esomeprazole, Nexium
Risk factors for the severity of erosive esophagitis in Helicobacter pylori-negative patients with gastroesophageal reflux disease.

El-Serag HB, Johanson JF.

Gastroenterology and Health Services Research, Houston VA Medical Center, Baylor College of Medicine, Texas 77030, USA. hasheme bcm.tmc.edu

BACKGROUND: The risk factors for the varying grades of erosive esophagitis (EE) severity could be better understood. For that reason. we evaluated the risk factors associated with EE in patients with gastroesophageal reflux disease. METHOD: We determined the presence and severity of EE (using the Los Angeles Classification) in patients with negative serology Helicobacterpylori who underwent esophagogastroduodenoscopy as part of screening in four prospective, multicenter, randomized, double-blind comparative trials of once-daily esomeprazole and omeprazole for the acute healing of erosive esophagitis. We also examined the baseline characteristics of enrolled patients, and identified risk factors for severe disease using a multivariable logistic regression model. RESULTS: Erosive esophagitis was documented in 6709 patients of a total of 10,294 patients who underwent endoscopy: of these. 34% had grade A. 39% had grade B. 20% had grade C. and 7% had grade D disease. The majority of patients were male (61%) and Caucasian (93%) with a mean age of 46 years. In the regression model, the following were significant independent risk factors for severe (grades C and D) versus mild erosive esophagitis (grades A and B): severe heartburn (adjusted odds ratio 1.79); prolonged heartburn > 5 years in duration (1.16); obesity (1.21); the presence of hiatus hernia (2.13); male gender (1.97); and Caucasian ethnicity (1.53). CONCLUSION: In this large sample of patients with predominantly H. pylori-negative gastroesophageal reflux disease, risk factors for severe erosive esophagitis were the duration and severity of heartburn, and obesity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12229963&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Intravenous esomeprazole.

Keating GM, Figgitt DP.

Adis International Limited, Mairangi Bay, Auckland, New Zealand. demail adis.co.nz

The proton pump inhibitor esomeprazole comprises the S-isomer of omeprazole. An intravenous formulation of the drug has been developed for use in patients not able to take oral drugs. The level of gastric acid control was similar with intravenous and oral esomeprazole in two studies in healthy volunteers receiving 20 or 40 mg once daily for 5 days. In addition, a similar level of gastric acid control occurred with intravenous esomeprazole 40 mg administered by infusion or injection once daily for 10 days. In healthy volunteers, intravenous esomeprazole provided faster and more effective gastric acid control than intravenous pantoprazole (40 mg once daily for 5 days). In addition, control of basal and pentagastrin-stimulated gastric acid secretion was better with intravenous esomeprazole 40 mg than with intravenous omeprazole 40 mg (single-dose study). Healing rates at 4 weeks were approximate, equals 80% in a well designed study in patients with erosive oesophagitis (n = 246) who received esomeprazole 40 mg once daily intravenously (by injection or infusion) or orally. Intravenous therapy was administered for the first week, after which all patients received oral esomeprazole. Intravenous esomeprazole was generally well tolerated in patients with erosive oesophagitis, with a tolerability profile similar to that of the oral formulation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15059043&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
[Chiral switch, a successful way for developing drugs: example of esomeprazole]

[Article in German]

Creutzfeldt W.

Zentrum Innere Medizin, Georg-August-Universitat Gottingen.

About 25% of common drugs are racemates, i.e. mixtures of their optical or spatial isomers (stereoisomers or enantiomers). Frequently the enantiomers differ in their pharmacokinetics, pharmacodynamics, drug interactions and side effects. Therefore, the pharmaceutical industry, pharmacologists and clinicians are increasingly interested in the development of enantiomers as drugs. Since advances in synthetic and analytical chemistry have provided the tools to produce stereoisomeric drugs, also the authorities recommend and support chiral switch. As example for the therapeutic gain the recent studies with esomeprazole, the first isomeric protonpump inhibitor (iPPI) are summarized and discussed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11132535&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Pharmacokinetics of esomeprazole after oral and intravenous administration of single and repeated doses to healthy subjects.

Hassan-Alin M, Andersson T, Bredberg E, Rohss K.

Experimental Medicine, AstraZeneca Research and Development Molndal, Sweden. mohammed.hassan-alin astrazeneca.com

OBJECTIVE: To study the pharmacokinetics of esomeprazole, one of the optical isomers of omeprazole, after 20 mg or 40 mg single and repeated oral and intravenous administration to healthy subjects. The main metabolites of esomeprazole were also assessed after the 40-mg oral dose. METHODS: In two separate studies, 16 healthy male subjects and 16 healthy male and female subjects received intravenous doses of 20 mg and 40 mg esomeprazole, respectively, on the first investigation day. After a washout period of 5-14 days, the same doses (20 mg as a solution and 40 mg as a capsule) were given orally for 5 days and then again intravenously on day 6. Blood samples for determination of esomeprazole and its metabolites were collected 12 h or 24 h post-dose and were analysed using normal-phase liquid chromatography with ultraviolet (UV) detection. Pharmacokinetic parameters of esomeprazole and its metabolites were estimated using non-compartmental analysis. Geometric means and ratios of the geometric means together with 95% confidence intervals (CI) of the pharmacokinetic parameters were calculated using analysis of variance (ANOVA). RESULTS: Plasma clearance (CL) of esomeprazole decreased from 22 l/h to 16 l/h and from 17 l/h to 9 l/h following repeated dosing of 20 mg and 40 mg, respectively. Total area under the plasma concentration-time curve (AUC) increased (from 1.34 micromol x h/l to 2.55 micromol x h/l) with absolute bioavailability (F) being 50% on day 1 and 68% on day 5 after the 20-mg oral dose. AUC increased (from 4.32 micromol x h/l to 11.21 micromol x h/l) with F being 64% on day 1 and 89% on day 5 after the 40-mg oral dose. The plasma levels for esomeprazole sulphone were substantially higher on day 5 than on day 1, while those for 5-hydroxy esomeprazole were marginally higher on day 5 than on day 1 following repeated oral dosing of 40 mg esomeprazole. No side effects attributable to esomeprazole were noticed. CONCLUSION: The increased AUC of esomeprazole with repeated dosing is probably due to a combination of a decreased first-pass elimination and a decreased systemic clearance.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11214773&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Effect of splitting the dose of esomeprazole on gastric acidity and nocturnal acid breakthrough.

Hammer J, Schmidt B.

Abteilung fur Gastroenterologie und Hepatologie, Universitatsklinik fur Innere Medizin IV, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. johann.hammer univie.ac.at

BACKGROUND: Twice-daily dosing is increasingly used to improve gastric acid control, although not all proton-pump inhibitors are more effective when doses are split. Standard dose esomeprazole provides better gastric acid control than other standard dose proton-pump inhibitors. AIMS: To compare the effect of standard dose esomeprazole (1 x 40 mg) with 20 mg b.d. on gastric acidity. METHODS: Thirteen healthy subjects participated in this crossover study, receiving esomeprazole 2 x 20 mg and 1 x 40 mg for 7 days in random order with a washout period of at least 7 days. Gastric 24-h pH was measured on days 1, 2 and 6. RESULTS: Median gastric 24-h pH was higher during 2 x 20 mg esomeprazole on day 2 (P < 0.01), no differences were detected on day 6. Night-time gastric acid suppression was significantly improved by 2 x 20 mg esomeprazole on all study days (P < 0.05). Nocturnal acid breakthrough was observed on all study days in subjects receiving 1 x 40 mg, but in only 85% (first night), 64% (second night), and 45% of subjects (sixth night) with 2 x 20 mg (P < 0.05). CONCLUSION: Splitting the esomeprazole dose improves initial acid suppression, this effect starts at the first night. Maximal benefit is achieved on day 2, while the effect on night-time acid control is detectable during the entire first week of treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15142200&dopt=Abstract esomeprozole Nexium