Editing Oxycodone (section)

====Active metabolites====
A few of the [[metabolite]]s of oxycodone have also been found to be active as MOR agonists, some of which notably have much higher [[affinity (pharmacology)|affinity]] for (as well as higher [[intrinsic activity|efficacy]] at) the MOR in comparison.<ref name="LalovicKharasch2006">{{cite journal | vauthors = Lalovic B, Kharasch E, Hoffer C, Risler L, Liu-Chen LY, Shen DD | title = Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: role of circulating active metabolites | journal = Clinical Pharmacology and Therapeutics | volume = 79 | issue = 5 | pages = 461–479 | date = May 2006 | pmid = 16678548 | doi = 10.1016/j.clpt.2006.01.009 | s2cid = 21372271 }}</ref><ref name="KlimasWitticke2013">{{cite journal | vauthors = Klimas R, Witticke D, El Fallah S, Mikus G | title = Contribution of oxycodone and its metabolites to the overall analgesic effect after oxycodone administration | journal = Expert Opinion on Drug Metabolism & Toxicology | volume = 9 | issue = 5 | pages = 517–528 | date = May 2013 | pmid = 23488585 | doi = 10.1517/17425255.2013.779669 | s2cid = 22857902 }}</ref><ref name="LembergSiiskonen2008">{{cite journal | vauthors = Lemberg KK, Siiskonen AO, Kontinen VK, Yli-Kauhaluoma JT, Kalso EA | title = Pharmacological characterization of noroxymorphone as a new opioid for spinal analgesia | journal = Anesthesia and Analgesia | volume = 106 | issue = 2 | pages = 463–70, table of contents | date = February 2008 | pmid = 18227301 | doi = 10.1213/ane.0b013e3181605a15 | s2cid = 16524280 | doi-access = free }}</ref> [[Oxymorphone]] possesses 3- to 5-fold higher affinity for the MOR than does oxycodone,<ref name="SmithPassik2008">{{cite book |vauthors=Smith H, Passik S |title=Pain and Chemical Dependency |url=https://books.google.com/books?id=T88C-9VTDXMC&pg=PA195 |date=25 April 2008 |publisher=Oxford University Press USA |isbn=978-0-19-530055-0 |pages=195– |access-date=5 October 2016 |archive-date=7 October 2022 |archive-url=https://web.archive.org/web/20221007000913/https://books.google.com/books?id=T88C-9VTDXMC&pg=PA195 |url-status=live }}</ref> while [[noroxycodone]] and [[noroxymorphone]] possess one-third of and 3-fold higher affinity for the MOR, respectively,<ref name="SmithPassik2008"/><ref name="LembergSiiskonen2008" /> and MOR activation is 5- to 10-fold less with noroxycodone but 2-fold higher with noroxymorphone relative to oxycodone.<ref name="Preedy2016" /> Noroxycodone, noroxymorphone, and oxymorphone also have longer [[biological half-life|biological half-lives]] than oxycodone.<ref name="LalovicKharasch2006" /><ref name="FiresteinBudd2016">{{cite book |vauthors=Firestein GS, Budd RC, Gabriel SE, McInnes IB, O'Dell JR |title=Kelley and Firestein's Textbook of Rheumatology |url=https://books.google.com/books?id=kBZ6DAAAQBAJ&pg=PA1080 |date=21 June 2016 |publisher=Elsevier Health Sciences |isbn=978-0-323-31696-5 |lccn=2016009254 |pages=1080– |access-date=5 October 2016 |archive-date=7 October 2022 |archive-url=https://web.archive.org/web/20221007000913/https://books.google.com/books?id=kBZ6DAAAQBAJ&pg=PA1080 |url-status=live }}</ref>

{| class="wikitable"
|+ Pharmacology of oxycodone and metabolites<ref name="FitzgibbonLoeser2012" /><ref name="Preedy2016" />
|-
! Compound !! {{abbrlink|K<sub>i</sub>|Inhibitor constant}} !! {{abbrlink|EC<sub>50</sub>|Half-maximal effective concentration}} !! [[Cmax (pharmacology)|{{abbr|C<sub>max</sub>|Peak serum concentrations}}]] !! [[Area under the curve (pharmacokinetics)|{{abbr|AUC|Area under the curve}}]]
|-
| Oxycodone || 16.0 nM || 343 nM || 23.2 ± 8.6&nbsp;ng/mL || 236 ± 102&nbsp;ng/h/mL
|-
| [[Oxymorphone]] || 0.36 nM || 42.8 nM || 0.82 ± 0.85&nbsp;ng/mL || 12.3 ± 12&nbsp;ng/h/mL
|-
| [[Noroxycodone]] || 57.1 nM || 1930 nM || 15.2 ± 4.5&nbsp;ng/mL || 233 ± 102&nbsp;ng/h/mL
|-
| [[Noroxymorphone]] || 5.69 nM || 167 nM || {{abbr|ND|No data}} || {{abbr|ND|No data}}
|- class="sortbottom"
| colspan="5" style="width: 1px;" |{{Small|K<sub>i</sub> is for [<sup>3</sup>H]diprenorphine displacement. (Note that diprenorphine is a non-selective opioid receptor ligand, so this is not MOR-specific.) EC<sub>50</sub> is for hMOR1 GTPyS binding. C<sub>max</sub> and AUC levels are for 20&nbsp;mg CR oxycodone.}}
|}

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.<ref name="KlimasWitticke2013" /> 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.<ref name="KlimasWitticke2013" /> 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.<ref name="KlimasWitticke2013" /> 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.<ref name="LalovicKharasch2006" /><ref name="Preedy2016" /><ref name="KlimasWitticke2013" /><ref name="LembergSiiskonen2008" />