Editing Morphine (section)

=== Pharmacokinetics ===
==== Absorption and metabolism ====
Morphine can be taken [[oral administration|orally]], [[Sublingual administration|sublingually]], [[Buccal space|bucally]], [[rectal administration|rectally]], [[subcutaneous injection|subcutaneously]], [[Insufflation (medicine)|intranasally]], [[intravenous]]ly, [[intrathecal]]ly or [[epidural]]ly and inhaled via a nebulizer. As a recreational drug, it is becoming more common to inhale ("[[Chasing the Dragon]]"), but, for medical purposes, intravenous (IV) injection is the most common method of administration. Morphine is subject to extensive [[first-pass metabolism]] (a large proportion is broken down in the liver), so, if taken orally, only 40% to 50% of the dose reaches the central nervous system. Resultant plasma levels after subcutaneous (SC), intramuscular (IM), and IV injection are all comparable. After IM or SC injections, morphine plasma levels peak in approximately 20&nbsp;min, and, after oral administration, levels peak in approximately 30&nbsp;min.<ref>{{cite journal | vauthors = Trescot AM, Datta S, Lee M, Hansen H | title = Opioid pharmacology | journal = Pain Physician | volume = 11 | issue = 2 Suppl | pages = S133-53 | date = March 2008 | doi = 10.36076/ppj.2008/11/S133 | pmid = 18443637 }}</ref> Morphine is [[metabolised]] primarily in the [[liver]] and approximately 87% of a dose of morphine is excreted in the [[urine]] within 72&nbsp;h of administration. Morphine is metabolized primarily into [[morphine-3-glucuronide]] (M3G) and [[morphine-6-glucuronide]] (M6G)<ref name="Kilpatrick_2005">{{cite journal | vauthors = Kilpatrick GJ, Smith TW | title = Morphine-6-glucuronide: actions and mechanisms | journal = Medicinal Research Reviews | volume = 25 | issue = 5 | pages = 521–44 | date = September 2005 | pmid = 15952175 | doi = 10.1002/med.20035 | s2cid = 20887610 }}</ref> via [[glucuronidation]] by phase II metabolism enzyme [[UGT2B7|UDP-glucuronosyl transferase-2B7]] (UGT2B7). About 60% of morphine is converted to M3G, and 6% to 10% is converted to M6G.<ref name="van Dorp" /> Not only does the metabolism occur in the liver but it may also take place in the brain and the kidneys. M3G does not undergo opioid receptor binding and has no analgesic effect. M6G binds to μ-receptors and is half as potent an analgesic as morphine in humans.<ref name="van Dorp">{{cite journal | vauthors = van Dorp EL, Romberg R, Sarton E, Bovill JG, Dahan A | title = Morphine-6-glucuronide: morphine's successor for postoperative pain relief? | journal = Anesthesia and Analgesia | volume = 102 | issue = 6 | pages = 1789–97 | date = June 2006 | pmid = 16717327 | doi = 10.1213/01.ane.0000217197.96784.c3 | s2cid = 18890026 | url = http://www.anesthesia-analgesia.org/cgi/content/full/102/6/1789 | url-status = live | archive-url = https://web.archive.org/web/20081201234703/http://www.anesthesia-analgesia.org/cgi/content/full/102/6/1789 | archive-date = 1 December 2008 | doi-access = free }}</ref> Morphine may also be metabolized into small amounts of [[normorphine]], [[codeine]], and [[hydromorphone]]. Metabolism rate is determined by gender, age, diet, genetic makeup, disease state (if any), and use of other medications. The elimination [[half-life]] of morphine is approximately 120&nbsp;min, though there may be slight differences between men and women. Morphine can be stored in fat, and, thus, can be detectable even after death. Morphine can cross the [[blood–brain barrier]], but, because of poor lipid solubility, protein binding, rapid conjugation with glucuronic acid, and ionization, it does not cross easily. [[Heroin]], which is derived from morphine, crosses the blood-brain barrier more easily, making it more potent.<ref name="Jenkins AJ 2008">Jenkins AJ (2008) Pharmacokinetics of specific drugs. In Karch SB (''Ed''), ''Pharmacokinetics and pharmacodynamics of abused drugs''. CRC Press: Boca Raton.</ref>

==== Extended-release ====
{{Main|Extended-release morphine}}
There are [[Time release technology|extended-release]] formulations of orally administered morphine whose effect lasts longer, which can be given once per day. Brand names for this formulation of morphine include Avinza,<ref name=maryland /> Kadian,<ref name=maryland /> MS Contin,<ref name=maryland>{{cite web |url = https://umm.edu/health/medical/drug-notes/notes/morphine-slow-release-by-mouth |title = Morphine, slow release (By mouth) |website = [[University of Maryland Medical Center]] |url-status = live |archive-url = https://web.archive.org/web/20151222173053/https://umm.edu/health/medical/drug-notes/notes/morphine-slow-release-by-mouth |archive-date = 22 December 2015 }}</ref> Dolcontin, and DepoDur.<ref name="PedersenFredheim2015">{{cite journal | vauthors = Pedersen L, Fredheim O | title = Opioids for chronic noncancer pain: still no evidence for superiority of sustained-release opioids | journal = Clinical Pharmacology and Therapeutics | volume = 97 | issue = 2 | pages = 114–5 | date = February 2015 | pmid = 25670511 | doi = 10.1002/cpt.26 | s2cid = 5603973 }} Last reviewed on 18 November 2015</ref> For constant pain, the relieving effect of extended-release morphine given once (for Kadian)<ref name=medscape>{{cite web |url = http://reference.medscape.com/drug/ms-contin-astramorph-morphine-343319 |title = Dosing & Uses |website = [[Medscape]] |access-date = 21 December 2015 |url-status = live |archive-url = https://web.archive.org/web/20151031152616/http://reference.medscape.com/drug/ms-contin-astramorph-morphine-343319 |archive-date = 31 October 2015 }}</ref> or twice (for MS Contin)<ref name=medscape /> every 24 hours is roughly the same as multiple administrations of ''immediate release'' (or "regular") morphine.<ref name=northwestern>{{cite web |url = http://endoflife.northwestern.edu/pain_management/morphine.pdf |title = EndLink: An Internet-based End of Life Care Education Program – Morphine Dosing |website = [[Northwestern University]] |url-status = live |archive-url = https://web.archive.org/web/20160304092914/http://endoflife.northwestern.edu/pain_management/morphine.pdf |archive-date = 4 March 2016 }}</ref> Extended-release morphine can be administered together with "rescue doses" of immediate-release morphine as needed in case of breakthrough pain, each generally consisting of 5% to 15% of the 24-hour extended-release dosage.<ref name=northwestern />

==== Detection in body fluids ====
Morphine and its major metabolites, morphine-3-glucuronide, and morphine-6-glucuronide, can be detected in blood, plasma, hair, and urine using an [[immunoassay]]. [[Chromatography]] can be used to test for each of these substances individually. Some testing procedures [[hydrolysis|hydrolyze]] metabolic products into morphine before the immunoassay, which must be considered when comparing morphine levels in separately published results. Morphine can also be isolated from whole blood samples by [[solid phase extraction]] (SPE) and detected using [[liquid chromatography-mass spectrometry]] (LC-MS).

Ingestion of codeine or food containing poppy seeds can cause false positives.<ref>{{cite book | vauthors = Baselt RC |title = Disposition of Toxic Drugs and Chemicals in Man |year = 2008 |edition = 8th |publisher = Biomedical Publications |location = Foster City, CA |isbn = 978-0-9626523-7-0 |pages = 1057–1062 }}</ref>

A 1999 review estimated that relatively low doses of heroin (which metabolizes immediately into morphine) are detectable by standard urine tests for 1–1.5 days after use.<ref name="pmid11484423">{{cite journal | vauthors = Vandevenne M, Vandenbussche H, Verstraete A | title = Detection time of drugs of abuse in urine | journal = Acta Clinica Belgica | volume = 55 | issue = 6 | pages = 323–33 | year = 2000 | pmid = 11484423 | doi = 10.1080/17843286.2000.11754319 | s2cid = 43808583 }}</ref> A 2009 review determined that, when the [[analyte]] is morphine and the [[limit of detection]] is 1{{space}}ng/ml, a 20{{space}}mg intravenous (IV) dose of morphine is detectable for 12–24 hours. A limit of detection of 0.6{{space}}ng/ml had similar results.<ref name="pmid15228165">{{cite journal | vauthors = Verstraete AG | title = Detection times of drugs of abuse in blood, urine, and oral fluid | journal = Therapeutic Drug Monitoring | volume = 26 | issue = 2 | pages = 200–5 | date = April 2004 | pmid = 15228165 | doi = 10.1097/00007691-200404000-00020 | s2cid = 385874 }}</ref>