Omeprazole Explained

Watchedfields:changed
Verifiedrevid:462265
Chirality:Racemic mixture
Width:200
Width2:200
Tradename:Losec, Prilosec, others
Dailymedid:Omeprazole
Pregnancy Au:B3
Pregnancy Au Comment:[1]
Routes Of Administration:By mouth, intravenous
Class:Proton-pump inhibitor
Atc Prefix:A02
Atc Suffix:BC01
Legal Au:S4
Legal Ca:Rx-only
Legal Ca Comment:[2]
Legal Uk:GSL
Legal Us:OTC
Legal Us Comment:/ Rx-only
Bioavailability:35–76%[3] [4]
Protein Bound:95%
Metabolism:Liver (CYP2C19, CYP3A4)
Elimination Half-Life:1–1.2 hours
Excretion:80% (urine)
20% (bile via feces)
Cas Number:73590-58-6
Pubchem:4594
Iuphar Ligand:4279
Drugbank:DB00338
Chemspiderid:4433
Unii:KG60484QX9
Kegg:D00455
Chebi:7772
Chembl:1503
Pdb Ligand:1C6
Iupac Name:5-Methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1H-benzimidazole
C:17
H:19
N:3
O:3
S:1
Smiles:CC1=CN=C(C(=C1OC)C)CS(=O)C2=NC3=C(N2)C=C(C=C3)OC
Stdinchi:1S/C17H19N3O3S/c1-10-8-18-15(11(2)16(10)23-4)9-24(21)17-19-13-6-5-12(22-3)7-14(13)20-17/h5-8H,9H2,1-4H3,(H,19,20)
Stdinchikey:SUBDBMMJDZJVOS-UHFFFAOYSA-N
Density:1.4±0.1[5]
Melting Point:156

Omeprazole, sold under the brand names Prilosec and Losec, among others, is a medication used in the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease, and Zollinger–Ellison syndrome.[6] It is also used to prevent upper gastrointestinal bleeding in people who are at high risk.[6] Omeprazole is a proton-pump inhibitor (PPI) and its effectiveness is similar to that of other PPIs.[7] It can be taken by mouth or by injection into a vein.[6] [8] It is also available in the fixed-dose combination medication omeprazole/sodium bicarbonate as Zegerid[9] [10] and as Konvomep.[11]

Common side effects include nausea, vomiting, headaches, abdominal pain, and increased intestinal gas.[6] Serious side effects may include Clostridium difficile colitis, an increased risk of pneumonia, an increased risk of bone fractures, and the potential of masking stomach cancer.[6] Whether it is safe for use in pregnancy is unclear.[6] It works by blocking the release of stomach acid.[6]

Omeprazole was patented in 1978, and approved for medical use in 1988.[12] [13] It is on the World Health Organization's List of Essential Medicines.[14] It is available as a generic medication.[6] In 2021, it was the eighth-most commonly prescribed medication in the United States, with more than 54million prescriptions.[15] [16] It is also available without a prescription in the United States.[17] [18]

Medical uses

See also: Proton-pump inhibitor. Omeprazole can be used in the treatment of gastroesophageal reflux disease (GERD), peptic ulcers, erosive esophagitis, Zollinger–Ellison syndrome, and eosinophilic esophagitis.[19] [6]

Peptic ulcers

Peptic ulcers may be treated with omeprazole. Infection with Helicobacter pylori can be treated by taking omeprazole, amoxicillin, and clarithromycin together for 7–14 days.[20] Amoxicillin may be replaced with metronidazole in patients who are allergic to penicillin.[21]

Adverse effects

Adverse effects occurring in at least 1% of people include:[22]

Other concerns related to adverse effects are:

Concern has been expressed regarding vitamin B12[27] and iron malabsorption,[28] but effects seem to be insignificant, especially when supplement therapy is provided.[29]

Since their introduction, proton-pump inhibitors (PPIs, especially omeprazole) have also been associated with several cases of acute interstitial nephritis,[30] an inflammation of the kidneys that often occurs as an adverse drug reaction.

Long-term use

Long-term use of PPIs is strongly associated with the development of benign polyps from fundic glands (which is distinct from fundic gland polyposis); these polyps do not cause cancer and resolve when PPIs are discontinued. No association is seen between PPI use and cancer, but use of PPIs may mask gastric cancers or other serious gastric problems and physicians should be aware of this effect.[31]

There is a possible association between long term use and dementia which requires further study to confirm.[32]

A review article in U.S. Pharmacist in 2013 states that long-term use of PPIs is associated with decreased calcium absorption (causing increased risk of osteoporosis and fractures), decreased magnesium absorption (causing electrolyte disturbances), and increased risk of certain infections such as C. difficile and community-acquired pneumonia. They hypothesize that this is due to decreased stomach acid production.[33]

Pregnancy and breastfeeding

The safety of using omeprazole has not been established in pregnant or breastfeeding women.[34] Epidemiological data do not show an increased risk of major birth defects after maternal use of omeprazole during pregnancy.[35]

Interactions

Important drug interactions are rare.[36] [37] However, the most significant major drug interaction concern is the decreased activation of clopidogrel when taken together with omeprazole.[38] Although still controversial,[39] this may increase the risk of stroke or heart attack in people taking clopidogrel to prevent these events.

This interaction is possible because omeprazole is an inhibitor of the enzymes CYP2C19 and CYP3A4.[40] Clopidogrel is an inactive prodrug that partially depends on CYP2C19 for conversion to its active form. Inhibition of CYP2C19 may block the activation of clopidogrel, which could reduce its effects.[41] [42]

Almost all benzodiazepines are metabolised by the CYP3A4 and CYP2D6 pathways, and inhibition of these enzymes results in a higher area under the curve (i.e., the total effect over time of a given dose). Other examples of drugs dependent on CYP3A4 for their metabolism are escitalopram, warfarin,[43] oxycodone, tramadol, and oxymorphone. The concentrations of these drugs may increase if they are used concomitantly with omeprazole.[44]

Omeprazole is also a competitive inhibitor of p-glycoprotein, as are other PPIs.[45]

Drugs that depend on an acidic stomach environment (such as ketoconazole or atazanavir) may be poorly absorbed, whereas acid-labile antibiotics (such as erythromycin which is a very strong CYP3A4 inhibitor) may be absorbed to a greater extent than normal due to the more alkaline environment of the stomach.[44]

St. John's wort (Hypericum perforatum) and Ginkgo biloba significantly reduce plasma concentrations of omeprazole through induction of CYP3A4 and CYP2C19.[46]

Proton-pump inhibitors like omeprazole have been found to increase the plasma concentrations of methotrexate.[47]

Pharmacology

Omeprazole irreversibly blocks the enzyme system on parietal cells that is needed for the secretion of gastric acid. It is a specific H/KATPase inhibitor. This is the enzyme needed for the final step in the secretion of gastric acid.[48]

Mechanism of action

Omeprazole is a selective and irreversible proton pump inhibitor. It suppresses stomach acid secretion by specific inhibition of the H+/K+-ATPase system found at the secretory surface of gastric parietal cells. Because this enzyme system is regarded as the acid (proton, or H+) pump within the gastric mucosa, omeprazole inhibits the final step of acid production.

Omeprazole also inhibits both basal and stimulated acid secretion irrespective of the stimulus as it blocks the last step in acid secretion. The drug binds non-competitively so it has a dose-dependent effect.[49]

The inhibitory effect of omeprazole occurs within 1 hour after oral administration. The maximum effect occurs within 2 hours. The duration of inhibition is up to 72 hours. When omeprazole is stopped, baseline stomach acid secretory activity returns after 3 to 5 days. The inhibitory effect of omeprazole on acid secretion will plateau after 4 days of repeated daily dosing.[50]

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%.[51] Omeprazole has a volume of distribution of 0.4 L/kg. It has high plasma protein binding of 95%.[49]

Omeprazole, as well as other PPIs, are only effective on active H+/K+-ATPase pumps. These pumps are stimulated in the presence of food to aid in digestion. For this reason, patients should be advised to take omeprazole with a glass of water, before a meal.[52] Additionally, most sources recommend that after taking omeprazole, at least 30 minutes should be allowed to elapse before eating[53] [54] (at least 60 minutes for immediate-release omeprazole plus sodium bicarbonate products, such as Zegerid).

Omeprazole is completely metabolized by the cytochrome P450 system, mainly in the liver, by CYP2C19 and CYP3A4 isoenzymes. Identified metabolites are the sulfone, the sulfide, and hydroxy-omeprazole, which exert no significant effect on acid secretion. 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. Omeprazole has a half life of 0.5 to 1 hour.[55]

Chemistry

Omeprazole contains a tricoordinated sulfinyl sulfur in a pyramidal structure and therefore can exist as either the (S)- or (R)-enantiomers. Omeprazole is a racemate, an equal mixture of the two. In the acidic conditions of the canaliculi of parietal cells, both enantiomers are converted to achiral products (sulfenic acid and sulfenamide configurations) which react with a cysteine group in H+/K+ ATPase, thereby inhibiting the ability of the parietal cells to produce gastric acid.

AstraZeneca also developed esomeprazole (Nexium) which is a eutomer, purely the (S)-enantiomer, rather than a racemate like omeprazole.

Omeprazole undergoes a chiral shift in vivo which converts the inactive (R)-enantiomer to the active (S)-enantiomer, doubling the concentration of the active form.[56] This chiral shift is accomplished by the CYP2C19 isozyme of cytochrome P450, which is not found equally in all human populations. Those who do not metabolize the drug effectively are called "poor metabolizers". 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 tailored according to CYP2C19 metabolism status.[57]

Measurement in body fluids

Omeprazole may be quantified in plasma or serum to monitor therapy or to confirm a diagnosis of poisoning in hospitalized patients. Plasma omeprazole concentrations are usually in a range of 0.2–1.2 mg/L in persons receiving the drug therapeutically by the oral route and 1–6 mg/L in people with acute overdose. Enantiomeric chromatographic methods are available to distinguish esomeprazole from racemic omeprazole.[58]

History

See main article: Discovery and development of proton pump inhibitors. Omeprazole was first made in 1979 by Swedish AB Hässle, part of Astra AB. It was the first of the proton pump inhibitors (PPI).[59] [60] Astra AB, now AstraZeneca, launched it as an ulcer medicine under the name Losec in Sweden. It was first sold in the United States in 1989 under the brand name Losec. In 1990, at the request of the U.S. Food and Drug Administration, the brand name Losec was changed to Prilosec to avoid confusion with the diuretic Lasix (furosemide).[61] The new name led to confusion between omeprazole (Prilosec) and fluoxetine (Prozac), an antidepressant.

Society and culture

Economics

When Prilosec's U.S. patent expired in April 2001, AstraZeneca introduced esomeprazole (Nexium) as a patented replacement drug.[62] Many companies introduced generics as AstraZeneca's patents expired worldwide, which are available under many brand names.

Omeprazole was a subject of a patent litigation in the U.S.[63] The invention involvedapplication of two different coatings to a drug in pill form to ensure, that the omeprazole did not disintegrate before reaching its intended site of action in stomach. Although the solution by means of two coating was obvious, the patent was found valid, because the source of the problem was non-obvious and was discovered by the patentee.[64]

In September 2023, AstraZeneca announced it would pay $425 million to settle product liability litigations against Prilosec in the United States.[65]

Brand names

Brand names include Losec, Prilosec, Zegerid, Miracid, and Omez.[66] [6]

Further reading

Notes and References

  1. Web site: Omeprazole Use During Pregnancy . Drugs.com . 11 April 2019 . 15 February 2020 . 15 February 2020 . https://web.archive.org/web/20200215230433/https://www.drugs.com/pregnancy/omeprazole.html . live .
  2. Web site: Product monograph brand safety updates . . 7 July 2016 . 1 April 2024.
  3. Web site: Prilosec- omeprazole magnesium capsule, delayed release Prilosec- omeprazole magnesium granule, delayed release . DailyMed . 22 December 2016 . 15 February 2020 . 27 December 2019 . https://web.archive.org/web/20191227184048/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a1b077e6-b070-43f2-a98e-380cc635419d . live .
  4. Vaz-da-Silva M, Loureiro AI, Nunes T, Maia J, Tavares S, Falcão A, Silveira P, Almeida L, Soares-da-Silva P . Bioavailability and bioequivalence of two enteric-coated formulations of omeprazole in fasting and fed conditions . Clinical Drug Investigation . 25 . 6 . 391–399 . 2005 . 17532679 . 10.2165/00044011-200525060-00004 . live . 21 October 2018 . 22082780 . https://web.archive.org/web/20130313204630/http://www.medscape.com/viewarticle/508018 . 13 March 2013 .
  5. Web site: Omeprazole MSDS . 21 October 2018 . 19 April 2017 . https://web.archive.org/web/20170419120322/http://www.chemsrc.com/en/cas/73590-58-6_591579.html . live .
  6. Web site: Omeprazole . The American Society of Health-System Pharmacists . 21 October 2018 . 19 February 2011 . https://web.archive.org/web/20110219135631/http://www.drugs.com/monograph/omeprazole.html . live .
  7. Web site: [99] Comparative effectiveness of proton pump inhibitors Therapeutics Initiative]. 14 July 2016. 28 June 2016. 30 October 2020. https://web.archive.org/web/20201030063031/https://www.ti.ubc.ca/2016/06/28/99-comparative-effectiveness-proton-pump-inhibitors/. live.
  8. Web site: Omeprazole 40 mg Powder for Solution for Infusion . EMC . 21 October 2018 . 10 February 2016 . live . https://web.archive.org/web/20160407193540/https://www.medicines.org.uk/emc/medicine/25259 . 7 April 2016.
  9. Web site: Zegerid- omeprazole and sodium bicarbonate powder, for suspension Zegerid- omeprazole and sodium bicarbonate capsule . DailyMed . 4 March 2022 . 16 December 2022.
  10. Web site: Zegerid OTC- omeprazole and sodium bicarbonate capsule, gelatin coated . DailyMed . 5 December 2022 . 16 December 2022.
  11. Web site: Konvomep- omeprazole and sodium bicarbonate kit . DailyMed . 30 August 2022 . 21 January 2023.
  12. Web site: Drug Approval Package: Prilosec (Omeprazole) NDA# 019-810s38s50s5 . U.S. Food and Drug Administration (FDA) . 30 March 2001 . 5 October 2022 . 1 April 2021 . https://web.archive.org/web/20210401151454/https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/019810s38s50s56.cfm . live .
  13. Book: Fischer J, Ganellin CR . Analogue-based Drug Discovery . 2006 . John Wiley & Sons . 9783527607495 . 445 . 29 June 2020 . 3 August 2020 . https://web.archive.org/web/20200803230101/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA445 . live .
  14. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 21st list 2019 . 2019 . 10665/325771 . World Health Organization . World Health Organization . Geneva . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO . free .
  15. Web site: The Top 300 of 2021 . ClinCalc . 14 January 2024 . 15 January 2024 . https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx . live .
  16. Web site: Omeprazole - Drug Usage Statistics, ClinCalc DrugStats Database . ClinCalc . 14 January 2024 .
  17. Web site: Questions and Answers on Prilosec OTC (omeprazole) . U.S. Food and Drug Administration (FDA) . 2 March 2020 . 3 November 2018 . 28 August 2021 . https://web.archive.org/web/20210828195503/https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/questions-and-answers-prilosec-otc-omeprazole . live .
  18. Web site: Drug Approval Package: Prilosec (Omeprazole Magnesium) NDA #021229 . U.S. Food and Drug Administration (FDA) . 6 October 2022 . 24 January 2022 . https://web.archive.org/web/20220124210732/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-229_Prilosec.cfm . live .
  19. Cheng E . Proton pump inhibitors for eosinophilic oesophagitis . Current Opinion in Gastroenterology . 29 . 4 . 416–420 . July 2013 . 23449027 . 4118554 . 10.1097/MOG.0b013e32835fb50e .
  20. Fuccio L, Minardi ME, Zagari RM, Grilli D, Magrini N, Bazzoli F . Meta-analysis: duration of first-line proton-pump inhibitor based triple therapy for Helicobacter pylori eradication . Annals of Internal Medicine . 147 . 8 . 553–562 . October 2007 . 17938394 . 10.7326/0003-4819-147-8-200710160-00008 . 11644009 .
  21. Malfertheiner P, Megraud F, O'Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers EJ . Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report . Gut . 56 . 6 . 772–781 . June 2007 . 17170018 . 1954853 . 10.1136/gut.2006.101634 .
  22. McTavish D, Buckley MM, Heel RC . Omeprazole. An updated review of its pharmacology and therapeutic use in acid-related disorders . Drugs . 42 . 1 . 138–170 . July 1991 . 1718683 . 10.2165/00003495-199142010-00008 .
  23. Abou Chakra CN, Pepin J, Sirard S, Valiquette L . Risk factors for recurrence, complications and mortality in Clostridium difficile infection: a systematic review . PLOS ONE . 9 . 6 . e98400 . 21 June 2014 . 24897375 . 4045753 . 10.1371/journal.pone.0098400 . 2014PLoSO...998400A . free .
  24. Yang YX, Lewis JD, Epstein S, Metz DC . Long-term proton pump inhibitor therapy and risk of hip fracture . JAMA . 296 . 24 . 2947–2953 . December 2006 . 17190895 . 10.1001/jama.296.24.2947 . free .
  25. Yu EW, Bauer SR, Bain PA, Bauer DC . Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies . The American Journal of Medicine . 124 . 6 . 519–526 . June 2011 . 21605729 . 3101476 . 10.1016/j.amjmed.2011.01.007 .
  26. Hess MW, Hoenderop JG, Bindels RJ, Drenth JP . Systematic review: hypomagnesaemia induced by proton pump inhibition . Alimentary Pharmacology & Therapeutics . 36 . 5 . 405–413 . September 2012 . 22762246 . 10.1111/j.1365-2036.2012.05201.x . 9073390 . free .
  27. Neal K, Logan R . Potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors . Alimentary Pharmacology & Therapeutics . 15 . 7 . 1085–1086 . July 2001 . 11421886 . 10.1046/j.1365-2036.2001.0994a.x . 39455836 . free .
  28. Sarzynski E, Puttarajappa C, Xie Y, Grover M, Laird-Fick H . Association between proton pump inhibitor use and anemia: a retrospective cohort study . Digestive Diseases and Sciences . 56 . 8 . 2349–2353 . August 2011 . 21318590 . 10.1007/s10620-011-1589-y . 33574008 .
  29. McColl KE . Effect of proton pump inhibitors on vitamins and iron . The American Journal of Gastroenterology . 104 . Suppl 2 . S5–S9 . March 2009 . 19262546 . 10.1038/ajg.2009.45 . 31455416 .
  30. Härmark L, van der Wiel HE, de Groot MC, van Grootheest AC . Proton pump inhibitor-induced acute interstitial nephritis . British Journal of Clinical Pharmacology . 64 . 6 . 819–823 . December 2007 . 17635502 . 2198775 . 10.1111/j.1365-2125.2007.02927.x .
  31. Corleto VD, Festa S, Di Giulio E, Annibale B . Proton pump inhibitor therapy and potential long-term harm . Current Opinion in Endocrinology, Diabetes, and Obesity . 21 . 1 . 3–8 . February 2014 . 24310148 . 10.1097/med.0000000000000031 . 205791135 . 11573/618643 .
  32. Eusebi LH, Rabitti S, Artesiani ML, Gelli D, Montagnani M, Zagari RM, Bazzoli F . Proton pump inhibitors: Risks of long-term use . Journal of Gastroenterology and Hepatology . 32 . 7 . 1295–1302 . July 2017 . 28092694 . 10.1111/jgh.13737 . free .
  33. O'Neill LW, Culpepper BL, Galdo JA . Long-Term Consequences of Chronic Proton Pump Inhibitor Use . US Pharmacist . 2013 . 38 . 12 . 38–42 . 28 December 2020 . 21 January 2021. https://web.archive.org/web/20210121163435/https://www.uspharmacist.com/article/longterm-consequences-of-chronic-proton-pump-inhibitor-use. live.
  34. Book: Davis's Drug Guide for Nurses. Vallerand AH, Sanoski CA, Deglin JH . F.A. Davis Company. 2015. 978-0-8036-4085-6. 14th. 924–925. 881473728.
  35. Pasternak B, Hviid A . Use of proton-pump inhibitors in early pregnancy and the risk of birth defects . The New England Journal of Medicine . 363 . 22 . 2114–2123 . November 2010 . 21105793 . 10.1056/NEJMoa1002689 . 10954538 . free .
  36. Web site: Fitzakerley J . 2014 Treatments for Acid-Peptic Diseases. . 21 October 2018. dead . https://web.archive.org/web/20140419014436/http://www.d.umn.edu/~jfitzake/Lectures/DMED/Antiulcer/Treatment/ReducePain/PPIs/PPIsSE.html . 19 April 2014 . University of Minnesota Medical School Duluth.
  37. Web site: Proton Pump Inhibitor: Use in Adults . https://web.archive.org/web/20131212143828/http://www.cms.gov/Medicare-Medicaid-Coordination/Fraud-Prevention/Medicaid-Integrity-Education/Pharmacy-Education-Materials/Downloads/ppi-adult-factsheet.pdf . 12 December 2013 . 21 October 2018 . CMS Medicaid Integrity Program.
  38. Douglas IJ, Evans SJ, Hingorani AD, Grosso AM, Timmis A, Hemingway H, Smeeth L . Clopidogrel and interaction with proton pump inhibitors: comparison between cohort and within person study designs . BMJ . 345 . e4388 . July 2012 . 22782731 . 3392956 . 10.1136/bmj.e4388 .
  39. Focks JJ, Brouwer MA, van Oijen MG, Lanas A, Bhatt DL, Verheugt FW . Concomitant use of clopidogrel and proton pump inhibitors: impact on platelet function and clinical outcome- a systematic review . Heart . 99 . 8 . 520–527 . April 2013 . 22851683 . 10.1136/heartjnl-2012-302371 . 23689175 .
  40. Shirasaka Y, Sager JE, Lutz JD, Davis C, Isoherranen N . Inhibition of CYP2C19 and CYP3A4 by omeprazole metabolites and their contribution to drug-drug interactions . Drug Metabolism and Disposition . 41 . 7 . 1414–1424 . July 2013 . 23620487 . 3684819 . 10.1124/dmd.113.051722 .
  41. Lau WC, Gurbel PA . The drug-drug interaction between proton pump inhibitors and clopidogrel . CMAJ . 180 . 7 . 699–700 . March 2009 . 19332744 . 2659824 . 10.1503/cmaj.090251 .
  42. Norgard NB, Mathews KD, Wall GC . Drug-drug interaction between clopidogrel and the proton pump inhibitors . The Annals of Pharmacotherapy . 43 . 7 . 1266–1274 . July 2009 . 19470853 . 10.1345/aph.1M051 . 13227312 .
  43. Daly AK, King BP . Pharmacogenetics of oral anticoagulants . Pharmacogenetics . 13 . 5 . 247–252 . May 2003 . 12724615 . 10.1097/00008571-200305000-00002 .
  44. Stedman CA, Barclay ML . Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors . Alimentary Pharmacology & Therapeutics . 14 . 8 . 963–978 . August 2000 . 10930890 . 10.1046/j.1365-2036.2000.00788.x . 45337685 .
  45. Pauli-Magnus C, Rekersbrink S, Klotz U, Fromm MF . Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein . Naunyn-Schmiedeberg's Archives of Pharmacology . 364 . 6 . 551–557 . December 2001 . 11770010 . 10.1007/s00210-001-0489-7 . 19990184 .
  46. Izzo AA, Ernst E . Interactions between herbal medicines and prescribed drugs: an updated systematic review . Drugs . 69 . 13 . 1777–1798 . 2009 . 19719333 . 10.2165/11317010-000000000-00000 . 25720882 .
  47. Web site: Methotrexate . Martindale: The Complete Drug Reference . Pharmaceutical Press . 6 January 2014 . 12 April 2014 . Brayfield A . 28 August 2021 . https://web.archive.org/web/20210828170949/https://about.medicinescomplete.com/wp-content/plugins/revslider/public/assets/js/jquery.themepunch.revolution.min.js?ver=5.4.5.2 . live .
  48. Howden CW . Clinical pharmacology of omeprazole . Clinical Pharmacokinetics . 20 . 1 . 38–49 . January 1991 . 2029801 . 10.2165/00003088-199120010-00003 . 25855436 .
  49. Clissold SP, Campoli-Richards DM . Omeprazole. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peptic ulcer disease and Zollinger-Ellison syndrome . Drugs . 32 . 1 . 15–47 . July 1986 . 3527658 . 10.2165/00003495-198632010-00002 .
  50. Web site: Omeprazole package insert . https://web.archive.org/web/20140419020303/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=bced816b-6927-49fb-851f-f83a678dac97 . 19 April 2014 . India . Dr. Reddy's Laboratories Limited . June 2013 .
  51. Cederberg C, Andersson T, Skånberg I . Omeprazole: pharmacokinetics and metabolism in man . Scandinavian Journal of Gastroenterology. Supplement . 166 . sup166 . 33–40 . 1 January 1989 . 2690330 . 10.3109/00365528909091241 .
  52. Katz PO, Gerson LB, Vela MF . Guidelines for the diagnosis and management of gastroesophageal reflux disease . The American Journal of Gastroenterology . 108 . 3 . 308–28; quiz 329 . March 2013 . 23419381 . 10.1038/ajg.2012.444 . 8198975 . free .
  53. Web site: Omeprazole, in The Free Medical Dictionary. 11 November 2010. 12 June 2011. https://web.archive.org/web/20110612172513/http://medical-dictionary.thefreedictionary.com/omeprazole. live.
  54. Web site: Omeprazole. Drugs.com. 11 November 2010. live. https://web.archive.org/web/20110219135631/http://www.drugs.com/monograph/omeprazole.html. 19 February 2011.
  55. Web site: Omeprazole . www.drugbank.ca . 29 January 2019 . 30 January 2019 . https://web.archive.org/web/20190130053122/https://www.drugbank.ca/drugs/DB00338 . live .
  56. Web site: Nexium Prescribing Information . https://web.archive.org/web/20091008000830/http://www1.astrazeneca-us.com/pi/Nexium.pdf . 8 October 2009 . AstraZeneca Pharmaceuticals .
  57. Furuta T, Shirai N, Sugimoto M, Nakamura A, Hishida A, Ishizaki T . Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies . Drug Metabolism and Pharmacokinetics . 20 . 3 . 153–167 . June 2005 . 15988117 . 10.2133/dmpk.20.153 . 19090952 .
  58. Baselt RC, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1146–7. .
  59. Web site: Trends in Drug Patenting - Case Studies: THE CASES: 5. OMEPRAZOLE. https://web.archive.org/web/20101002080328/http://apps.who.int/medicinedocs/en/d/Js4915e/2.5.html. dead. 2 October 2010. apps.who.int. 22 August 2019.
  60. Fellenius E, Berglindh T, Sachs G, Olbe L, Elander B, Sjöstrand SE, Wallmark B . Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+)ATPase . Nature . 290 . 5802 . 159–161 . March 1981 . 6259537 . 10.1038/290159a0 . 4368190 . 1981Natur.290..159F .
  61. Farley D . Making it easier to read prescriptions . FDA Consumer . 29 . 6 . 25–27 . July–August 1995 . 10143448 . dead . 26 January 2011 . https://web.archive.org/web/20120315172345/http://www.thebody.com/content/art13913.html . 15 March 2012 .
  62. News: Prilosec's Maker Switches Users To Nexium, Thwarting Generics . Harris G . The Wall Street Journal . 6 June 2002 . live . https://web.archive.org/web/20170806181248/https://www.wsj.com/articles/SB1023326369679910840 . 6 August 2017.
  63. AstraZeneca awarded damages in Prilosec patent litigation . AstraZeneca . 3 December 2013 . 4 October 2023.
  64. Web site: IN RE OMEPRAZOLE PATENT LITIGATION, Court of Appeals, Federal Circuit 2011 - Google Scholar .
  65. News: 3 October 2023 . AstraZeneca to pay $425 mln to settle Nexium, Prilosec litigation in US . Reuters . 3 October 2023.
  66. Web site: Omeprazole international . Drugs.com . 3 February 2020 . 27 February 2020 . 28 February 2020 . https://web.archive.org/web/20200228060551/https://www.drugs.com/international/omeprazole.html . live .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Omeprazole".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.