Editing Omeprazole (section)

===Pharmacokinetics===
The absorption of omeprazole takes place in the small intestine and is usually completed within 3 to 6 hours. The systemic [[bioavailability]] of omeprazole after repeated doses is about 60%.<ref>{{cite journal | vauthors = Cederberg C, Andersson T, Skånberg I | title = Omeprazole: pharmacokinetics and metabolism in man | journal = Scandinavian Journal of Gastroenterology. Supplement | volume = 166 | issue = sup166 | pages = 33–40 | date = 1 January 1989 | pmid = 2690330 | doi = 10.3109/00365528909091241 }}</ref> Omeprazole has a volume of distribution of 0.4 L/kg. It has high plasma protein binding of 95%.<ref name="Omeprazole"/>

<!-- Metabolism -->
Omeprazole is completely metabolized by the [[cytochrome P450]] system, mainly in the liver, by [[CYP2C19]] and [[CYP3A4]] [[Isozyme|isoenzymes]].<ref name=Dav2015 /> Identified metabolites are the [[sulfone]], the [[sulfide]], and hydroxy-omeprazole. About 77% of an orally given dose is excreted as metabolites in the urine, and the remainder is found in the feces, primarily originating from bile secretion.<ref name=":1" /> Omeprazole has a half life of 0.5 to 1 hour.<ref name=":1">{{cite web |title=Omeprazole |url=https://www.drugbank.ca/drugs/DB00338 |website=www.drugbank.ca |access-date=29 January 2019 |archive-date=30 January 2019 |archive-url=https://web.archive.org/web/20190130053122/https://www.drugbank.ca/drugs/DB00338 |url-status=live }}</ref>

==== Bioactivation ====
As with all structually-similar benzimidazole [[proton pump inhibitor]]s, omeprazole is a [[prodrug]]. A basic molecule, it accumulates in the acidic [[canaliculus (parietal cell)|canaliculi]] of [[parietal cells]] in a protonated form where the S=O group becomes S-OH, which in turn is interconvertible with an achiral, reactive [[sulfonamide]] form. The sulfonamide form is able to attach onto the [[cysteine]] residue on the H<sup>+</sup>/K<sup>+</sup>-ATPase, thereby irreversibly inhibiting it.<ref name=Huttunen>{{cite journal | vauthors = Huttunen KM, Raunio H, Rautio J | title = Prodrugs--from serendipity to rational design | journal = Pharmacological Reviews | volume = 63 | issue = 3 | pages = 750–771 | date = September 2011 | pmid = 21737530 | doi = 10.1124/pr.110.003459 }}</ref>

: [[File:Omeprazole Mechanism V1.svg|class=skin-invert-image|500px|Omeprazol rearrangement in the body]]

This process is not affected by chirality, by AstraZeneca's own admission.<ref name="www1.astrazeneca-us.com">{{cite web | url = http://www1.astrazeneca-us.com/pi/Nexium.pdf | title = Nexium Prescribing Information | archive-url = https://web.archive.org/web/20091008000830/http://www1.astrazeneca-us.com/pi/Nexium.pdf | archive-date=8 October 2009 | publisher = AstraZeneca Pharmaceuticals }}</ref>

==== Chirality ====
The two different chiralities of omeprazole are both metabolized into inactive products by [[cytochrome P450]] enzymes, but each chirality are differently inactivated by specific isozymes. Compared to the (''R'')-enantiomer, the (''S'')-enantiomer is relatively more resistant to metabolism, especially metabolism by [[CYP2C19]]<ref>{{cite journal | vauthors = Roche VF | title = The chemically elegant proton pump inhibitors | journal = American Journal of Pharmaceutical Education | volume = 70 | issue = 5 | pages = 101 | date = October 2006 | pmid = 17149430 | doi = 10.5688/aj7005101 | pmc = 1637016 }}</ref> (if it's processed by CYP2C19 at all).<ref>{{cite journal | vauthors = Shiohira H, Yasui-Furukori N, Yamada S, Tateishi T, Akamine Y, Uno T | title = Hydroxylation of R(+)- and S(-)-omeprazole after racemic dosing are different among the CYP2C19 genotypes | journal = Pharmaceutical Research | volume = 29 | issue = 8 | pages = 2310–2316 | date = August 2012 | pmid = 22549736 | doi = 10.1007/s11095-012-0757-x }}</ref> As a result, among people with a more active version of CYP2C19 ("extensive metabolizers"), the (''R'') half of a dose of omeprazole is likely to perform more poorly. Conversely, among those with a less active version of CYP2C19 ("poor metabolizers"), more the (''R'') half is expected to survive metabolism and end up useful. The proportion of the poor metabolizer [[phenotype]] varies widely between populations, from 2.0 to 2.5% in African Americans and white Americans to >20% in Asians. Several [[pharmacogenomics]] studies have suggested that PPI treatment should be [[personalized medicine|tailored]] according to CYP2C19 metabolism status.<ref>{{cite journal | vauthors = Furuta T, Shirai N, Sugimoto M, Nakamura A, Hishida A, Ishizaki T | title = Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies | journal = Drug Metabolism and Pharmacokinetics | volume = 20 | issue = 3 | pages = 153–167 | date = June 2005 | pmid = 15988117 | doi = 10.2133/dmpk.20.153 | s2cid = 19090952 }}</ref>

[[AstraZeneca]] also [[drug development|developed]] [[esomeprazole]] (Nexium) which is a [[eutomer]], purely the (''S'')-enantiomer, rather than a racemate like omeprazole.<ref name="www1.astrazeneca-us.com"/>