Editing Nicotine (section)

===Pharmacokinetics===
[[File:Nicotine metabolism.png|thumb|upright=1.5|600px|class=skin-invert-image|Urinary metabolites of nicotine, quantified as average percentage of total urinary nicotine<ref>{{cite book| vauthors = Henningfield JE, Calvento E, Pogun S  |title=Nicotine Psychopharmacology |series=Handbook of Experimental Pharmacology |date=2009 |volume=192 |publisher=Springer|isbn=978-3-540-69248-5|pages=35, 37 |doi=10.1007/978-3-540-69248-5 }}</ref>]]
<!--Summarize this: "Nicotine undergoes first-pass metabolism in the liver, reducing the overall bioavailability of swallowed nicotine pills. A pill that could reliably produce high enough nicotine levels in the central nervous system would risk causing adverse gastrointestinal effects. To avoid this problem, nicotine replacement products are formulated for absorption through the oral or nasal mucosa (chewing gum, lozenges, sublingual tablets, inhalator, spray) or through the skin (transdermal patches)."<ref name="Cochrane NRT 2018" /> -->
As nicotine enters the body, it is distributed quickly through the [[blood]]stream and crosses the [[blood–brain barrier]] reaching the [[human brain|brain]] within 10–20 seconds after inhalation.<ref name="pmid12971663">{{cite journal | vauthors = Le Houezec J | title = Role of nicotine pharmacokinetics in nicotine addiction and nicotine replacement therapy: a review | journal = The International Journal of Tuberculosis and Lung Disease | volume = 7 | issue = 9 | pages = 811–9 | date = September 2003 | pmid = 12971663 }}</ref> The [[elimination half-life]] of nicotine in the body is around two hours.<ref>{{cite journal | vauthors = Kolli AR, Calvino-Martin F, Kuczaj AK, Wong ET, Titz B, Xiang Y, Lebrun S, Schlage WK, Vanscheeuwijck P, Hoeng J | title = Deconvolution of Systemic Pharmacokinetics Predicts Inhaled Aerosol Dosimetry of Nicotine | journal = European Journal of Pharmaceutical Sciences | volume = 180 | pages = 106321 | date = January 2023 | pmid = 36336278 | doi = 10.1016/j.ejps.2022.106321 | doi-access = free }}</ref><ref name="pmid7077531">{{cite journal | vauthors = Benowitz NL, Jacob P, Jones RT, Rosenberg J | title = Interindividual variability in the metabolism and cardiovascular effects of nicotine in man | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 221 | issue = 2 | pages = 368–72 | date = May 1982 | doi = 10.1016/S0022-3565(25)33068-5 | pmid = 7077531 }}</ref> Nicotine is primarily [[Excretion|excreted]] in [[urine]] and urinary concentrations vary depending upon [[urine flow rate]] and [[urine pH]].<ref name="inchem" />

The amount of nicotine absorbed by the body from smoking can depend on many factors, including the types of tobacco, whether the smoke is inhaled, and whether a filter is used. However, it has been found that the nicotine yield of individual products has only a small effect (4.4%) on the blood concentration of nicotine,<ref name="Russell_1980">{{cite journal | vauthors = Russell MA, Jarvis M, Iyer R, Feyerabend C | title = Relation of nicotine yield of cigarettes to blood nicotine concentrations in smokers | journal = British Medical Journal | volume = 280 | issue = 6219 | pages = 972–976 | date = April 1980 | pmid = 7417765 | pmc = 1601132 | doi = 10.1136/bmj.280.6219.972 }}</ref> suggesting "the assumed health advantage of switching to lower-tar and lower-nicotine cigarettes may be largely offset by the tendency of smokers to compensate by increasing inhalation".

Nicotine has a half-life of 1–2&nbsp;hours. [[Cotinine]] is an active metabolite of nicotine that remains in the blood with a half-life of 18–20&nbsp;hours, making it easier to analyze.<ref>{{cite journal| vauthors = Bhalala O |title=Detection of Cotinine in Blood Plasma by HPLC MS/MS |journal=MIT Undergraduate Research Journal |volume=8 |date=Spring 2003 |pages=45–50 |url=http://www.docstoc.com/docs/89426297/Detection-of-Cotinine-in-Blood-Plasma-by-HPLC-MS-MS |archive-url=https://web.archive.org/web/20131224105112/http://www.docstoc.com/docs/89426297/Detection-of-Cotinine-in-Blood-Plasma-by-HPLC-MS-MS |archive-date=24 December 2013 }}</ref>

Nicotine is [[metabolized]] in the [[liver]] by [[cytochrome P450]] enzymes (mostly [[CYP2A6]], and also by [[CYP2B6]]) and [[FMO3]], which selectively metabolizes (''S'')-nicotine. A major metabolite is [[cotinine]]. Other primary metabolites include nicotine ''N''-oxide, [[nornicotine]], nicotine isomethonium ion, 2-hydroxynicotine and nicotine glucuronide.<ref name="pmid15734728">{{cite journal | vauthors = Hukkanen J, Jacob P, Benowitz NL | title = Metabolism and disposition kinetics of nicotine | journal = Pharmacological Reviews | volume = 57 | issue = 1 | pages = 79–115 | date = March 2005 | pmid = 15734728 | doi = 10.1124/pr.57.1.3 | s2cid = 14374018 }}</ref> Under some conditions, other substances may be formed such as [[myosmine]].<ref name="Petrick_2011">{{cite journal | vauthors = Petrick LM, Svidovsky A, Dubowski Y | title = Thirdhand smoke: heterogeneous oxidation of nicotine and secondary aerosol formation in the indoor environment | journal = Environmental Science & Technology | volume = 45 | issue = 1 | pages = 328–33 | date = January 2011 | pmid = 21141815 | doi = 10.1021/es102060v | bibcode = 2011EnST...45..328P | s2cid = 206939025 }}</ref><ref>{{cite news |title=''The danger of third-hand smoke: Plain language summary'' – Petrick et al., "Thirdhand smoke: heterogeneous oxidation of nicotine and secondary aerosol formation in the indoor environment" in ''Environmental Science & Technology'' |url=http://www.chromatographyonline.com/danger-third-hand-smoke |work=The Column |issue=3 |publisher=Chromatography Online |date=22 February 2011 |volume=7 |language=en}}</ref>

[[Glucuronidation]] and oxidative metabolism of nicotine to cotinine are both inhibited by [[menthol]], an additive to [[menthol cigarettes|mentholated cigarettes]], thus increasing the half-life of nicotine ''[[in vivo]]''.<ref>{{cite journal | vauthors = Benowitz NL, Herrera B, Jacob P | title = Mentholated cigarette smoking inhibits nicotine metabolism | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 310 | issue = 3 | pages = 1208–15 | date = September 2004 | pmid = 15084646 | doi = 10.1124/jpet.104.066902 | s2cid = 16044557 }}</ref>