esomeprazole, Nexium
Esomeprazole 40 mg i.v. provides faster and more effective intragastric acid control than pantoprazole 40 mg i.v.: results of a randomized study.

Wilder-Smith CH, Rohss K, Bondarov P, Hallerback B, Svedberg LE, Ahlbom H.

Gastroenterology Group Practice, GI Physiology Laboratory, Berne, Switzerland. cws ggp.ch

BACKGROUND: Oral esomeprazole 40 mg provides greater acid control than oral pantoprazole 40 mg. AIM: To compare the effects on intragastric acid control of esomeprazole 40 mg administered intravenously with pantoprazole 40 mg intravenously. METHODS: Healthy Helicobacter pylori-negative male and female subjects were enrolled into this single-centre, open, randomized, two-way crossover study. Esomeprazole 40 mg intravenously and pantoprazole 40 mg intravenously were administered as 15-min infusions once daily at 09:00 hours for 5 days. Continuous 24-h intragastric pH monitoring was carried out at baseline and on days 1 and 5. RESULTS: pH-data were available for all 25 subjects who completed the study. Esomeprazole 40 mg intravenously resulted in 8.3 and 13.9 h with an intragastric pH > 4 on days 1 and 5 compared with 5.3 and 9.0 h, respectively for pantoprazole 40 mg intravenously (day 1: P < 0.001, day 5: P < 0.0001). During the first 4 h of dosing on day 1 corresponding values were 1.7 and 0.6 h respectively (P < 0.0001). A mean median pH above 4 on day 5 was only attained with esomeprazole 40 mg intravenously. CONCLUSIONS: Once-daily dosing with esomeprazole 40 mg intravenously provides faster and more pronounced intragastric acid control than pantoprazole 40 mg intravenously.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15569112&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Do physicians correctly assess patient symptom severity in gastro-oesophageal reflux disease?

Fallone CA, Guyatt GH, Armstrong D, Wiklund I, Degl'Innocenti A, Heels-Ansdell D, Barkun AN, Chiba N, Zanten SJ, El-Dika S, Austin P, Tanser L, Schunemann HJ.

Division of Gastroenterology, McGill University Health Center, Montreal, QC, Canada. carlo.fallone mcgill.ca

BACKGROUND: The accuracy of physicians' assessment of the severity of gastro-oesophageal reflux disease is unclear. AIM: To correlate physician and patient assessment of gastro-oesophageal reflux disease severity and its response to treatment. METHODS: Adult uninvestigated gastro-oesophageal reflux disease patients (n = 217) completed symptom and health-related quality of life questionnaires at baseline and after treatment with esomeprazole 40 mg p.o. daily. Pearson coefficients quantified correlations between physician assessments and patient responses. RESULTS: At baseline, the strongest correlations were heartburn severity (0.31), overall symptom severity (0.44) and a domain of the quality of life in reflux and dyspepsia questionnaire (0.31) (P < 0.001). Correlations of change with treatment were greater than baseline correlations: heartburn (0.39), overall symptoms (0.50) and global rate of change -- stomach problems (0.72, all P < 0.001). The mean difference between the physicians' assessment of change and the patients' global rating of change was 0.20 (95% confidence intervals: 0.10-0.29) with physicians overestimating benefit. CONCLUSIONS: Correlations were often significant, although weak to moderate and better with symptom severity than with health-related quality of life instruments as well as with change after therapy than at baseline. Increasing attention to health-related quality of life may help physicians better understand patients' experience. In clinical trials, treatment success should be assessed by the patient as well as the physician.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15569119&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
A pharmacokinetic study comparing single and repeated oral doses of 20 mg and 40 mg omeprazole and its two optical isomers, S-omeprazole (esomeprazole) and R-omeprazole, in healthy subjects.

Hassan-Alin M, Andersson T, Niazi M, Rohss K.

Experimental Medicine, AstraZeneca R & D Molndal, 43183, Molndal, Sweden. mohammed.hassan-alin astrazeneca.com

OBJECTIVE: To investigate the pharmacokinetics of S-omeprazole (esomeprazole), R-omeprazole and racemic omeprazole following single and repeated oral doses of 20 mg and 40 mg of each compound in healthy male and female subjects. METHODS: In an open, randomised, three-way, cross-over study, 12 subjects received 20 mg and another 12 subjects received 40 mg S-omeprazole, R-omeprazole and racemic omeprazole as oral solutions once daily for 5 days, separated by washout periods of at least 10 days. Blood samples were taken for analysis pre-dose and at selected time points during a 12-h period following drug administration on study day 1 and day 5. Pharmacokinetic parameters of S-omeprazole, R-omeprazole, racemic omeprazole and the two main metabolites (5-hydroxy and sulphone) were calculated using non-compartmental analysis. RESULTS: Following the 20-mg dose of each compound, values of the total area under the plasma concentration-time curve (AUC) were 1.52, 0.62 and 1.04 micromol h/l for S-omeprazole, R-omeprazole and racemic omeprazole, respectively, on day 1. Respectively, AUC values on day 5 were 2.84, 0.68 and 1.63 micromol h/l. Corresponding values after the 40-mg doses were 3.88, 1.39 and 2.44 micromol h/l on day 1 and 9.32, 1.80 and 5.79 micromol h/l on day 5. CONCLUSION: Treatment with S-omeprazole (esomeprazole; 20 mg and 40 mg) resulted in higher AUC values than with either R-omeprazole or racemic omeprazole after both single and repeated doses due to a lower metabolic rate of S-omeprazole than R-omeprazole and, consequently, racemic omeprazole. S-Omeprazole, R-omeprazole and the racemate were well tolerated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15578172&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Treatment with proton pump inhibitors in acute non-variceal upper gastrointestinal bleeding: a meta-analysis.

Khuroo MS, Khuroo MS, Farahat KL, Kagevi IE.

Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. khuroo yahoo.com

Medical therapy is an attractive adjuvant to endoscopic treatment in upper gastrointestinal (UGI) bleeding. This review aims to assess the treatment effects of proton pump inhibitor (PPI) therapy in acute non-variceal UGI bleeding. Outcome measures evaluated were further bleeding, surgery, all-cause deaths, ulcer deaths and non-ulcer deaths. We searched MEDLINE (1966-2002) and EMBASE (1974-2002) using the terms 'gastrointestinal hemorrhage', 'peptic ulcer hemorrhage', 'proton pump inhibitor', 'omeprazole', 'pantoprazole', 'lansoprazole', 'rabeprazole' and 'esomeprazole'. The search was extended to the Cochrane controlled trials registry database, published abstracts from five international gastroenterology conferences, manufacturers of PPI, known contacts and bibliographies from each full-length published report. We included trials published in English and non-English languages. Eligible studies were randomized controlled trials that compared the treatment effects of PPI therapy with placebo or H2 receptor antagonists in patients with acute non-variceal UGI bleeding. Of the 175 articles screened, 26 controlled trials including 4670 subjects (2317 in treatment arm and 2353 in control arm) were analyzed. The methodology, population, intervention, and outcomes of each selected trial were evaluated using duplicate independent review. Disagreements were resolved by consensus. PPI therapy significantly reduced rates of further bleeding (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.40-0.57) and surgery (OR, 0.61; 95% CI, 0.48-0.76). All-cause deaths were unaffected (OR, 1.02; 95% CI, 0.76-1.37). Ulcer deaths showed a significant reduction (OR, 0.58; 95% CI, 0.35-0.96), while non-ulcer deaths showed a significant increase (OR, 1.60; 95% CI, 1.06-2.41) in the PPI therapy group. Sensitivity analysis of 22 trials published in peer-reviewed journals, 10 trials with double-blind design and 19 trials with high quality score and 22 trials using omeprazole in the treatment group showed results similar to those seen in the analysis of all 26 trials, confirming the stability of the conclusions. Subgroup analysis revealed that summary outcome measures were not influenced by control group therapy (placebo vs H2 receptor antagonists) or the use of prior endoscopic treatment to achieve hemostasis (given vs not given). However, the summary treatment effects for further bleeding and need for surgery were significant in only those trials enrolling patients with peptic ulcers having high risk for rebleeding and not in those trials enrolling patients with all causes of UGI bleeding. The summary treatment effects for further bleeding and need for surgery were significant in trials using intravenous as well as oral PPI. However, summary OR for all-cause deaths and non-ulcer deaths in trials using intravenous PPI were higher in the treatment group and not in trials using oral PPI. This raised the possibility of intravenous PPI-therapy-associated non-ulcer deaths in high-risk patients. PPI therapy in acute non-variceal UGI bleeding reduced rates of further bleeding, surgery and deaths caused by ulcer complications. However, non-ulcer deaths were increased. The overall mortality was unaffected. PPI therapy is useful only in a selected group of patients with acute non-variceal UGI bleeding, namely those with peptic ulcers having endoscopic high-risk stigmata for rebleeding.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15610441&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Dual-probe 24-hour ambulatory pH monitoring for diagnosis of laryngopharyngeal reflux.

Issing WJ, Karkos PD, Perreas K, Folwaczny C, Reichel O.

Department of Otolaryngology, The Freeman Hospital, Newcastle Upon Tyne NE7 7DN, UK. wolfgang.issing nuth.northy.nhs.uk

BACKGROUND: Patients with gastroesophageal reflux disease may suffer from a variety of symptoms from the upper aerodigestive tract. The objective of this study was to determine the impact of dual-probe 24-hr pH monitoring in the diagnosis of reflux-related otolaryngological disorders. METHODS: Twenty-two patients with symptoms such as chronic cough, globus pharyngeus, heartburn, dysphonia and burning sensation of the tongue underwent a complete ear, nose and throat examination, 24-hr dual-probe pH monitoring, and oesophago-gastro-duodenoscopy. RESULTS: pH monitoring revealed gastroesophageal (distal) reflux in all patients and pharyngeal (proximal) reflux in 21 patients. Treatment consisted of a proton pump inhibitor (esomeprazole). Within 4 weeks 68 per cent of patients had no laryngopharyngeal symptoms; within 8 weeks 95 per cent of patients were symptom-free. CONCLUSIONS: Patients with atypical reflux symptoms such as hoarseness, globus sensation or throat-clearing responded well to anti-reflux treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15638969&dopt=Abstract esomeprozole Nexium