% and 8% ± 6% of a dose of oxycodone, respectively.[112][125] WP

Several of the immediate metabolites of oxycodone are subsequently conjugated with glucuronic acid and excreted in the urine. 6α-Oxycodol and 6β-oxycodol are further metabolized by N-demethylation to nor-6α-oxycodol and nor-6β-oxycodol, respectively, and by N-oxidation to 6α-oxycodol-N-oxide and 6β-oxycodol-N-oxide (which can subsequently be glucuronidated as well). Oxymorphone is also further metabolized, as follows:[125][141][142] WP

• 3-Glucuronidation to oxymorphone-3-glucuronide predominantly via UGT2B7[125][141][142] WP
• 6-Ketoreduction to 6α-oxymorphol and 6β-oxymorphol[125][141][142] WP
• N-Demethylation to noroxymorphone[125][141][142] WP

The first pathway of the above three accounts for 40% of the metabolism of oxymorphone, making oxymorphone-3-glucuronide the main metabolite of oxymorphone, while the latter two pathways account for less than 10% of the metabolism of oxymorphone. After N-demethylation of oxymorphone, noroxymorphone is further glucuronidated to noroxymorphone-3-glucuronide.[142] WP

Because oxycodone is metabolized by the cytochrome P450 system in the liver, its pharmacokinetics can be influenced by genetic polymorphisms and drug interactions concerning this system, as well as by liver function. Some people are fast metabolizers of oxycodone, while others are slow metabolizers, resulting in polymorphism-dependent alterations in relative analgesia and toxicity. While higher CYP2D6 activity increases the effects of oxycodone (owing to increased conversion into oxymorphone), higher CYP3A4 activity has the opposite effect and decreases the effects of oxycodone (owing to increased metabolism into noroxycodone and noroxymorphone). The dose of oxycodone must be reduced in patients with reduced liver function.[15][137][143][144][145] WP

Elimination

The clearance of oxycodone is 0.8 L/min. Oxycodone and its metabolites are mainly excreted in urine. Therefore, oxycodone accumulates in patients with kidney impairment. Oxycodone is eliminated in the urine 10% as unchanged oxycodone, 45% ± 21% as N-demethylated metabolites (noroxycodone, noroxymorphone, noroxycodols), 11 ± 6% as O-demethylated metabolites (oxymorphone, oxymorphols), and 8% ± 6% as 6-keto-reduced metabolites (oxycodols).[15][122][138][146] WP

Duration of action

Oral oxycodone has a half-life of 4.5 hours. The manufacturer of OxyContin (a controlled-release preparation of oxycodone), Purdue Pharma, claimed in its 1992 patent application that the duration of action of OxyContin is 12 hours in "90% of patients". Purdue has never performed any clinical studies in which OxyContin was given at more frequent intervals. In a separate filing, Purdue claimed that controlled-release oxycodone "provides pain relief in said patient for at least 12 hours after administration". However, in 2016, an investigation by the Los Angeles Times found that "the drug wears off hours early in many people", inducing symptoms of opiate withdrawal and intense cravings for OxyContin. One doctor, Lawrence Robbins, told journalists that over 70% of his patients would report that OxyContin would only provide 4–7 hours of relief. Doctors in the 1990s often would switch their patients to a dosing schedule of once every eight hours when patients complained that the duration of action for OxyContin was too short to be taken only twice a day.[138][147][148] WP

Purdue strongly discouraged the practice: Purdue's medical director Robert Reder wrote to one doctor in 1995 that "OxyContin has been developed for [12-hour] dosing...I request that you not use a [8-hourly] dosing regimen." Purdue repeatedly released memos to its sales representatives ordering them to remind doctors not to deviate from a 12-hour dosing schedule. One such memo read, "There is no Q8 dosing with OxyContin... [8-hour dosing] needs to be nipped in the bud. NOW!!" The journalists who covered the investigation argued that Purdue Pharma has insisted on a 12-hour duration of action for nearly all patients, despite evidence to the contrary, to protect the reputation of OxyContin as a 12-hour drug and the willingness of health insurance and managed care companies to cover OxyContin despite its high cost relative to generic opiates such as morphine.[147] WP

Purdue sales representatives were instructed to encourage doctors to write prescriptions for larger 12-hour doses instead of more frequent dosing. An August 1996 memo to Purdue sales representatives in Tennessee entitled "$$$$$$$$$$$$$ It's Bonus Time in the Neighborhood!" reminded the representatives that their commissions would dramatically increase if they were successful in convincing doctors to prescribe larger doses. Los Angeles Times journalists argue using interviews from opioid addiction experts that such high doses of OxyContin spaced 12 hours apart create a combination of agony during opiate withdrawal (lower lows) and a schedule of reinforcement that relieves this agony fostering addiction.[147][149] WP

As of 2026, the prescribing information for OxyContin still specifies a controversial 12-hour dosing schedule - which experts say promotes addiction - as the only option; it also still states, "there are no well-controlled clinical studies evaluating the safety and efficacy with dosing more frequently than every 12 hours."[71][150] WP

Detection in biological fluids

Oxycodone or its major metabolites may be measured in blood or urine to monitor for clearance, non-medical use, confirm a diagnosis of poisoning, or assist in a medicolegal death investigation. Many commercial opiate screening tests cross-react appreciably with oxycodone and its metabolites, but chromatographic techniques can easily distinguish oxycodone from other opiates.[151] WP

Receptor binding · Wikipedia

Oxycodone (and metabolite) at opioid receptors

Pharmacology of oxycodone and metabolites

Every row cites [110][111]

Chemistry

Formula

C18H21NO4 PC

CAS number

76-42-6 PC

Molar mass (g/mol)

315.4 PC

IUPAC name (computed by PubChem)

(4R,4aS,7aR,12bS)-4a-hydroxy-9-methoxy-3-methyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one PC

SMILES

CN1CC[C@]23[C@@H]4C(=O)CC[C@]2([C@H]1CC5=C3C(=C(C=C5)OC)O4)O PC

InChIKey

BRUQQQPBMZOVGD-XFKAJCMBSA-N PC

PubChem CID

5284603

Pop culture

No references added yet.

References

1. Other Publication of DE296916C
2. Other Sneader, W. Drug discovery: a history. 2005
3. Journal / agency Kalso, E. Oxycodone. Journal of Pain and Symptom Management. May 2005. doi:10.1016/j.jpainsymman.2005.01.010
4. Journal / agency Controlled-release oxycodone-induced seizures
5. Journal / agency Grapefruit juice enhances the exposure to oral oxycodone
6. Journal / agency Oxycodone/paracetamol: a low-dose synergic combination useful in different types of pain
7. Journal / agency Pharmacokinetics and pharmacodynamics of oxycodone when given intravenously and rectally to adult patients with cancer pain
8. Journal / agency Differential effects of food on the bioavailability of controlled-release oxycodone tablets and immediate-release oxycodone solution
9. Journal / agency Oxycodone is found to suppress sodium currents in the thalamic regions of the brain at high doses and is an effect that is independent of the MOR/u-opioid recepter and therefore this mechanism is not blocked by the use of naloxone
10. Other Oxycodone is found to have longer lasting more efficient effects on pain due to neuropathy because of having GABA-B agonist properties
11. Journal / agency Oxycodone when paired with an ultra low dose of naltrexone, an opioid antagonist, oxycodone has a longer duration of pain relief
12. Other Oxycodone has been found to be an effective treatment for restless leg syndrome
13. Journal / agency Pharmacokinetics of oxycodone done orally and intramuscularly
14. Journal / agency Remillard D, Kaye AD, McAnally H. Oxycodone's Unparalleled Addictive Potential: Is it Time for a Moratorium?. Current Pain and Headache Reports. February 2019. doi:10.1007/s11916-019-0751-7 · PMID 30820686
15. Other Oxycodone Monograph for Professionals
16. Journal / agency Pergolizzi JV, Taylor R, LeQuang JA, Raffa RB. Managing severe pain and abuse potential: the potential impact of a new abuse-deterrent formulation oxycodone/naltrexone extended-release product. Journal of Pain Research. 2018. doi:10.2147/JPR.S127602 · PMID 29445297 · PMC5810535
17. Other British national formulary: BNF 74. 2017
18. Other Talley NJ, Frankum B, Currow D. Essentials of Internal Medicine 3e. 10 February 2015
19. Other Opioid Conversion / Equivalency Table. 20 April 2013
20. Other Top 300 of 2023
21. Other Oxycodone Drug Usage Statistics, United States, 2014 - 2023
22. Journal / agency Dart RC, Iwanicki JL, Dasgupta N, Cicero TJ, Schnoll SH. Do abuse deterrent opioid formulations work?. Journal of Opioid Management. 2017. doi:10.5055/jom.2017.0415 · PMID 29308584
23. Journal / agency https://pmc.ncbi.nlm.nih.gov/articles/PMC6602093/
24. Journal / agency https://pmc.ncbi.nlm.nih.gov/articles/PMC4006196/#S9
25. Other Why Heroin Relapse Often Ends In Death - Lauren F Friedman (Business Insider)
26. Journal / agency Siegel, S., Hinson, R. E., Krank, M. D., McCully, J. Heroin “Overdose” Death: Contribution of Drug-Associated Environmental Cues. Science. 23 April 1982. doi:10.1126/science.7200260
27. Journal / agency Freund M, Speyer E. Über die Umwandlung von Thebain in Oxycodeinon und dessen Derivate. Journal für Praktische Chemie. 24 November 1916. doi:10.1002/prac.19160940112
28. Other Sneader W. Drug discovery: a history. 2005
29. Journal / agency Martin Freund. Berichte der Deutschen Chemischen Gesellschaft (A and B Series). 7 May 1921. doi:10.1002/cber.19210540533
30. Other The Holocaust: a history of the Jews of Europe during the Second World War. 1986
31. Journal / agency Sunshine A, Olson NZ, Colon A, Rivera J, Kaiko RF, Fitzmartin RD, Reder RF, Goldenheim PD. Analgesic efficacy of controlled-release oxycodone in postoperative pain. Journal of Clinical Pharmacology. July 1996. doi:10.1002/j.1552-4604.1996.tb04223.x · PMID 8844441
32. Journal / agency Defalque RJ, Wright AJ. Scophedal (SEE) was it a fad or a miracle drug?. Bulletin of Anesthesia History. October 2003. doi:10.1016/S1522-8649(03)50051-8 · PMID 17494237
33. Other William S Burroughs 1952 letter to Allen Ginsburg concerning Eukodal, in Collected Correspondance, pp 141–2
34. Other Merck 1930 package insert for Skophedal (German)
35. Other Breitenbach D. A fresh light on the Nazis' wartime drug addiction. 9 September 2015
36. Other Ohler N, Whiteside S. Blitzed: drugs in the Third Reich. 2017
37. Other codified at et. seq USStatute 91 513 84 1236 1970 10 27
38. Journal / agency Sapienza FL. Abuse deterrent formulations and the Controlled Substances Act (CSA). Drug and Alcohol Dependence. June 2006. doi:10.1016/j.drugalcdep.2005.11.028 · PMID 16529882
39. Other Keefe PR. The Family That Built an Empire of Pain. 23 October 2017
40. Other Confirmation Hearing for FDA Commissioner Nominee. 14 December 2021
41. Other Mitchell J. How the FDA helped pave the way for an opioid epidemic. 26 January 2018
42. Other OxyContin: Pain Relief vs. Abuse
43. Journal / agency Opioid overdose
44. Journal / agency WHO Expert Committee on Drug Dependence: forty-third report
45. Other Girioin L, Haely M. FDA to require stricter labeling for pain drugs. 11 September 2013
46. Other Now a counselor, she went from stoned to straight, San Francisco Chronicle, 2 November. 2015
47. Other Overdose Death Rates. 29 January 2019
48. Other Oxycontin and Addiction
49. Journal / agency Policy Impact: Prescription Pain Killer Overdoses Centers for Disease Control and Prevention. Retrieved 24 December 2013
50. Journal / agency ER/LA Opioid Analgesic Class Labeling Changes and Postmarket Requirements
51. Other Reformulated OxyContin reduces abuse but many addicts have switched to heroin, The Pharmaceutical Journal, 16 March 2015. link 2
52. Other Meier B. Sackler Scion's Email Reveals Push for High-Dose OxyContin, New Lawsuit Disclosures Claim. 31 January 2019
53. Other Bebinger M, Willmsen C. Mass. AG Implicates Family Behind Purdue Pharma In Opioid Deaths. 15 January 2019
54. Other DeCosta-Klipa N. Maura Healey explains why she refused to join the Purdue Pharma settlement. 17 September 2019
55. Other Black E. Australian drug trends 2007. Findings from the Illicit Drug Reporting System (IDRS). 2008
56. Other Boyle T. Opioid deaths soaring, study finds Opioid-related deaths in Ontario jumped by a whopping 242 per cent over two decades, according to a study by ICES and St. Mike's. 7 July 2014
57. Other Donovan K. Oxycodone found to be more deadly than heroin. 10 February 2009
58. Other Study finds huge rise in oxycodone deaths
59. Other OxyContin Fact Sheet
60. Other Health Canada – Misuse and Abuse of Oxycodone-based Prescription Drugs. 11 January 2010
61. Other Kirkey S. OxyNEO another prescription for disaster?. 23 May 2012
62. Other Criger E. Death of OxyContin behind rise of fentanyl?. 17 August 2015
63. Other Gatehouse J, Macdonald N. Fentanyl: The King of all Opiates, and a Killer Drug Crisis. 22 June 2015
64. Other Southwick R. Fentanyl brings tragedy to Blood Tribe. 2 December 2015
65. Other Police believe organized crime is flooding the Blood Tribe reserve with an illegal drug that has been linked to 10 deaths. 23 January 2015
66. Other Gordon T. Huge rise in Scots misuse of painkiller. 30 March 2008
67. Other Thompson T. Epidemic fear as 'hillbilly heroin' hits the streets. 24 March 2002
68. Other New Abuse Deterrent Formulation Technology for Immediate-Release Opioids. 2010
69. Other Diep F. How Do You Make a Painkiller Addiction-Proof. 13 May 2013
70. Other Coplan P. Findings from Purdue's Post-Marketing Epidemiology Studies of Reformulated OxyContin's Effects. 2012
71. Journal / agency Oxycontin- oxycodone hydrochloride tablet, film coated, extended release. 5 December 2024
72. Other Oxycontin (Oxycodone HCl): Side Effects, Uses, Dosage, Interactions, Warnings
73. Journal / agency FDA approves abuse-deterrent labeling for reformulated OxyContin
74. Other Pfizer and Acura Announce FDA Approval of Oxectatm (Oxycodone HCL, USP) CII
75. Other Fiore K. FDA Okays New Abuse-Resistant Opioid. 20 June 2011
76. Other League of Nations. Convention for limiting the manufacture and regulating the distribution of narcotic drugs. 1931
77. Other United Nations conference for the adoption of a single convention on narcotic drugs. Final act. 1961
78. Other Commonwealth of Australia. Narcotic Drugs Act 1967 – first schedule
79. Other Australian Government. Department of Health and Aging. Therapeutic Goods Administration. Standard for the uniform scheduling of drugs and poisons no. 23. June 2008
80. Other Canada Department of Justice. Controlled Drugs and Substances Act (1996, c. 19). 27 February 2009
81. Other Olgilvie, Megan. "Ontario delisting OxyContin and its substitute from drug benefit program" Toronto Star (17 February 2012). link 2
82. Other Narcotics Safety and Awareness Act. 2010. Ministry of Health and Long Term Care. link 2
83. Other Dhalla I, Born K. Opioids. 22 February 2012
84. Other Ontario OxyContin Rules: New Restrictions Applauded But National Rules Needed. 20 February 2012
85. Other Weeks C, Howlett K. New oxycodone rules would give drug maker a monopoly in Canada, experts warn. 4 August 2015
86. Other German Federal Ministry of Justice. Act on the circulation of narcotics (Narcotics Act – BtMG). 19 January 2009
87. Other Hong Kong Special Administrative Region, People's Republic of China. Dangerous drugs ordinance – chapter 134
88. Other Toyota's American PR chief arrested for suspected drug violation. 19 June 2015
89. Other Toyota: American exec did not intend to break Japan law
90. Other (Singapore), section 6(1) Singapore legislation
91. Other Misuse of Drugs Act (Singapore), section 5(1)
92. Other List of drugs currently controlled under the Misuse of Drugs legislation. 2009
93. Other Class A, B and C drugs
94. Other Statutory instrument 2001 No. 3998. The Misuse of Drugs regulations 2001
95. Other DEA. Controlled substance scheduling
96. Other DEA Diversion Control CSA
97. Other Selsky A. Oregon leads the way in decriminalizing hard drugs. 4 November 2020
98. Other International Narcotics Control Board. Narcotic drugs: estimated world requirements for 2009; statistics for 2007. Report E/INCB/2008/2. 2009
99. Other Availability of Opioid Analgesics in the World and Asia, With a special focus on: Indonesia, Philippines, Thailand
100. Other International Narcotics Control Board. Narcotic Drugs: Estimated World Requirements for 2012 and Statistics for 2010. 2011
101. Other Narcotic Drugs: Estimated World Requirements for 2012 and Statistics for 2010. International Narcotics Control Board (2011). link 2
102. Other The Merck index. 2006
103. Other Eddy NB. The National Research Council involvement in the opiate problem, 1928–1971. 1973
104. Journal / agency May EL, Jacobson AE. The Committee on Problems of Drug Dependence: a legacy of the National Academy of Sciences. A historical account. Drug and Alcohol Dependence. June 1989. doi:10.1016/0376-8716(89)90083-5 · PMID 2666074
105. Other United Nations Educational, Scientific; Cultural Organization. International convention against doping in sport. 2005
106. Other MEDMARX data report. A report on the relationship of drug names and medication errors in response to the Institute of Medicine's call for action. 2008
107. Other Oxeltra 5 mg Prolonged-Release Tablets - Summary of Product Characteristics (SmPC) - (emc) | 1902
108. Other Postlethwaite J. Oxycodone Longtec Patient Leaflet
109. Journal / agency Corbett AD, Paterson SJ, Kosterlitz HW. Opioids. 1993. doi:10.1007/978-3-642-77460-7_26
110. Other Fitzgibbon DR, Loeser JD. Cancer Pain. 28 March 2012
111. Other Preedy VR. Neuropathology of Drug Addictions and Substance Misuse Volume 3: General Processes and Mechanisms, Prescription Medications, Caffeine and Areca, Polydrug Misuse, Emerging Addictions and Non-Drug Addictions. 25 April 2016
112. Other Davis MP. Opioids in Cancer Pain. 28 May 2009
113. Other Forbes K. Opioids in Cancer Pain. 29 November 2007
114. Journal / agency Chahl L. Opioids- mechanism of action. Aust Prescr. 1996. doi:10.18773/austprescr.1996.063
115. Other Stein C. Opioids in Pain Control: Basic and Clinical Aspects. 1999
116. Other Squire L, Berg D, Bloom FE, du Lac S, Ghosh A, Spitzer NC. Fundamental Neuroscience. 17 December 2012
117. Other Kringelbach ML, Berridge KC. Pleasures of the Brain. 2010
118. Other Sinatra RS, Jahr JS, Watkins-Pitchford JM. The Essence of Analgesia and Analgesics. 14 October 2010
119. Other Treatment of Pain
120. Other Ferrell BR, Pasero C, McCaffery M. Pain Assessment and Pharmacologic Management. 2010
121. Other Levy EF, Victor J. Opioids in medicine a comprehensive review on the mode of action and the use of analgesics in different clinical pain states. 2007
122. Journal / agency Lalovic B, Kharasch E, Hoffer C, Risler L, Liu-Chen LY, Shen DD. Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: role of circulating active metabolites. Clinical Pharmacology and Therapeutics. May 2006. doi:10.1016/j.clpt.2006.01.009 · PMID 16678548
123. Journal / agency Klimas R, Witticke D, El Fallah S, Mikus G. Contribution of oxycodone and its metabolites to the overall analgesic effect after oxycodone administration. Expert Opinion on Drug Metabolism & Toxicology. May 2013. doi:10.1517/17425255.2013.779669 · PMID 23488585
124. Journal / agency Lemberg KK, Siiskonen AO, Kontinen VK, Yli-Kauhaluoma JT, Kalso EA. Pharmacological characterization of noroxymorphone as a new opioid for spinal analgesia. Anesthesia and Analgesia. February 2008. doi:10.1213/ane.0b013e3181605a15 · PMID 18227301
125. Other Smith H, Passik S. Pain and Chemical Dependency. 25 April 2008
126. Other Firestein GS, Budd RC, Gabriel SE, McInnes IB, O'Dell JR. Kelley and Firestein's Textbook of Rheumatology. 21 June 2016
127. Journal / agency Ross FB, Smith MT. The intrinsic antinociceptive effects of oxycodone appear to be kappa-opioid receptor mediated. Pain. November 1997. doi:10.1016/S0304-3959(97)00093-6 · PMID 9415500
128. Journal / agency Smith MT. Differences between and combinations of opioids re-visited. Current Opinion in Anesthesiology. October 2008. doi:10.1097/ACO.0b013e32830a4c4a · PMID 18784485
129. Journal / agency Kalso E. How different is oxycodone from morphine?. Pain. December 2007. doi:10.1016/j.pain.2007.09.027 · PMID 17961923
130. Journal / agency Nozaki C, Saitoh A, Kamei J. Characterization of the antinociceptive effects of oxycodone in diabetic mice. European Journal of Pharmacology. March 2006. doi:10.1016/j.ejphar.2006.02.002 · PMID 16533506
131. Journal / agency Nozaki C, Kamei J. Involvement of mu1-opioid receptor on oxycodone-induced antinociception in diabetic mice. European Journal of Pharmacology. April 2007. doi:10.1016/j.ejphar.2007.01.021 · PMID 17292346
132. Journal / agency Lofwall MR, Moody DE, Fang WB, Nuzzo PA, Walsh SL. Pharmacokinetics of intranasal crushed OxyContin and intravenous oxycodone in nondependent prescription opioid abusers. Journal of Clinical Pharmacology. April 2012. doi:10.1177/0091270011401620 · PMID 21610203 · PMC4006196
133. Other Analgesic Expert Group. Therapeutic Guidelines: Analgesic. Version 4. Melbourne: Therapeutic Guidelines Ltd, 2007
134. Journal / agency Kinnunen M, Piirainen P, Kokki H, Lammi P, Kokki M. Updated Clinical Pharmacokinetics and Pharmacodynamics of Oxycodone. Clinical Pharmacokinetics. June 2019. doi:10.1007/s40262-018-00731-3 · PMID 30652261
135. Journal / agency Li Y, Sun D, Palmisano M, Zhou S. Slow drug delivery decreased total body clearance and altered bioavailability of immediate- and controlled-release oxycodone formulations. Pharmacology Research & Perspectives. February 2016. doi:10.1002/prp2.210 · PMID 26977300 · PMC4777261
136. Other Elliott JA, Smith HS. Handbook of Acute Pain Management. 19 April 2016
137. Other 1. Package insert Oxycontin. 5 November 2007
138. Harm reduction site Oxycodone
139. Journal / agency Boström E, Simonsson US, Hammarlund-Udenaes M. In vivo blood-brain barrier transport of oxycodone in the rat: indications for active influx and implications for pharmacokinetics/pharmacodynamics. Drug Metabolism and Disposition. September 2006. doi:10.1124/dmd.106.009746 · PMID 16763013
140. Journal / agency Moore KA, Ramcharitar V, Levine B, Fowler D. Tentative identification of novel oxycodone metabolites in human urine. Journal of Analytical Toxicology. September 2003. doi:10.1093/jat/27.6.346 · PMID 14516487
141. Other McPherson RA, Pincus MR. Henry's Clinical Diagnosis and Management by Laboratory Methods. 31 March 2016
142. Other Anzenbacher P, Zanger UM. Metabolism of Drugs and Other Xenobiotics. 29 May 2012
143. Journal / agency Gasche Y, Daali Y, Fathi M, Chiappe A, Cottini S, Dayer P, Desmeules J. Codeine intoxication associated with ultrarapid CYP2D6 metabolism. The New England Journal of Medicine. December 2004. doi:10.1056/NEJMoa041888 · PMID 15625333
144. Journal / agency Otton SV, Wu D, Joffe RT, Cheung SW, Sellers EM. Inhibition by fluoxetine of cytochrome P450 2D6 activity. Clinical Pharmacology and Therapeutics. April 1993. doi:10.1038/clpt.1993.43 · PMID 8477556
145. Journal / agency Samer CF, Daali Y, Wagner M, Hopfgartner G, Eap CB, Rebsamen MC, Rossier MF, Hochstrasser D, Dayer P, Desmeules JA. Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety. British Journal of Pharmacology. June 2010. doi:10.1111/j.1476-5381.2010.00709.x · PMID 20590588 · PMC2935998
146. Other Davis PJ, Cladis FP. Smith's Anesthesia for Infants and Children E-Book. 15 October 2016
147. Other Ryan H, Girion L, Glover S. You want a description of hell?' OxyContin's 12-hour problem. 7 July 2016
148. Other 'Q12' Workshops, 2001
149. Other Abramson, John. Sickening: How Big Pharma Broke American Health Care and How We Can Repair It. 2022
150. Other OxyContin Investigation
151. Other Baselt R. Disposition of Toxic Drugs and Chemicals in Man. 2017

Text and values on this page are quoted from PsychonautWiki (CC BY-SA 4.0), Wikipedia (CC BY-SA 4.0), TripSit factsheets, PubChem (public domain). Each value links to the exact revision it came from.