Editing Sertraline (section)

====Metabolism====
Sertraline is subject to extensive [[first-pass metabolism]], as indicated by a small study of [[radiolabel]]ed sertraline in which less than 5% of plasma [[radioactivity]] was unchanged sertraline in two males.<ref name="FDALabel" /> The principal [[metabolic pathway]] for sertraline is [[demethylation|''N''-demethylation]] into [[desmethylsertraline]] (''N''-desmethylsertraline) mainly by [[CYP2B6]].<ref name="FDALabel" /><ref name="pmid15547048" /> [[Redox|Reduction]], [[hydroxylation]], and [[glucuronidation|glucuronide]] [[conjugation (biochemistry)|conjugation]] of both sertraline and desmethylsertraline also occur.<ref name="FDALabel" /> Desmethylsertraline, while [[pharmacologically active]], is substantially (50-fold) weaker than sertraline as a [[serotonin reuptake inhibitor]] and its influence on the clinical effects of sertraline is thought to be negligible.<ref name="FDALabel" /><ref name="pmid9400006" /><ref name="In Vivo SERT binding">{{cite journal | vauthors = Sprouse J, Clarke T, Reynolds L, Heym J, Rollema H | title = Comparison of the effects of sertraline and its metabolite desmethylsertraline on blockade of central 5-HT reuptake in vivo | journal = Neuropsychopharmacology | volume = 14 | issue = 4 | pages = 225–231 | date = April 1996 | pmid = 8924190 | doi = 10.1016/0893-133X(95)00112-Q | ref = 1 | s2cid = 39841365 | doi-access = free }}</ref> Based on ''[[in vitro]]'' studies, sertraline is [[metabolism|metabolized]] by multiple [[cytochrome 450]] [[isoenzyme|isoform]]s;<ref name="pmid15547048" >{{cite journal | vauthors = Obach RS, Cox LM, Tremaine LM | title = Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study | journal = Drug Metabolism and Disposition | volume = 33 | issue = 2 | pages = 262–70 | date = February 2005 | pmid = 15547048 | doi = 10.1124/dmd.104.002428 | s2cid = 7254643 }}</ref><ref name="pmid10383917">{{cite journal | vauthors = Kobayashi K, Ishizuka T, Shimada N, Yoshimura Y, Kamijima K, Chiba K | title = Sertraline N-demethylation is catalyzed by multiple isoforms of human cytochrome P-450 in vitro | journal = Drug Metabolism and Disposition | volume = 27 | issue = 7 | pages = 763–6 | date = July 1999 | doi = 10.1016/S0090-9556(24)15222-1 | pmid = 10383917 }}</ref> however, it appears that in the human body [[CYP2C19]] plays the most important role, followed by [[CYP2B6]].<ref name="pmid29136336">{{cite journal |vauthors=Saiz-Rodríguez M, Belmonte C, Román M, Ochoa D, Koller D, Talegón M, Ovejero-Benito MC, López-Rodríguez R, Cabaleiro T, Abad-Santos F |title=Effect of Polymorphisms on the Pharmacokinetics, Pharmacodynamics and Safety of Sertraline in Healthy Volunteers |journal=Basic & Clinical Pharmacology & Toxicology |volume=122 |issue=5 |pages=501–511 |date=May 2018 |pmid=29136336 |doi=10.1111/bcpt.12938 |doi-access=free |hdl=10261/177557 |hdl-access=free }}</ref> In addition to the cytochrome P450 system, sertraline can be [[oxidation|oxidatively]] [[deamination|deaminated]] ''[[in vitro]]'' by [[monoamine oxidase]]s;<ref name="FDALabel" /> however, this [[metabolic pathway]] has never been studied ''[[in vivo]]''.<ref name="pmid15547048" />