s-1743 and Zollinger-Ellison-Syndrome

Esomeprazole (Nexium); S-omeprazole) is a single optical isomer proton-pump inhibitor (PPI) approved for the management of reflux oesophagitis, the symptomatic treatment of gastro-oesophageal reflux disease (GORD), the prevention and healing of NSAID-associated gastric ulcer disease (and the prevention of NSAID-associated duodenal ulcers in the UK), the treatment of Helicobacter pylori infection and associated duodenal ulcer disease (and prevention of relapse of H. pylori-associated peptic ulcers in the UK), and the treatment of Zollinger-Ellison syndrome (and other hypersecretory syndromes in the US).Once-daily oral esomeprazole 40 mg demonstrates greater antisecretory activity than other PPIs. Overall, in well designed clinical studies of 4 weeks' to 6 months' duration in patients with GORD, esomeprazole had similar or better efficacy than other agents. In patients requiring ongoing treatment with NSAIDs, co-therapy with once-daily esomeprazole 20 or 40 mg achieved relief of gastrointestinal symptoms or prevented ulcer occurrence, more effectively than placebo. Esomeprazole was also better than ranitidine 150 mg twice daily in healing NSAID-associated gastric ulcers. In addition, the drug has demonstrated efficacy as part of a triple-therapy regimen for the eradication of H. pylori infection, the healing of H. pylori associated duodenal ulcers and the prevention of relapse of gastric ulcers. Esomeprazole also effectively treated patients with Zollinger-Ellison syndrome. Esomeprazole is generally well tolerated with an adverse-event profile similar to that of other PPIs. Thus, the efficacy and tolerability of esomeprazole for the management of GORD and H. pylori eradication remains undisputed, and the data support its use for the first-line treatment of NSAID-associated gastric ulcer disease and Zollinger-Ellison syndrome.

Topics: Adult; Anti-Ulcer Agents; Duodenal Ulcer; Esomeprazole; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Omeprazole; Proton Pump Inhibitors; Stomach Ulcer; Zollinger-Ellison Syndrome

Pantoprazole (Protonix) is an irreversible proton pump inhibitor (PPI) that reduces gastric acid secretion. In combination with two antimicrobial agents (most commonly metronidazole, clarithromycin or amoxicillin) for 6-14 days, pantoprazole 40 mg twice daily produced Helicobacter pylori eradication rates of 71-93.8% (intent-to-treat [ITT] or modified ITT analysis) in patients without known antibacterial resistance. Pantoprazole-containing triple therapy was at least as effective as omeprazole- and similar in efficacy to lansoprazole-containing triple therapy in large trials. In the treatment of moderate to severe gastro-oesophageal reflux disease (GORD), oral pantoprazole 40 mg/day was as effective as other PPIs (omeprazole, omeprazole multiple unit pellet system, lansoprazole and esomeprazole) and significantly more effective than histamine H(2)-antagonists. Pantoprazole 20 mg/day provided effective mucosal healing in patients with GORD and mild oesophagitis. Intravenous pantoprazole 40 mg/day can be used in patients who are unable to take oral medication. Oral pantoprazole 20-40 mg/day for up to 24 months prevented relapse in most patients with healed GORD. According to preliminary data, oral pantoprazole 20 or 40 mg/day was effective at healing and preventing non-steroidal anti-inflammatory drug (NSAID)-related ulcers, and intravenous pantoprazole was at least as effective as intravenous ranitidine in preventing ulcer rebleeding after endoscopic haemostasis. Oral or intravenous pantoprazole up to 240 mg/day maintained target acid output levels in most patients with hypersecretory conditions, including Zollinger-Ellison syndrome. Oral and intravenous pantoprazole appear to be well tolerated in patients with acid-related disorders in short- and long-term trials. Tolerability with oral pantoprazole was similar to that with other PPIs or histamine H(2)-antagonists in short-term trials. Formal drug interaction studies have not revealed any clinically significant interactions between pantoprazole and other agents. In conclusion, pantoprazole is an effective agent in the management of acid-related disorders. As a component of triple therapy for H. pylori eradication and as monotherapy for the healing of oesophagitis and maintenance of GORD, pantoprazole has shown similar efficacy to other PPIs and greater efficacy than histamine H(2)-antagonists. Limited data suggest that it is also effective in Zollinger-Ellison syndrome and in preventing ulcer rebleeding.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Benzimidazoles; Clinical Trials as Topic; Dose-Response Relationship, Drug; Esomeprazole; Gastroesophageal Reflux; Helicobacter Infections; Humans; Omeprazole; Pantoprazole; Peptic Ulcer; Sulfoxides; Zollinger-Ellison Syndrome

Awareness of important differences in the pharmacological profile of individual optical isomers of chiral drugs led to the development of esomeprazole, the S-isomer of omeprazole, a new pharmacological entity designed to improve the clinical outcome of available proton pump inhibitors in the management of acid-related disorders. The superior acid control achieved by esomeprazole is mainly due to an advantageous metabolism compared with racemate omeprazole, leading to improved bioavailability and to enhanced delivery of the drug to the gastric proton pump.

Topics: Anti-Ulcer Agents; Drug Interactions; Esomeprazole; Humans; Omeprazole; Peptic Ulcer; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Zollinger-Ellison Syndrome

A patient suffering from Zollinger-Ellison was treated with Nexium, but after patent expiry only the costs of generic omeprazol were reimbursed. Generic tablets and capsules, pantoprazol and rabeprazol, were tried without success and finally the pharmacist dispensed Nexium at his own expense. Registered generic drugs have been shown to be bioequivalent with the originator drug within narrow margins. When two batches of the originator are compared, the same requirements are valid. Although the subject has received a lot of negative publicity, meta-analyses on outcome comparison support generic substitution; problems associated with switching can be partially explained by the loss of trust in the treatment, and differences in appearance also cause confusion. Generic prescribing should be encouraged to keep medical treatment affordable; however, in order to prevent the problems described it is desirable to keep to the same product as far as possible. Effective education and patient information are essential if switching is to be successful.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Ulcer Agents; Drugs, Generic; Esomeprazole; Humans; Pantoprazole; Rabeprazole; Treatment Outcome; Zollinger-Ellison Syndrome

Secretin stimulation testing (SST) is used to evaluate patients with hypergastrinemia in the diagnosis of Zollinger-Ellison syndrome. Case series have documented false-positive SST in patients with achlorhydria. This study reviews our experience with SST in hypochlorhydric and achlorhydric patients.. We examined 27 patients with hypochlorhydria or achlorhydria based on a predefined basal acid output (BAO) measurement of less than 5.0 mEq/h who also underwent SST for diagnosis of Zollinger-Ellison syndrome. We report the frequency of false-positive SST results in this setting.. Three hundred thirty patients underwent gastric analysis of which 27 had BAO of less than 5.0 mEq/h and SST conducted. The mean (SD) fasting gastrin level was 247 (304) pg/mL, and the mean (SD) BAO measurement was 1.6 (1.8) mEq/h. Twenty patients were off, and 7 were on antisecretory therapy at time of testing. Four patients had false-positive SST results: 3 with gastric atrophy (BAO = 0 mEq/h) and 1 with drug-induced hypochlorhydria (BAO = 0.5 mEq/hr). These false-positive test results were confirmed by structural and functional imaging studies.. We have identified a 14.8% false-positive rate in SST in patients with hypochlorhydria or achlorhydria. Growing literature has identified severe consequences associated with discontinuing antisecretory treatment for testing; therefore, SST will require interpretation in the setting of gastric acid suppression and needs to be interpreted in this context.

Topics: Achlorhydria; Adolescent; Adult; Aged; Anti-Ulcer Agents; Esomeprazole; False Positive Reactions; Female; Gastric Acid; Gastric Mucosa; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Rabeprazole; Secretin; Sensitivity and Specificity; Stomach; Young Adult; Zollinger-Ellison Syndrome

To evaluate the efficacy and safety of oral esomeprazole in the control of gastric acid hypersecretion in patients with hypersecretory states.. In this 12-month, open-label, multicenter study, acid output (AO) was evaluated at baseline, day 10, and months 3, 6, and 12. The starting dose of esomeprazole was 40 mg or 80 mg twice daily. On day 10, patients with controlled AO were maintained on the same dose, while those with uncontrolled AO had their doses increased (maximum dose 240 mg/day) until control was attained. Esophagogastroduodenoscopy (EGD) was performed at baseline and at 6 and 12 months. Safety and tolerability were assessed throughout the study by EGD, gastric analysis, and adverse events.. Twenty-one patients (19 with Zollinger-Ellison syndrome [ZES], 2 with idiopathic gastric acid hypersecretion [IGH]) completed the study. Of the 20 patients with controlled AO at day 10, 18 (90%) had sustained AO control for the rest of the study. At 12 months, AO was controlled in 14 of 16 patients receiving esomeprazole 40 mg twice daily, in all 4 patients receiving esomeprazole 80 mg twice daily, and in the 1 patient receiving esomeprazole 80 mg 3 times daily. At 6 and 12 months, no patient had endoscopic evidence of mucosal disease. Esomeprazole was well tolerated; 1 patient had a serious adverse event (hypomagnesemia) attributed to treatment that resolved with magnesium supplementation during continued treatment.. Esomeprazole in appropriately titrated doses controls AO over 12 months in patients with hypersecretory states and is well tolerated.

Topics: Adult; Aged; Anti-Ulcer Agents; Esomeprazole; Female; France; Gastric Acid; Humans; Male; Middle Aged; Treatment Outcome; United States; Zollinger-Ellison Syndrome