omeprazole, Prilosec
Evaluation of omeprazole as a cost-effective diagnostic test for gastro-oesophageal reflux disease.

Bate CM, Riley SA, Chapman RW, Durnin AT, Taylor MD.

Royal Albert Edward Infirmary, Wigan, Lancashire, UK.

BACKGROUND: There is a need for a simple, therapeutic test that is of diagnostic value and can also provide rapid symptom relief in patients who present with classic, mild symptoms suggestive of gastro-oesophageal reflux disease (GERD), when the diagnosis is based on symptom assessment alone. AIM: To assess the diagnostic value of a therapeutic trial of omeprazole 40 mg in a dyspeptic population. METHODS: A total of 90 patients with symptoms suggestive of GERD entered the study. Patients underwent endoscopy and ambulatory oesophageal pH monitoring for 18-24 h. Patients then received omeprazole 40 mg o.m. for 2 weeks. RESULTS: There was a significant correlation between the diagnoses obtained from a trial of omeprazole and the diagnoses obtained from pH monitoring (P < 0. 05). There was no significant correlation between the diagnoses obtained from endoscopy and those obtained from pH monitoring. Both omeprazole and endoscopy were compared to pH monitoring as the 'gold standard' for the diagnosis of GERD and the cost per correct diagnosis with omeprazole was pound47 (95% CI: pound40- pound59) compared to pound480 (95% CI: pound396- pound608) with endoscopy. There was a complete absence of acid-related symptoms in the majority (59%) of patients after 3 days of omeprazole 40 mg therapy and, after 2 weeks, 82% of patients had experienced an improvement in overall symptoms ( 1 grade). CONCLUSIONS: We conclude that omeprazole can be used as a clinically effective tool in the initial management of GERD and that it is of diagnostic value in patients who present with typical symptoms, such as heartburn, when the diagnosis is based on symptom assessment alone.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9892880&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Simultaneous determination of omeprazole and 5'-hydroxyomeprazole in human plasma by liquid chromatography-tandem mass spectrometry.

Woolf EJ, Matuszewski BK.

Merck Research Laboratories, Department of Drug Metabolism, West Point, PA 19486, USA. woolf merck.com

A method for the simultaneous determination of omeprazole and 5'-hydroxyomeprazole in human plasma is described. Isolation of the analytes from plasma was achieved via solid-phase extraction using a polymeric sorbent based cartridge. The analytes were chromatographed under reversed-phase conditions on a Zorbax XDB-C8 column (50 x 4.6 mm). The HPLC mobile phase consisted of a mixture of acetonitrile-water (21:79, v/v) containing 10 mM ammonium hydroxide. The apparent pH of the mobile phase was adjusted to 8.5 with formic acid prior to use. A Sciex API III+ tandem mass spectrometer equipped with a heated nebulizer atmospheric pressure chemical ionization interface was used as a detector and was operated in the positive ion mode. Multiple reaction monitoring using the precursor-->product ion combinations of m/z 362-->214, 346-->198 and 316-->147 was used to detect 5'-hydroxyomeprazole, omeprazole and internal standard, respectively. The method was validated in the concentration range of 10-500 ng/ml plasma with adequate assay precision and accuracy. The assay was used to determine the cytochrome P450 2C19 phenotype of subjects participating in clinical trials of compounds under development.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9916309&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Rebound hypersecretion after omeprazole and its relation to on-treatment acid suppression and Helicobacter pylori status.

Gillen D, Wirz AA, Ardill JE, McColl KE.

University Department of Medicine & Therapeutics, Western Infirmary, Glasgow, Scotland.

BACKGROUND & AIMS: There have been conflicting reports regarding acid secretion after treatment with omeprazole. This study examined acid secretion after treatment with omeprazole and its relation to Helicobacter pylori status and on-treatment gastric function. METHODS: Twelve H. pylori-negative and 9 H. pylori-positive subjects were examined before, on, and at day 15 after an 8-week course of 40 mg/day omeprazole. On each occasion, plasma gastrin, intragastric pH, and acid output were measured basally and in response to increasing doses of gastrin 17. RESULTS: In the H. pylori-negative subjects at day 15 after omeprazole treatment, basal acid output was 82% higher (P < 0.007) and maximal acid output 28% higher (P < 0.003) than before omeprazole. The degree of increase in maximal acid output was related to both on-treatment pH and on-treatment fasting gastrin levels, being 48.0% in subjects with an on-treatment pH of >4 vs. 21. 0% in those with a pH of <4 (P < 0.02) and 49.2% in subjects with an on-treatment gastrin of >25 ng. L-1 vs. 19.8% in those with a fasting gastrin of <25 ng. L-1 (P < 0.006). At day 15 after omeprazole treatment, the H. pylori-positive subjects showed a heterogeneous response with some having increased acid output and others persisting suppression. CONCLUSIONS: Rebound acid hypersecretion occurs in H. pylori-negative subjects after omeprazole treatment. Its severity is related to the degree of elevation of pH on treatment. Persisting suppression of acid secretion masks the phenomenon in H. pylori-positive subjects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9922302&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effect of omeprazole, lansoprazole, and ranitidine on the DNA synthesis of mononuclear cells.

Peddicord TE, Olsen KM, Collier DS.

Department of Pharmacy Practice, University of Nebraska Medical Center, Omaha 68198-6045, USA.

OBJECTIVE: To examine and compare the effects of omeprazole, lansoprazole, and ranitidine on the DNA synthesis of peripheral blood mononuclear cells. DESIGN: Ex vivo laboratory study. SETTING: Clinical research laboratory of an academic medical center. SUBJECTS: Healthy volunteers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Venous blood was collected from normal subjects and peripheral blood mononuclear cells (PBMCs) were isolated using centrifugation techniques over a Ficoll-Hypaque density gradient. PBMCs were added to 12-well culture plates in four groups of media: a) control; b) control plus lansoprazole (25 microg/mL); c) control plus omeprazole (0.35 microg/mL); and d) control plus ranitidine (50 microg/mL). PBMCs were exposed to the drug for 96 hrs, with addition of phytohemagglutinin (2.5 microg/ mL) for the last 48 hrs, and 3H-thymidine (1 microCi) during the final 6 hrs. PBMCs were filtered onto glass-fiber filter paper and the radioactivity was determined by scintillation counting. Since radioactivity is measured only in those cells undergoing DNA synthesis or cell division, results are expressed as quantification of 3H-thymidine uptake. Median disintegrations per min (DPM)/number of PBMCs per well+/-SEM are reported: control 68.3+/-37.8; ranitidine 38.4 +/-94.2; lansoprazole 14.6+/-84.4; and omeprazole 15.1+/-48.9. There was a significant difference between lansoprazole vs. ranitidine (p< .01), and omeprazole vs. ranitidine (p< .05), and no significant difference between lansoprazole and omeprazole. CONCLUSIONS: This is the first study to compare the potential immunomodulating effects of these commonly used agents. Ranitidine caused increased DNA synthesis in PBMCs when compared with lansoprazole and omeprazole. This phenomenon may be an important, often disregarded, effect of histamine-2-receptor antagonists when used in postsurgical or trauma patients who have T-lymphocyte-mediated immune suppression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9934899&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Enantiomeric determination of the plasma levels of omeprazole by direct plasma injection using high-performance liquid chromatography with achiral-chiral column-switching.

Cass QB, Lima VV, Oliveira RV, Cassiano NM, Degani AL, Pedrazzoli J.

Departamento de Quimica, Universidade Federal de Sao Carlos, Sao Carlos13565-905, SP, Brazil. quezia dq.ufscar.br

A direct injection high-performance liquid chromatographic (HPLC) method, with column-switching, for the determination of omeprazole enantiomers in human plasma is described. A restricted access media (RAM) of bovine serum albumin (BSA) octyl column has been used in the first dimension for separation of the analyte from the biological matrix. The omeprazole enantiomers were eluted from the RAM column onto an amylose tris(3,5-dimethylphenylcarbamate) chiral column by the use of a column-switching valve and the enantioseparation was performed using acetonitrile-water (60:40 v/v) as eluent. The analytes were detected by their UV absorbance at 302 nm. The validated method was applied to the analysis of the plasma samples obtained from 10 Brazilian volunteers who received a 40 mg oral dose of racemic omeprazole and was able to quantify the enantiomers of omeprazole in the clinical samples analyzed. The assay was able to determine the cytochrome P450 2C19 phenotype of the subjects participating in this study.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14643507&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Choice of long-term strategy for the management of patients with severe esophagitis: a cost-utility analysis.

Heudebert GR, Marks R, Wilcox CM, Centor RM.

Department of Medicine, Birmingham Veterans Administration Medical Center, and University of Alabama at Birmingham, 35294-3296, USA. gheudebert gim.dom.uab.edu

BACKGROUND & AIMS: Omeprazole has shown remarkable efficacy and safety in the treatment of patients with gastroesophageal reflux disease (GERD); similarly, laparoscopic techniques have allowed less morbidity in patients undergoing fundoplication procedures. Concerns about the long-term cost and safety of both strategies have prompted a debate of their role in long-term management of patients with severe erosive esophagitis. METHODS: A cost-utility analysis was performed to compare two strategies: laparoscopic Nissen fundoplication (LNF) vs. omeprazole. A two-stage Markov model was used to obtain cost and efficacy estimates; all estimates were discounted at 3% per year. The time horizon was 5 years. Sensitivity analyses were performed on all relevant variables. RESULTS: Both strategies were similarly effective (4.33 quality-adjusted life years per patient), with omeprazole less expensive than LNF ($6053 vs. $9482 per patient). At 10 years, LNF and omeprazole costs were similar. Efficacy estimates were extremely sensitive to changes in quality of life associated with postoperative symptoms and long-term use of medication. CONCLUSIONS: Medical therapy is the preferred treatment strategy for most patients with severe erosive esophagitis. Individuals with a long life expectancy are good candidates for LNF if postoperative morbidity is low and GERD symptoms remain abated for many years.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9097989&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Omeprazole induces high intraglandular pressure in the rat gastric mucosa.

Synnerstad I, Holm L.

Department of Physiology and Medical Biophysics, Uppsala University, Sweden.

BACKGROUND & AIMS: In a few patients receiving high doses of omeprazole for a prolonged period, cystic changes have developed in the gastric mucosa, possibly consisting of enlarged gland lumina. To investigate this question, the luminal pressure in gastric glands was studied after omeprazole treatment in Inactin-anesthetized rats. METHODS: The gland luminal pressure and mucus thickness were measured with microelectrodes. For pressure measurements (servo-null technique) the microelectrode was inserted into a gland at an angle of approximately 30 degrees to the mucosal surface. RESULTS: Animals given omeprazole by gavage, 400 micromol/kg daily for 1 week, showed high gland luminal pressures (27.4 +/- 2.4 mm Hg). Similar values were found in animals given an intravenous omeprazole injection (40 micromol/kg). Much lower pressures were noted after vehicle or pentagastrin infusion. The thickness of the lower, firm mucus layer was not altered by omeprazole treatment. CONCLUSIONS: The significantly higher gland luminal pressure after treatment with omeprazole, compared with the values during pentagastrin or vehicle infusion, cannot be explained by increased mucus thickness. The results suggest accumulation of fluid in the gland lumen caused by increased resistance to outflow from the gland. This might explain the proposed enlargement of gland lumina.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9098006&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Evidence that rat stomach ECL cells represent the main source of circulating pancreastatin.

Kimura K, Chen D, Lindstrom E, Zhao CM, Hakanson R.

Departament of Pharmacology, University of Lund, Sweden.

Recently, we showed that the ECL cells in the oxyntic mucosa of the rat stomach are an important source of circulating pancreastatin, a fragment of chromogranin A. The present study examined how much the ECL cells contribute to the circulating levels of pancreastatin during omeprazole-evoked hypergastrinemia. Rats received omeprazole (400 mumol kg-1 day-1) by the oral route for 3 weeks. Two weeks after the start of the treatment, the rats were subjected to a sham operation or fundectomy. The concentrations of gastrin and pancreastatin in serum were monitored before and after the operations. The ECL cells were visualized by pancreastatin immunostaining and their number was determined. The activity of oxyntic mucosal histidine decarboxylase (HDC) was measured before and after 2 weeks of omeprazole treatment. Omeprazole-induced hypergastrinemia resulted in elevated serum pancreastatin and increased oxyntic mucosal HDC activity. Pancreastatin-immunoreactive cells were equally numerous before and after 2 weeks of omeprazole treatment. After surgical removal of the ECL cells by fundectomy, the serum gastrin concentration remained high whereas the serum pancreastatin concentration decreased by 90%. We conclude that the ECL cells in omeprazole-treated rats are responsible for 90% of circulating pancreastatin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9100284&dopt=Abstract omeprozole Prilosec