esomeprazole, Nexium
Efficacy of esomeprazole in controlling reflux symptoms, intraesophageal, and intragastric pH in patients with Barrett's esophagus.

Yeh RW, Gerson LB, Triadafilopoulos G.

Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.

Barrett's esophagus is a metaplastic condition associated with gastroesophageal reflux disease and an increased risk for adenocarcinoma. Acid plays a significant role in the development and progression of Barrett's esophagus and high dose proton pump inhibitor (PPI) therapy is often needed. The aim of this study is to assess the efficacy of esomeprazole, a new potent PPI, on symptom relief and intraesophageal and intragastric acid suppression in patients with Barrett's esophagus (BE). Patients were evaluated by standardized questionnaires and dual sensor 24-h pH monitoring while receiving esomeprazole at a dose (40-80 mg/day) needed for control of symptoms. Analyses of intraesophageal and intragastric pH profiles were then made. Thirteen patients, mostly men, were studied. All tolerated esomeprazole (40-80 mg/day) with good symptom control. Sixty-two percent of patients with BE had abnormal intraesophageal pH profiles despite adequate symptom control on esomeprazole which was associated with significant breakthrough of intraesophageal acid control, particularly at night. Low nocturnal intragastric pH correlated highly with nocturnal intraesophageal acid reflux (P = 0.004) and there was a relative failure of nocturnal intragastric acid control with esomeprazole. A high percentage of patients with BE continue to exhibit pathologic GERD and low intragastric pH despite esomeprazole for reflux symptom control. For an antisecretory treatment aimed at chemoprevention of esophageal adenocarcinoma to be effective, higher PPI dosing confirmed by pH monitoring may be necessary.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14641308&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Relative efficacies of gastric proton-pump inhibitors on a milligram basis: desired and undesired SH reactions. Impact of chirality.

Kromer W.

Dept. of Pharmacology, Byk Gulden, Konstanz, Germany.

Gastric proton-pump inhibitors (PPIs) are prodrugs. Their acid activation at pH 1.0 inside the canaliculus of a parietal cell should be fast relative to their serum elimination rate. Actually, all PPIs display chemical activation half-lives at pH 1.0 of a few minutes at the most, while being eliminated from serum with a half-life of about 1 h. This is the main reason they show similar antisecretory efficacies on a milligram basis. It is in line with about 5% to 15% higher healing rates in GERD, DU and GU when 40 mg is compared to 20 mg of either omeprazole or pantoprazole. The comparably large biological variation between patient samples explains why some studies show statistically significant differences between the two doses, while others do not. However, it would matter to the individual patient if s/he was the one additionally healed by a 40 mg dose within a defined treatment period. Chemical activation of PPI prodrugs is unwanted in weakly acidic tissue compartments such as lysosomes or secretory granules. However, the ratio of the serum elimination half-life (availability at the target) to the chemical activation half-life at a critical pH 5.0 is reversed only with pantoprazole. when compared to pH 1.0 (i.e. the ratio is < 1 at pH 5.0 and > 1.0 at pH 1.0). This is the basis of the high pH selectivity of pantoprazole. In contrast, rabeprazole is activated at pH 5.0 almost as quickly as it is at pH 1.0 and much faster than it is eliminated from serum. This unwanted reactivity of rabeprazole at pH 5.0 does not contribute to the antisecretory action at pH 1.0 and results in poor pH selectivity. Omeprazole and lansoprazole lie in between, as they are activated, at pH 5.0, about as quickly as they are eliminated from serum. The above activation rates refer to room temperature. At 37 degrees C. the activation rates of all PPIs further increase, by about the same factor of between 3 and 4. This renders their differential pH selectivities even more critical for drug safety. Biological consequences have been reported in the literature. It has been claimed that a dose of 40 mg of the S-enantiomer of omeprazole (esomeprazole) results in 10%-15% higher healing rates in GERD patients, compared to 20 mg omeprazole racemate. The same difference is found when the two doses of omeprazole racemate are compared to each other. This is not surprising, as the chiral PPI prodrug is converted by acid into an achiral cyclic sulfenamide which only then reacts with the proton pump. There is therefore no pharmacodynamic argument in favour of any single enantiomer formulation of any PPI. Moreover, potential pharmacokinetic differences between the enantiomers seem to be of little if any importance in the patient.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11768559&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Helicobacter pylori: diseases, tests and treatment.

Vaira U, Gatta L, Ricci C, D'Anna L, Iglioli MM.

Department of Internal Medicine and Gastroenterology, S. Orsola Hospital, University of Bologna, Italy. vairadin med.unibo.it

Gastroduodenal disease associated with Helicobacter pylori infection are reviewed as well as the diagnostic approach. Generally, there are by and large two ways in which a diagnosis of infection by Helicobacter pylori can be made: by using either an invasive or non-invasive procedure. The invasive procedures involve endoscopy and biopsy Biopsy is essential since the mucosa may often appear macroscopically normal but, nevertheless, be inflamed. Once a biopsy is obtained histological examination, culture, polymerase chain reaction, detection of the presence of urease activity can be detected. The non-invasive tests that can be used to diagnose the infection are: serology, detection of labelled metabolic products of urea hydrolysis either in the breath (13CO2, 14CO2), the urine or the blood, detection of Helicobacter pylori antigen in stool specimen. At present, no single test is sufficiently reliable to definitely detect colonisation by Helicobacter pylori, and a combination of two is recommended, if feasible. Choice of the test to be used is not straightforward and relies on a series of situations, i. e., clinical setting and local expertise and availability, that the clinician must consider to obtain the best diagnostic yeld. The challenge of Helicobacter pylori eradication is not very easy to obtain. The possible scenario and the use of a new proton pump inhibitor (esomeprazole) are reviewed and discussed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11838615&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Cost effectiveness of proton pump inhibitors in gastro-oesophageal reflux disease without oesophagitis: comparison of on-demand esomeprazole with conventional omeprazole strategies.

Wahlqvist P, Junghard O, Higgins A, Green J.

AstraZeneca R&D Molndal, Sweden. peter.wahlqvist astrazeneca.com

OBJECTIVES: To evaluate the cost effectiveness of on-demand treatment with esomeprazole 20mg compared with two alternative omeprazole treatment strategies for the long-term management of patients with gastro-oesophageal reflux disease (GORD) without oesophagitis. DESIGN: A simple Markov model was designed to compare the cost effectiveness of on-demand esomeprazole 20mg therapy for 6 months with a strategy consisting of intermittent 4-week acute treatment courses of omeprazole 20mg once daily or a strategy consisting of continuous omeprazole treatment (20mg once daily) following acute treatment of first relapse while on no drug treatment (a commonly used conventional care strategy). Relapse probabilities were based on pooled results from two 6-month placebo-controlled clinical studies of on-demand esomeprazole 20mg treatment in patients with GORD without oesophagitis and on results from a GORD study with a 6-month untreated follow-up. The expected number of relapses per patient was used as the effectiveness measure. SETTING AND PERSPECTIVE: Patient management assumptions were based on a UK physician survey. The cost-effectiveness analysis considered UK direct medical costs from the perspective of the National Health Service. RESULTS: The pooled analysis showed that after 6 months treatment, 90% of patients could control symptoms effectively with on-demand esomeprazole 20mg. The expected number of relapses per patient was estimated at 0.10 for on-demand esomeprazole, 0.57 to 1.12 for intermittent omeprazole and 0.47 to 0.75 for conventional omeprazole treatment. The esomeprazole strategy incurred considerably lower direct medical costs (16 to 61%) than either omeprazole strategy. CONCLUSION: On-demand treatment with esomeprazole 20mg is cost effective compared with two alternative omeprazole treatment strategies in patients with GORD without oesophagitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11950383&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Cost effectiveness of esomeprazole compared with omeprazole in the acute treatment of patients with reflux oesophagitis in the UK.

Wahlqvist P, Junghard O, Higgins A, Green J.

AstraZeneca R&D Molndal, Sweden. peter.wahlqvist astrazeneca.com

BACKGROUND: Clinical studies have demonstrated that esomeprazole is superior to omeprazole for the acute treatment of reflux oesophagitis. OBJECTIVE: To compare the cost effectiveness of esomeprazole 40mg once daily with omeprazole 20mg once daily in patients with reflux oesophagitis. METHODS: Pooled data were used from three 8-week clinical trials comparing the efficacy and safety of esomeprazole 40mg once daily and omeprazole 20mg once daily for the acute treatment of reflux oesophagitis. A simple decision analysis model, using UK direct medical costs, compared the cost effectiveness of the two treatments. Healing probabilities derived from the clinical studies using the Life Table method were used to estimate the effectiveness and cost of treating 100 patients with reflux oesophagitis. Patient management assumptions were based on a clinical management survey involving 25 UK physicians. PERSPECTIVE: UK National Health Service. RESULTS: After 4 weeks' therapy, the Life Table estimated the oesophageal healing rate to be 77.7% in esomeprazole 40mg once-daily recipients (n = 2446), compared with 67.6% in omeprazole 20mg once-daily recipients (n = 2431; p < 0.001). The corresponding values after 8 weeks' treatment were 93.4% and 86.2%, respectively (p < 0.001). The model predicted that when considering healing probabilities over 8 weeks, esomeprazole 40mg once daily produced total direct cost savings of pound1290 (14%) when compared with omeprazole 20mg once daily. When considering the cost of treating patients who had failed treatment (defined as patient not healed as assessed by endoscopy) after 8 weeks, the cost advantage for esomeprazole was even greater. CONCLUSION: Esomeprazole 40mg once daily is cost effective compared with omeprazole 20mg once daily in the acute treatment of patients with reflux oesophagitis; esomeprazole provides greater effectiveness at a lower cost.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11950384&dopt=Abstract esomeprozole Nexium