omeprazole, Prilosec
Depletion of enterochromaffin-like cell histamine increases histidine decarboxylase and chromogranin A mRNA levels in rat stomach by a gastrin-independent mechanism.

Andersson K, Lindstrom E, Chen D, Monstein HJ, Boketoft A, Hakanson R.

Dept. of Pharmacology, University of Lund, Sweden.

BACKGROUND: Gastrin activates histidine decarboxylase (HDC) and increases HDC and chromogranin A (CGA) mRNA levels in histamine-producing enterochromaffin-like (ECL) cells in the rat stomach. We have studied how histamine depletion by subcutaneous infusion of the HDC inhibitor alpha-fluoromethyl-histidine (alpha-FMH) affects how ECL cells respond to hypergastrinemia in terms of HDC and CGA mRNA levels. METHODS: In one experiment rats received alpha-FMH for 24 h. In another experiment rats received alpha-FMH, omeprazole (perorally), or a combination of the two drugs for 10 days. In a third experiment antrectomized rats were treated with alpha-FMH for 48 h. The circulating gastrin level, oxyntic mucosal histamine concentration, HDC activity, and HDC and CGA mRNA levels were determined. RESULTS: alpha-FMH for 24 h increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration. alpha-FMH for 10 days increased the serum gastrin concentration twofold. alpha-FMH + omeprazole resulted in the same serum gastrin concentration as after omeprazole alone (eightfold increase). HDC mRNA levels were higher after alpha-FMH + omeprazole than after omeprazole alone. alpha-FMH alone induced an HDC mRNA level that was similar in magnitude to that observed after omeprazole, although the serum gastrin concentration after alpha-FMH was much lower. In antrectomized rats alpha-FMH increased the HDC and CGA mRNA levels without increasing the serum gastrin concentration. CONCLUSION: ECL-cell histamine depletion will increase mRNA levels for HDC and CGA by a gastrin-independent mechanism, possibly involving abolished histamine autofeedback inhibition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8898415&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
A prospective study of simplified omeprazole suspension for the prophylaxis of stress-related mucosal damage.

Phillips JO, Metzler MH, Palmieri MT, Huckfeldt RE, Dahl NG.

Department of Surgery, University of Missouri-Columbia 65212, USA.

OBJECTIVES: To determine the efficacy, safety, and cost of simplified omeprazole suspension in mechanically ventilated critically ill patients who have at least one additional risk factor for stress-related mucosal damage. DESIGN: Prospective, open-label study. SETTING: Surgical intensive care and burn unit at a university tertiary care center. PATIENTS: Seventy-five adult, mechanically ventilated patients with at least one additional risk factor for stress-related mucosal damage. INTERVENTIONS: Patients received 20 mL of simplified omeprazole suspension (containing 40 mg of omeprazole) initially, followed by a second 20-mL dose 6 to 8 hrs later, then 10 mL (20 mg) daily. Simplified omeprazole suspension was administered through a nasogastric tube, followed by 5 to 10 mL of tap water. The nasogastric tube was clamped for 1 to 2 hrs after each administration. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was clinically significant gastrointestinal bleeding determined by endoscopic evaluation, nasogastric aspirate examination, or heme-positive coffee ground material that did not clear with lavage, which was associated with at least a 5% decrease in hematocrit. Secondary efficacy measures were gastric pH measured 4 hrs after omeprazole was first administered, mean gastric pH after omeprazole was started, and the lowest gastric pH during omeprazole therapy. Safety-related outcomes included the occurrence rate of adverse events and pneumonia. No patient experienced clinically significant upper gastrointestinal bleeding after receiving omeprazole suspension. The 4-hr postomeprazole mean gastric pH was 7.1, the mean gastric pH after starting omeprazole was 6.8, and the mean lowest pH after starting omeprazole was 5.6. The occurrence rate of pneumonia was 12%. No patient in this high-risk population experienced an adverse event or a drug interaction that was attributable to omeprazole. CONCLUSIONS: Simplified omeprazole suspension prevented clinically significant upper gastrointestinal bleeding and maintained gastric pH of > 5.5 in mechanically ventilated critical care patients without producing toxicity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8917027&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Cost effectiveness of medical versus surgical treatment in patients with severe or refractory gastroesophageal reflux disease in the Netherlands.

Van Den Boom G, Go PM, Hameeteman W, Dallemagne B, Ament AJ.

Dept. of Health Economics, University of Limburg, Maastricht, Netherlands.

BACKGROUND: For a significant number of patients with severe or refractory gastroesophageal reflux disease, maintenance treatment with omeprazole and reflux surgery (Nissen fundoplication) are alternative treatment options. In this study maintenance treatment with omeprazole is compared with open and laparoscopic Nissen fundoplication from a health-economic perspective. METHODS: Meta-analysis of published articles to assess effectiveness and simple decision-analytic techniques to combine costs and effects are used. Findings and assumptions are submitted to sensitivity analysis. RESULTS: It is estimated that it costs approximately 1880 Dutch guilders to initially heal a patient with severe or refractory esophagitis with 40 mg omeprazole daily. When medical maintenance therapy was compared with surgery, it appeared that medical maintenance therapy with omeprazole (20-40 mg daily) for a prolonged period of time (more than 4 years) is less cost effective than a Nissen procedure. It is estimated that a laparoscopic Nissen will shift this so-called break-even point towards 1.4 years, mainly due to a shorter hospital stay. CONCLUSIONS: Although caution is required in drawing conclusions, it appears that replacing treatment with (laparoscopic) Nissen fundoplications in these patients might lead to substantial savings.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8927933&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Metabolic interactions of the proton-pump inhibitors lansoprazole, omeprazole and pantoprazole with other drugs.

Meyer UA.

Department of Pharmacology, Biozentrum of the University of Basel, Switzerland.

PURPOSE: To analyse the metabolism of the proton-pump inhibitors lansoprazole, omeprazole and pantoprazole by cytochrome P450 (CYP) enzymes, and to assess the consequences for drug-drug interactions. RESULTS OF DATA ANALYSIS: Lansoprazole, omeprazole and pantoprazole are extensively metabolized by several human cytochromes P450, most prominently by mephenytoin hydroxylase (CYP2C19) and nifedipine hydroxylase (CYP3A4). Only pantoprazole is also metabolized to a significant extent by a conjugating enzyme, a cytosolic sulfotransferase. The substrates and inhibitors of CYP2C19 and CYP3A4 and the known genetic polymorphism of CYP2C19 explain some but not all of the interactions of lansoprazole, and particularly the interactions of omeprazole with carbamazepine, diazepam, phenytoin and theophylline or caffeine. Both lansoprazole and omeprazole apparently also induce cytochromes P450 such as CYP1A2. This effect appears at lower doses of omeprazole in poor metabolizers of omeprazole. Of these three drugs, pantoprazole has by far the lowest potential for interactions, both in vitro (in microsomal studies) and in volunteer studies. CONCLUSIONS: Proton-pump inhibitors interact with and are metabolized by several human cytochromes P450, but only pantoprazole is also metabolized by a sulfotransferase. This may partly explain why, in this group of proton-pump inhibitors, pantoprazole has the lowest potential for interactions with other drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8930576&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Duodenogastric reflux causes growth stimulation of foregut mucosa potentiated by gastric acid blockade.

Wetscher GJ, Hinder RA, Kretchmar D, Stinson R, Perdikis G, Smyrk T, Klingler PJ, Adrian TE.

Department of Surgery, Creighton University, Omaha, Nebraska, USA.

We investigated whether duodenogastric reflux (DGR) together with gastroesophageal reflux causes growth stimulation of the foregut mucosa and if additional gastric acid suppression enhances the effect of DGR. DGR was induced in rats using a split gastroenterostomy. A cardiomyotomy was performed across the gastroeophageal junction in order to enhance reflux into the esophagus. DGR rats were divided into six subgroups: DGR, DGR + truncal vagotomy, DGR + omeprazole, DGR + gastrin receptor blockade, DGR + omeprazole + gastrin receptor blockade, and DGR + gastrin. Two sham groups, one with and one without omeprazole treatment, served as controls. DGR significantly increased the weight and DNA content of the esophageal and gastric mucosa, which was further enhanced by vagotomy or omeprazole. Histology revealed foveolar hyperplasia in the stomach and esophageal mucosal hyperplasia in these groups. In addition, severe esophagitis was found in the DGR group receiving omeprazole. Omeprazole without DGR had no growth-stimulating effect on the foregut mucosa. DGR-induced growth stimulation was accompanied by hypergastrinemia. Increased growth in the stomach but not the esophagus was inhibited by gastrin receptor blockade. Gastrin administration did not result in enhancement of DGR-induced growth stimulation of the foregut mucosa. It is concluded that DGR, often present in severe reflux esophagitis, causes mucosal growth of the foregut of rats. This trophic response may explain why severe reflux esophagitis is associated with an increased risk of esophageal adenocarcinoma. DGR-induced growth stimulation of the foregut is potentiated by gastric acid suppression, suggesting that chronic antisecretory medication in gastroesophageal reflux may not always be advisable. Omeprazole + DGR caused severe esophageal damage, which may explain why antisecretory medication may fail to heal severe reflux esophagitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8943968&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Evidence that endogenous GRP in rat stomach mediates omeprazole-induced hypergastrinemia.

Takehara Y, Sumii K, Tari A, Yoshihara M, Sumii M, Haruma K, Kajiyama G, Wu SV, Walsh JH.

First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.

To investigate the physiological role of endogenous gastrin-releasing peptide (GRP) in regulating the release of gastrin, we evaluated the response of intragastric pH, gastrin, and GRP after omeprazole treatment in rats. A significant elevation of the plasma level of GRP (P < 0.01) and a significant reduction of the antral content of GRP (P < 0.05) were observed after the administration of 100 mg/kg omeprazole. The antral content of GRP was significantly decreased 12 h after omeprazole administration and thereafter gradually returned to control levels. Peak values for intragastric pH and plasma GRP were observed 3 h after omeprazole administration and before the peak of serum gastrin. The bombesin antagonist [D-Phe6]-bombesin-(6,13)-methyl ester significantly inhibited gastrin release after omeprazole treatment (P < 0.05). These observations indicate that omeprazole-induced inhibition of acid secretion stimulates the release of GRP and suggest that the secretion of GRP induced by omeprazole may stimulate the secretion of gastrin, at least in the early phase.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8944693&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Higher AUCs on oral administration of omeprazole and felodipine in Indian volunteers--are they clinically important?

Joseph T, Gowrishankar R.

Department of Pharmacology, St John's Medical College, Bangalore.

Bioavailability studies with single oral doses of omeprazole 20 mg (enteric coated formulation) and felodipine 10 mg (extended release formulation) were performed in Indian volunteers to confirm that adequate plasma concentrations are obtained in Indian subjects. Plasma samples were analysed by chromatographic methods. The AUCs of omeprazole were about 3 fold higher and those of felodipine 2 fold higher than AUCs reported in Western subjects. This has no toxicological implications with respect to omeprazole, but whether lower dose of omeprazole may be sufficient in Indian patients with acid related diseases would require acid inhibition studies. In the case of felodipine the higher AUCs in Indian subjects suggest a need for a lower strength formulation (2.5 mg) to fine-titrate the dosage to obtain optimal antihypertensive effects with minimal adverse effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8950143&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Helicobacter pylori eradication in clinical practice: one-week low-dose triple therapy is preferable to classical bismuth based triple therapy.

Goddard AF, Spiller RC.

Division of Gastroenterology, University Hospital, Nottingham, UK.

BACKGROUND: Both classical 2-week bismuth based triple therapy and the newer 1-week low-dose omeprazole based triple therapies achieve high Helicobacter pylori eradication rates in controlled clinical trials and are in widespread use in routine clinical practice. However, their efficacy and acceptability in this setting is unproved. METHODS: Over a 1-year period, the notes for patients attending a dedicated H. pylori treatment clinic were audited. Assessments were made of patient demographics, diagnosis, smoking habits, use of H2-antagonists, regimen used, efficacy of treatment, compliance and side-effects experienced. RESULTS: 223 sets of notes were audited. 89 patients received bismuth, tetracycline and metronidazole for two weeks and 111 patients received omeprazole, clarithromycin and either metronidazole (63 patients) or tinidazole (48 patients) for 1 week. Successful eradication was achieved in 75/89 (84.3%), 56/63 (89%) and 42/48 (88%), respectively, (P = N.S.). Severe side-effects occurred in 11 (12%) of patients receiving bismuth based treatment compared to 1 (0.9%) patient receiving omeprazole based regimens (P < 0.02). Treatment failure in patients receiving omeprazole based treatment was associated with smoking (P < 0.05). CONCLUSIONS: Outside the context of clinical trials, both regimens achieved acceptable eradication rates. However, 1-week low-dose therapy is preferable due to the lower incidence of severe side-effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8971303&dopt=Abstract omeprozole Prilosec