Esomeprazole (Esostom):
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Esomeprazole
Systematic (IUPAC)=20 name
(S)-5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)
met= hylsulfinyl]-3H-benzoimidazole
Identifiers
CAS = number
161796-78-7
ATC=20 code A02BC05
PubChem
4594
DrugBank
APRD00363
Chemical data
Formula C17H19N3O3S
Mol. = mass
345.417 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic = data
Bioavailability= 50 to 90%
Metabolism= Hepatic (CYP2C19, CYP3A4)
Half = life
1=E2=80=931.5 hours
Excretion
80% Renal
20% faecal
Therapeutic = considerations
Pregnancy = cat.
B3(AU)<= /TR>
Leg= al=20 status Prescription = Only (S4)(AU)<= /TR>
Routes<= /TD> Oral, IV
Esomeprazole (pronounced = /=C9=9Bso=CA=8A=CB=88m=C9=9Bpr=C9=99zo=CA=8Al/)=20 is a proton pump=20 inhibitor (brand names Nexium=C2=AE; Lucen=C2=AE; = Esopral=C2=AE and=20 Axagon=C2=AE in Italy) developed and marketed by AstraZeneca which = is used in=20 the treatment of dyspepsia, peptic ulcer = disease (PUD),=20 gas= troesophageal=20 reflux disease (GORD/GERD) and Zollinge= r-Ellison=20 syndrome. Esomeprazole is the S-enantiomer of omeprazole=20 (marketed as Losec/Prilosec), and AstraZeneca claims improved efficacy of this = single=20 enantiomer product over the racemic mixture of = omeprazole.=20 However, this greater efficacy has been disputed, with some claiming it = offers=20 no benefit from its older form. (see below). Esomeprazole was the third = biggest=20 selling pharmaceutical drug in the world for 2005, totaling $5.7 billion = in=20 sales.[citation = needed]
Contents
• 1 Pharmacology=20
• 2 Clinical = use=20
o 2.1 Use in = Helicobacter=20 pylori eradication
• <= SPAN=20 class=3Dtocnumber>3 Evidence of=20 efficacy=20
• 4 Dosage = forms=20
o 4.1 Multiple = unit pellet=20 system
• 5 Financial = impact=20
• 6 Controversy=20
• 7 References=20
o 7.1 Notes=20
• 8 External = links=20
[edit]=20 Pharmacology
Main article: Proton = pump=20 inhibitor
Esomeprazole is a proton pump inhibitor which reduces gastric acid secretion = through=20 inhibition of H+/K+-ATPase in gastric parietal=20 cells. By inhibiting the functioning of this enzyme, the drug = prevents=20 formation of gastric acid.
[edit]=20 Clinical use
Main article: Proton = pump=20 inhibitor
[edit]=20 Use in Helicobacter pylori=20 eradication
Esomeprazole is combined with the antibiotics clarithromycin = and amoxicillin (or metronidazole) = in the=20 10-day eradication triple therapy for Helicobacter=20 pylori. Infection by H. pylori is the causative factor in = the=20 majority of peptic and duodenal=20 ulcers.
[edit]=20 Evidence of efficacy
AstraZeneca claims that esomeprazole provides improved efficacy, in = terms of=20 stomach acid control, over racemic omeprazole. Many health professionals = have=20 expressed the view that this improvement in efficacy is due to the dose = of=20 esomeprazole recommended for therapy rather than any superiority of = esomeprazole=20 per se.
An alternative rationale suggested for the use of esomeprazole was = the=20 reduction in interindividual variability in efficacy. However the = clinical=20 advantage of this hypothesis has not thoroughly been tested in = large-scale=20 trials.[Somogyi=20 2004]
Given the large difference in cost between all other proton pump = inhibitors=20 and that of Prilosec-OTC (equivalent to omeprazole 20mg), many = physicians=20 recommend a trial of over-the-counter products before beginning more = extensive=20 therapies and testing.





[edit]=20 Dosage forms
Esomeprazole is available as delayed-release capsules in the United = States or=20 as delayed release tablets in Australia and Canada (containing = esomeprazole=20 magnesium) in strengths of 20 mg and 40 mg; and as esomeprazole sodium = for intravenous=20 injection/infusion. Oral esomeprazole preparations are enteric-coated,= due to=20 the rapid degradation of the drug in the acidic conditions of the = stomach. This is=20 achieved by formulating capsules using the multiple-unit pellet = system.
=20

40 mg Nexium=C2=AE brand esomeprazole = capsules
[edit]=20 Multiple unit pellet system
Esomeprazole capsules are formulated as a "multiple unit pellet = system"=20 (MUPS). Essentially, the capsule consists of = extremely=20 small enteric-coated granules (pellets) of the esomeprazole formulation = inside=20 an outer shell. When the capsule is immersed in an aqueous solution, as = happens=20 when the capsule reaches the stomach, water enters the capsule by osmosis. The=20 contents swell from water absorption causing the shell to burst, = releasing the=20 enteric-coated granules. For most patients, the multiple-unit pellet = system is=20 of no advantage over conventional enteric-coated preparations. Patients = for=20 which the formulation is of benefit include those requiring nasogastric = tube=20 feeding and those with difficulty swallowing (dysphagia).
The granules are manufactured in a fluid=20 bed system with small sugar spheres as the starting material. The = sugar=20 spheres are sequentially spray-coated with a suspensi= on=20 containing esomeprazole, a protective layer to prevent degradation of = the drug=20 in manufacturing, an enteric coating and an outer layer to reduce = granule=20 aggregation. The granules are mixed with other inactive excipients and = compressed into=20 tablets. Finally, the tablets are film-coated to improve the stability = and=20 appearance of the preparation.
[edit]=20 Financial impact
Between the launch of esomeprazole in 2001 and 2005, the drug has = netted=20 AstraZeneca about $14.4 billion.[1]<= /P>



[edit]=20 Controversy
There has been some controversy about AstraZeneca's = behaviour in=20 creating, patenting and marketing of the drug. Critics allege that the = drug's=20 successful predecessor Omeprazole is a = mixture of=20 two mirror-im= aged=20 molecules (esomeprazole and romeprazole), and that the company was = trying to=20 "evergreen" its patent by patenting the pure esomeprazole and = aggressively=20 marketing to doctors[1] that it is more effective than the = mixture,=20 claiming that romeprazole has no beneficial effects on the patient. = However, in=20 the acidic environment of the parietal cells = both=20 esomeprazole and romeprazole are converted to the same active drug which = stops=20 the gastric acid production.
Dr.=20 Marcia Angell, former Editor in Chief of the New England Journal of=20 Medicine, spoke at Harvard = Medical=20 School to a German magazine on August 16, 2007 and accused = AstraZeneca's=20 scientists of deceptively doctoring their comparative studies such that = the=20 difference to Omeprazole would look larger, providing a marketing = advantage=20 [2]. For more information, see AstraZeneca's=20 article.
[edit]=20 References
• <= SUP>Lind=20 2004 Lind, T.;=20 Rydberg L., Kyleback A., Jonsson A., Andersson T., Hasselgren T., = Holmberg J.,=20 Rohss K. (July 2000). "Esomeprazole provides improved acid control vs. = omeprazole In patients with symptoms of gastro-oesophageal reflux = disease.".=20 Alimentary=20 pharmacology & therapeutics 14 (7): 861=E2=80=93867. PMID = 10886041.=20 Retrieved on 2006-12-02. =20
• Gladwell, = Malcolm.=20 "High Prices: How to think about prescription = drugs.", A=20 Critic At Large, The New = Yorker, October=20 25, 2004. Retrieved on 2006-12-02. =20 This article describes AstraZeneca's strategy for developing Nexium = as a=20 follow-on for Losec as the latter approached patent expiry. =
[edit]=20 Notes
1. ^<= /B> =20 Gladwell, Malcolm (October 25, 2004). "High Prices: How to think about prescription = drugs". The=20 New Yorker. Verified availability August 19, 2007.=20
2. ^= =20 Grill, Markus and Hansen, Hans: "Vorsicht, Pharma! Wie die Industrie = =C3=84rzte=20 manipuliert und Patienten t=C3=A4uscht." ('Caution, Pharma! How the = industry=20 manipulates physicians and deceives patients.') Published in the = 16.08.2007=20 issue of the magazine "Der = Stern"=20 (Germany; pp. 100-107). Available as an e-paper here. }}=20
1. ^ = Financial=20 impact information: 2005, $4.6 billion; 2004, $3.9 billion; 2003, $3.3 billion; 2002, $2 billion; 2001, launch and $580 million