Esomeprazole 769166 223834363 2008-07-06T01:39:30Z Andros 1337 83945 {{redirect|Purple pill|[[D12]] song|Purple Pills}} {{redirect|Purple pill|[[D12]] song|Purple Pills}} {{Drugbox| |IUPAC_name = (''S'')-5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)<br />methylsulfinyl]-3''H''-benzoimidazole | width=250 | image=Esomeprazole.png | CAS_number=161796-78-7 | ATC_prefix=A02 | ATC_suffix=BC05 | ATC_supplemental= | PubChem=4594 | DrugBank=APRD00363 | C=17 | H=19 | N=3 | O=3 | S=1 | molecular_weight = 345.417 g/mol | smiles = COc1ccc2nc([nH]c2c1)S(=O)Cc1ncc(C)c(OC)c1C | bioavailability= 50 to 90% | metabolism = [[Liver|Hepatic]] ([[CYP2C19]], [[CYP3A4]]) | elimination_half-life= 1–1.5 hours | excretion = 80% [[Kidney|Renal]]<br>20% [[feces|faecal]] | pregnancy_AU = B3 | legal_AU = S4 | legal_UK = POM | legal_US = Rx-only | routes_of_administration= Oral, [[Intravenous therapy|IV]] }} '''Esomeprazole''' ({{pronEng|ɛsoʊˈmɛprəzoʊl}}) is a [[proton pump inhibitor]] (brand names '''Sompraz''', '''Zoleri''', '''Nexium''', '''Lucen''', '''Esopral'''; '''Axagon''' in Italy) developed and marketed by [[AstraZeneca]] which is used in the treatment of [[dyspepsia]], [[peptic ulcer|peptic ulcer disease]] (PUD), [[gastroesophageal reflux disease]] (GORD/GERD) and [[Zollinger-Ellison syndrome]]. Esomeprazole is the ''S''-[[enantiomer]] of [[omeprazole]] (marketed as Losec/Prilosec), and AstraZeneca claims improved [[efficacy]] of this single enantiomer product over the [[racemic]] mixture of omeprazole. However, this greater efficacy has been disputed, with some claiming it offers no benefit from its older form. (see below). Esomeprazole was the third biggest selling pharmaceutical drug in the world for 2005, totaling [[United States dollar|US$]] 5.7 billion in sales.{{Fact|date=June 2007}} ==Pharmacology== {{main|Proton pump inhibitor}} Esomeprazole is a proton pump inhibitor which reduces [[Stomach|gastric]] acid secretion through inhibition of H<sup>+</sup>/K<sup>+</sup>-ATPase in gastric [[parietal cell]]s. By inhibiting the functioning of this enzyme, the drug prevents formation of gastric acid. ==Clinical use== {{main|Proton pump inhibitor}} ===Use in ''Helicobacter pylori'' eradication=== Esomeprazole is combined with the antibiotics [[clarithromycin]] and [[amoxicillin]] (or [[metronidazole]]) in the 7-day eradication triple therapy for ''[[Helicobacter pylori]]''. Infection by ''H. pylori'' is the causative factor in the majority of [[Peptic ulcer|peptic and duodenal ulcers]]. ==Evidence of efficacy== AstraZeneca claims that esomeprazole provides improved efficacy, in terms of stomach acid control, over racemic omeprazole. Many health professionals have expressed the view that this improvement in efficacy is due to the dose of esomeprazole recommended for therapy rather than any superiority of esomeprazole ''per se''. An alternative rationale suggested for the use of esomeprazole was the reduction in interindividual variability in efficacy. However the clinical advantage of this hypothesis has not thoroughly been tested in large-scale trials.{{ref label|Somogyi|Somogyi 2004|Somogyi 2004}} Given the large difference in cost between all other proton pump inhibitors and that of Prilosec-OTC (equivalent to omeprazole 20mg), many physicians recommend a trial of over-the-counter products before beginning more extensive therapies and testing. Although the (S)-isomer is more potent in humans, the (R)-isomer is more potent in the testing of rats, while the enantiomers are equipotent in dogs. ( "The Organic Chemistry of Drug Design and Drug Action, Richard B. Silverman, page 148) ==Dosage forms== Esomeprazole is available as delayed-release capsules in the United States or as delayed release tablets in Australia and Canada (containing esomeprazole magnesium) in strengths of 20 mg and 40 mg; and as esomeprazole sodium for [[intravenous]] injection/infusion. Oral esomeprazole preparations are [[enteric coating|enteric-coated]], due to the rapid degradation of the drug in the [[acid]]ic conditions of the [[stomach]]. This is achieved by formulating capsules using the multiple-unit pellet system. [[Image:Nexium (esomeprazole magnesium) pills.JPG|thumb|40 mg Nexium brand esomeprazole capsules]] ===Multiple unit pellet system=== Esomeprazole capsules are formulated as a "multiple unit pellet system" (MUPS). Essentially, the [[capsule]] consists of extremely small enteric-coated granules (pellets) of the esomeprazole formulation inside an outer shell. When the capsule is immersed in an aqueous solution, as happens when the capsule reaches the stomach, water enters the capsule by [[osmosis]]. The contents swell from water absorption causing the shell to burst, releasing the enteric-coated granules. For most patients, the multiple-unit pellet system is of no advantage over conventional enteric-coated preparations. Patients for which the formulation is of benefit include those requiring [[nasogastric tube]] feeding and those with difficulty swallowing ([[dysphagia]]). The granules are manufactured in a [[fluid bed]] system with small sugar spheres as the starting material. The sugar spheres are sequentially spray-coated with a [[Suspension (chemistry)|suspension]] containing esomeprazole, a protective layer to prevent degradation of the drug in manufacturing, an enteric coating and an outer layer to reduce granule aggregation. The granules are mixed with other inactive [[excipient]]s and compressed into tablets. Finally, the tablets are film-coated to improve the stability and appearance of the preparation. ==Financial impact== Between the launch of esomeprazole in 2001 and 2005, the drug has netted AstraZeneca about $14.4 billion.<ref>Financial impact information: [http://www.astrazeneca.com/sites/7/imagebank/typeArticleparam511672/astrazeneca-2005-annual-review.pdf 2005, $4.6 billion]; [http://www.astrazeneca.com/sites/7/imagebank/typearticleparam511562/astrazeneca-2004-annual-report.pdf 2004, $3.9 billion]; [http://www.astrazeneca.com/sites/7/imagebank/typearticleparam503063/AstraZeneca%20Annual%20Report%202003.pdf 2003, $3.3 billion]; [http://www2.astrazeneca.com/annualrep2002/pdf/694617_Report_front.pdf 2002, $2 billion]; [http://www2.astrazeneca.com/annualrep2001/pdf/first.pdf 2001, launch and $580 million].</ref> ==Controversy== There has been some controversy about [[AstraZeneca]]'s behaviour in creating, patenting and marketing of the drug. Critics allege that the drug's successful predecessor [[Omeprazole]] is a mixture of two [[Chirality (chemistry)|mirror-imaged molecules]] (esomeprazole and romeprazole), and that the company was trying to "evergreen" its patent by patenting the pure esomeprazole and aggressively marketing to doctors{{ref|NexiumDisNY}} that it is more effective than the mixture, claiming that romeprazole has no beneficial effects on the patient. However, in the acidic environment of the [[parietal cells]] both esomeprazole and romeprazole are converted to the same active drug which stops the gastric acid production. [[Dr. Marcia Angell]], former Editor in Chief of the New England Journal of Medicine, spoke at [[Harvard Medical School]] to a German magazine on August 16, 2007 and accused AstraZeneca's scientists of deceptively doctoring their comparative studies such that the difference to Omeprazole would look larger, providing a marketing advantage {{ref|Stern}}. For more information, see [[AstraZeneca#Nexium|AstraZeneca's article]]. ==References== * {{note label|Lind|Lind 2004|Lind 2004}} {{cite journal | quotes = | last = Lind | first = T. | coauthors = Rydberg L., Kyleback A., Jonsson A., Andersson T., Hasselgren T., Holmberg J., Rohss K. | year = 2000 | month = July | title = Esomeprazole provides improved acid control vs. omeprazole In patients with symptoms of gastro-oesophageal reflux disease | journal = [[Alimentary pharmacology & therapeutics]] | volume = 14 | issue = 7 | pages = 861&ndash;867 | doi = | pmid = 10886041 | url = | accessdate = 2006-12-02 }} *{{note label|Somogyi|Somogyi 2004|Somogyi 2004}} Somogyi A., Bochner F., Foster D. (2004). Inside the isomers: the tale of chiral switches. ''Aust Prescr'' '''27''', 47-49. * {{cite news | first = Malcolm | last = Gladwell | authorlink = Malcolm Gladwell | title = High Prices: How to think about prescription drugs. | url = http://www.newyorker.com/critics/atlarge/?041025crat_atlarge | work = A Critic At Large | publisher = [[The New Yorker]] | date = 2004-10-25 | accessdate = 2006-12-02 }} ''This article describes AstraZeneca's strategy for developing Nexium as a follow-on for Losec as the latter approached patent expiry.'' ===Notes=== # {{note|NexiumDisNYT}} Gladwell, Malcolm (October 25, 2004). "[http://www.newyorker.com/critics/atlarge/?041025crat_atlarge High Prices: How to think about prescription drugs]". ''[[The New Yorker]]''. Verified availability August 19, 2007. # {{note|Stern}} Grill, Markus and Hansen, Hans: "Vorsicht, Pharma! Wie die Industrie Ärzte manipuliert und Patienten täuscht." ('Caution, Pharma! How the industry manipulates physicians and deceives patients.') Published in the 16.08.2007 issue of the magazine [[Stern (magazine)|"Der Stern"]] (Germany; pp. 100-107). Available as an e-paper [http://www.stern.de/magazin/heft/595225.html here]. }} {{reflist}} ==External links== * [http://www.nexium.net The official International Nexium website] * [http://www.purplepill.com The official U.S. Nexium website] {{Proton-Pump Inhibitors}} [[Category:Proton pump inhibitors]] [[Category:AstraZeneca]] [[Category:Benzimidazoles]] [[Category:Sulfoxides]] [[Category:Pyridines]] [[de:Esomeprazol]] [[it:Esomeprazolo]] [[hu:Ezomeprazol]] [[nl:Esomeprazol]] [[pl:Esomeprazol]] [[ru:Эзомепразол]] [[tr:Esomeprazol]]