omeprazole, Prilosec
Prolonged effect of omeprazole on the 14C-urea breath test.

Chey WD, Spybrook M, Carpenter S, Nostrant TT, Elta GH, Scheiman JM.

Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0362, USA.

OBJECTIVES: We investigated omeprazole's effect on 14C-urea breath testing. We also determined the duration of omeprazole's effect on the breath test. Finally, we studied whether effects on breath testing were dose dependent. METHODS: Fifty-seven employees and outpatients were screened for Helicobactor infection. Those positive for serology, CLO, or histology were asked to undergo baseline breath testing. Those with a positive breath test took omeprazole 20 mg/day for 14 days followed by repeat breath testing, 1, 3, and 5 days after therapy. Subjects with persistently positive breath tests despite omeprazole 20 mg/day were asked to take omeprazole 20 mg b.i.d. for 14 days. Repeat breath tests were performed as above. RESULTS: Thirteen of 57 had HP infection. Ten of 13 underwent a baseline breath test. Eight of 10 with baseline breath test experienced a significant decrease in expired 14CO2 after omeprazole 20 mg/day. Five of 13 with active HP infection developed a negative breath test after omeprazole. All subjects had a positive breath test within 5 days of stopping omeprazole 20 mg/day. Five of eight with persistently positive breath tests despite omeprazole 20 mg/day took omeprazole 40 mg/day. Four of five developed a significant decrease in 14CO2 excretion after omeprazole. All subjects had a positive breath test within 5 days of stopping omeprazole 40 mg/day. CONCLUSIONS: Recent treatment with omeprazole 20 mg/day led to a false-negative breath tests in 38.5%. This effect appeared to be dose dependent and lasted up to 5 days after cessation of omeprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8561151&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effect of omeprazole and feeding on plasma gastrin in patients with achlorhydria.

Banerjee S, Ardill JE, Beattie AD, McColl KE.

Gastrointestinal Centre, Southern General Hospital, Glasgow, UK.

BACKGROUND: The mechanism of hypergastrinaemia during omeprazole therapy is unclear, but is generally assumed to be entirely a consequence of acid suppression. However, direct stimulation of G cells by omeprazole could also be a factor. In order to further investigate the mechanism of omeprazole-induced hypergastrinaemia, we have studied the effects of the drug on plasma gastrin in patients with achlorhydria, in whom altered acid secretion cannot play a role. METHODS: We estimated fasting and peptone meal stimulated plasma gastrin in nine patients (seven female) with pernicious anaemia and achlorhydria, before and on the final day of 4 weeks' dosing with omeprazole 40 mg daily. RESULTS: Despite the high fasting gastrin concentrations, the peptone meal produced a further elevation in plasma gastrin concentrations, median gastrin concentrations rising from 1500 ng/L (range 225-10,875 ng/L) to 3750 ng/L (range 585-15,600 ng/L) post-prandially (P = 0.004). The median post-prandial rise in plasma gastrin at this initial visit was 44% (3-260%), and the median time interval until plasma gastrin concentrations returned to fasting levels was 120 min (range 10- > 150 min). There was a significant negative correlation between fasting plasma gastrin concentrations and the percentage increase in plasma gastrin levels in response to meal stimulation (Spearman correlation coefficient -0.79, P = 0.01). Fasting plasma gastrin concentrations were similar pre-omeprazole (median 1950 ng/L, range 240-16,500 ng/L) and post-omeprazole (median 1500 ng/L, range 315-7650 ng/L). Likewise, peak plasma gastrin concentrations were also similar pre-omeprazole (median 2700 ng/L, range 585-16,500 ng/L) and post omeprazole (median 3420 ng/L, range 720-11,250 ng/L). CONCLUSIONS: (i) The hyperplastic G cell mass in patients with pernicious anaemia can be further stimulated by a peptone meal, which causes a prolonged rise in plasma gastrin concentrations. (ii) There is a negative correlation between fasting plasma gastrin concentrations and the percentage increase in plasma gastrin levels in response to meal stimulation. (iii) Omeprazole has no effect on plasma gastrin in achlorhydric patients, which is consistent with its hypergastrinaemic effect being entirely secondary to acid inhibition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8580270&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effect of omeprazole on diazepam disposition in the rat: in vitro and in vivo studies.

Zomorodi K, Houston JB.

Department of Pharmacy, University of Manchester, UK.

PURPOSE. The inhibitory effects of omeprazole on diazepam metabolism in vitro and in vivo are compared in the rat. METHODS. 3-hydroxylation and N-demethylation of diazepam was investigated in the presence of a range of omeprazole concentrations (2-500 microM) in hepatic microsomes and hepatocytes. Zero order infusions together with matched bolus doses of omeprazole were used to achieve a range of steady state plasma concentrations (10-50mg/L) and to study the diazepam-omeprazole interaction in vivo. RESULTS. The 3-hydroxlation pathway was more prone to inhibition (KIs 108 +/- 30 and 28 +/- 11 microM in microsomes and hepatocytes, respectively) than the demethylation pathway (KIs of 226 +/- 76 and 59 +/- 27 microM in microsomes and hepatocytes, respectively). In both in vitro systems, the mechanism of inhibition was competitive with Km/KI ratios larger than 1 for the 3HDZ pathway and smaller than 1 for the NDZ pathway. There was an omeprazole concentration dependent decrease in diazepam clearance in vivo which could be modelled using a simple inhibition equation with a KI of 57 microM (19.8mg/L). In contrast there was no statistically significant change in the steady state volume of distribution for diazepam in the presence of omeprazole. CONCLUSIONS. The in vivo KI for the omeprazole: diazepam inhibition interaction shows closer agreement with the KI values obtained in hepatocytes than with those observed in microsomes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8592663&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Ultrastructure of enterochromaffin-like cells in rat stomach: effects of alpha-fluoromethylhistidine-evoked histamine depletion and hypergastrinemia.

Chen D, Zhao CM, Andersson K, Sundler F, Hakanson R.

Department of Pharmacology, University of Lund, Solvegatan 10, S-22362 Lund, Sweden.

Histamine-producing enterochromaffin-like (ECL) cells are numerous in the oxyntic mucosa of the rat stomach. They respond to gastrin by secretory activation, hypertrophy and hyperplasia. They contain cytoplasmic granules (median profile diameter 120 nm), secretory vesicles (180 nm) and microvesicles (70 nm). alpha-Fluoromethylhistidine (alpha-FMH) depletes histamine from the ECL cells by inhibiting the histamine-forming enzyme histidine decarboxylase. Long-term hypergastrinemia, evoked by omeprazole, increases the ECL-cell histamine concentration. The way in which chronic histamine depletion affects omeprazole-induced ECL-cell hypertrophy, and the ways in which granules and vesicles in the ECL cells respond to alpha-FMH and/or omeprazole have been studied. Rats were treated with alpha-FMH (3 mg/kg per h subcutaneously), omeprazole (400 micromol/kg per day orally), alpha-FMH+omeprazole, or vehicle for 6 weeks. ECL cell profiles in electron micrographs were analysed panimetrically. The results show that the omeprazole-evoked hypertrophy of the ECL cells is not affected by depletion of ECL-cell histamine, thereby supporting the view that ECL-cell histamine is not important for full expression of the gastrin-evoked trophic effects on the ECL cells. The loss of ECL-cell histamine following treatment with alpha-FMH and with alpha-FMH+omeprazole is associated with a greatly reduced size of the secretory vesicle compartment. The granules, on the other hand, are unaffected by alpha-FMH and alpha-FMH+omeprazole. Omeprazole treatment leads to the appearance of numerous vacuoles (with profile diameter greater than 500 nm); such vacuoles are not observed in the ECL cells of rats treated with alpha-FMH or alpha-FMH+omeprazole. The omeprazole-induced increase in ECL-cell histamine is associated with an increase in the compartment composed of secretory vesicles and vacuoles. The findings support the hypothesis that secretory vesicles (and vacuoles) represent a major storage site of ECL-cell histamine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8593676&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Cost-effectiveness of treatment regimens for the eradication of Helicobacter pylori in duodenal ulcer.

Vakil N, Fennerty MB.

University of Wisconsin Medical School, Milwaukee, USA.

BACKGROUND: Eradication of Helicobacter pylori with antimicrobials was recommended by a recent NIH consensus panel for all infected patients with peptic ulcer disease. The precise regimen that should be used for eradication of the infection remains uncertain because of the variety of regimens described, variable results with the regimens, and difficulties in predicting drug compliance outside clinical trials. METHODS: A decision analysis tree was developed with three regimens that are widely used regimens for the eradication of H. pylori: 1) 2-wk triple drug therapy (metronidazole, bismuth, tetracycline with H2 receptor antagonist), 2) 2-wk omeprazole and amoxicillin, and 3) 2-wk omeprazole and clarithromycin. Traditional H2 receptor antagonist therapy was used for comparison. A 2-yr time period was chosen for study to allow sufficient time for relapse and to evaluate its effect on the treatment strategy. Probabilities for eradication, compliance, and metronidazole resistance were determined from published data, and assumptions were tested by sensitivity analysis. RESULTS: Standard 2-wk triple drug therapy was the least expensive strategy ($720), and conventional H2 receptor antagonist therapy was the most expensive ($1791). Costs with 2-wk therapy with omeprazole and clarithromycin ($768) were lower than with omeprazole and amoxicillin ($1028). CONCLUSIONS: Treatment to eradicate H. pylori in infected patients with duodenal ulcer is a less expensive strategy than traditional therapy with H2 receptor antagonists. Triple drug therapy is the optimal regimen in areas where metronidazole resistance rates are < 36% and compliance is > 53%. Omeprazole and amoxicillin is not cost-effective unless eradication rates are greater than 74%. Dual drug therapy with omeprazole and clarithromycin is effective in regions where metronidazole resistance is high or where it is anticipated that there would be poor compliance with the more complicated triple drug therapy regimen.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8607487&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome.

Harding SM, Richter JE, Guzzo MR, Schan CA, Alexander RW, Bradley LA.

Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Alabama, Birmingham, 35294, USA.

PURPOSE: To determine (1) the appropriate omeprazole (Prilosec) dose required for adequate acid suppression in asthmatics with gastroesophageal reflux, (2) whether aggressive acid suppressive therapy of gastroesophageal reflux improves asthma outcome in asthmatics with gastroesophageal reflux, (3) the time course of asthma improvement, and (4) demographic, esophageal, or pulmonary predictors of a positive asthma response to antireflux therapy. PATIENTS AND METHODS: Thirty nonsmoking adult asthmatics with gastroesophageal reflux (asthma defined by American Thoracic Society criteria and reflux defined by symptoms and abnormal 24-hour esophageal pH testing) were recruited from the outpatient clinics of a 900-bed university hospital. Patients underwent baseline studies including a demographic questionnaire, esophageal manometry, dual-probe 24-hour esophageal pH test, barium esophogram, and pulmonary spirometry. During the 4-week pretherapy phase, patients recorded reflux and asthma symptom scores and peak expiratory flow rates (PEFs) upon awakening, 1 hour after dinner, and at bedtime. Patients began 20 mg/d omeprazole, and the dose was titrated until acid suppression was documented by 24-hour pH test. Patients remained on this acid suppressive dose for 3 months. Responders were identified by a priori definitions: asthma symptom reduction by >20% and/or PEF increase by >20%. Asthma symptom scores, PEF's baseline and posttherapy pulmonary spirometry were analyzed. RESULTS: Twenty-two (73%) patients were asthma symptom and /or PEF responders: 20 (67%) were asthma symptom responders, and 6 (20%) were PEF responders. Responders reduced their asthma symptoms by 57% (P<0.001), improved their morning and night PEFs by 8% and 9% (both P <0.005), and had improvement in forced expiratory volume at 1 second (P <0.02), mean forced expiratory flow during the middle half (25% to 75%) of the forced vital capacity (P <0.04), and peak expiratory flow (P <0.01) with acid suppressive therapy. Mean acid suppressive dose of omeprazole was 27 mg/d (+/-2.2) with 27% (8) patients requiring more than 20 mg/d. The presence of regurgitation or excessive proximal esophageal reflux predicted asthma response with 100% sensitivity, 100% negative predictive value, specificity of 44% and a positive predictive value of 79%. CONCLUSIONS: Acid suppressive therapy with omeprazole improves asthma symptoms and/or PEFs by >20% and improves pulmonary function in 73% of asthmatics with gastroesophageal reflux after 3 months of acid suppressive therapy. Many asthmatics (27%) required >20 mg/d of omeprazole to suppress acid. The presence of regurgitation and/or excessive proximal esophageal reflux predicts a positive asthma outcome.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8610725&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Folate synthesized by bacteria in the human upper small intestine is assimilated by the host.

Camilo E, Zimmerman J, Mason JB, Golner B, Russell R, Selhub J, Rosenberg IH.

University Hospital de Santa Maria, Servico de Medicina 2, Lisbon, Portugal.

BACKGROUND & AIMS: Some intestinal flora are known to synthesize folate. The aim of this study was to determine whether folate synthesized by small intestinal flora is assimilated by the human host. METHODS: Subjects with atrophic gastritis and healthy volunteers were studied before and after omeprazole administration. A double-lumen perfusion tube was placed in the duodenum. 3H-labeled P-aminobenzoic acid, a precursor substrate for bacterial folate synthesis, was perfused. Downstream intestinal aspirates and a 48-hour urine collection were obtained. RESULTS: Atrophic gastritis and omeprazole administration were associated with increases in duodenal pH and in small intestinal flora. Bacterially synthesized folates were isolated from the intestinal aspirates. Tritiated 5-methyltetrahydrofolate, a major metabolite of folate, was isolated from the urine of omeprazole-treated subjects in greater quantities than from drug-free subjects (P<0.01); the quantity of tritiated 5-methyltetrahydrofolate in the urine of the subjects with atrophic gastritis was similarly elevated. CONCLUSIONS: (1) Mild bacterial overgrowth caused by atrophic gastritis and administration of omeprazole are associated with de novo folate synthesis in the lumen of the small intestine; (2) the human host absorbs and uses some of these folates; and (3) the contribution to folate nutriture from this source remains unclear.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8613033&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Reversible inhibition of rat gastric H+/K+-ATPase by T-330, 2-[2-dimethylaminobenzyl)sulfinyl]-1-(3-methylpyridine-2-yl)imidazole.

Kinoshita M, Saito N, Noto T, Tamaki H.

Department of Pharmacology, Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.

The effect of 2-[(2-dimethylaminobenzyl)sulfinyl]-1-(3-methylpyridine-2-yl)imidazole (T-330), on rat gastric H+/K+-ATPase was studied in vitro and in vivo in comparison with the irreversible proton pump inhibitor omeprazole. T-330 and omeprazole inhibited rat gastric H+/K+-ATPase at pH 6.1, and their IC50 values were 75 microM and 4.6 microM, respectively. Recovery from the T-330-inhibited H+K/+-AtPase activity was effected by beta-mercaptoethanol at concentrations above 10 microM, whereas significant recovery from the inhibition by omeprazole required 100 mM. When intraduodenally administered, T-330 (0.6-10 mg/kg) induced a more potent yet shorter-lasting inhibition of both gastric H+/K+ -ATPase activity and gastric acid secretion than did omeprazole (2.5-40 mg/kg). Recovery of the gastric H+/K+-ATPase activity depressed by omeprazole was completely blocked by an inhibitor of protein synthesis, cycloheximide, whereas that by T-330 was not prevented. This indicates that restoration of the enzyme activity after inhibition in vivo by T-330 does not require de novo synthesis of the enzyme in contrast to inhibition by omeprazole. beta-Mercaptoethanol (1 mM) fully restored the H+/K+-ATPase activity inhibited in vivo by T-330 but not by omeprazole. These observations indicate that T-330 reversibly inhibits gastric H+/K+-ATPase, resulting in a short-lasting antisecretory effect, and that the sulfhydryl groups of the enzyme are involved in the action of T-330.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8613931&dopt=Abstract omeprozole Prilosec