omeprazole, Prilosec
The effects of omeprazole and famotidine on mucin and PGE2 release in the rat stomach.

Yoshimura K, Delbarre SG, Kraus E, Boland CR.

Department of Internal Medicine, VA Medical Centre and the University of Michigan School of Medicine Ann Arbor, MI, 92093-0688, USA.

BACKGROUND: Gastric antisecretory agents may inhibit the synthesis or secretion of gastric mucin during acid suppression, which would interfere with mucosal protection and limit the efficacy of the agents. METHODS: Rats were dosed with famotidine, omeprazole, or buffer control for 4 weeks. Mucin synthesis, mucin histochemistry, mucin carbohydrate composition and prostaglandin E2 (PGE2) release were measured during and after drug treatment. RESULTS: PGE2 release was maximally inhibited after 2 weeks of omeprazole or 4 weeks of famotidine. Total glycoprotein synthesis was inhibited at all times by omeprazole, but only after the cessation of dosing with famotidine. Sulphated glycoprotein synthesis was inhibited by both drugs at 2 weeks. PGE2 release and sulphated glycoprotein synthesis were restored to control values or more by the 5th day after the end of dosing, at which time total glycoprotein synthesis was significantly suppressed in both groups. Histologically, a reduction of PAS-positive surface mucus was observed after 2 weeks of dosing in both groups. Both famotidine and omeprazole reduced the sialic acid content during and after treatment. CONCLUSIONS: These results suggest that long-term anti-secretory therapy also affects the production of factors involved in primary gastric mucosal defence, which should be considered in the assessment of response to treatment in clinical trials.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8871451&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Pharmacokinetic evaluation of omeprazole suspension following oral administration in rats: effect of neutralization of gastric acid.

Watanabe K, Matsuka N, Furuno K, Eto K, Kawasaki H, Gomita Y.

Department of Hospital Pharmacy, Okayama University Medical School, Japan.

In order to evaluate a clinical use of omeprazole suspension, we examined the pharmacokinetics of omeprazole after oral administration in rats. Although the administration of omeprazole suspension buffered by NaHCO3 solution did not produce a significant increase in the area under the concentration-time curve (AUC) value compared with non-buffered group, the administration of NaHCO3 buffer immediately after dosing of omeprazole suspension buffered by NaHCO3 caused a significant increase in the AUC value. These results suggest that the NaHCO3 treatment following the administration of omeprazole buffered suspension effectively decreased the degradation of the compound by gastric acid. Therefore, the successive administration of NaHCO3 solution after the omeprazole dosing seems to be a simple and useful method for the administration to patients who cannot receive tablets.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8874584&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Mechanism of inhibition of H+, K(+)-ATPase by sodium 2-[[4-(3- methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl]-1H-benzimidazole (E3810).

Nochi S, Yokoyama Y, Narukawa M, Ebine K, Murahashi M, Kawakami Y, Asakawa N, Sato T.

Tsukuba Research Laboratories, Eisai Co., Ltd., Japan.

Sodium 2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl ]- 1H-benzimidazole (E3810) and omeprazole inhibit gastric acid secretion through inhibition of the activity of H+, K(+)-ATPase present in parietal cell membrane vesicles, by chemical modification of SH groups in the enzyme molecule. In order to clarify the mechanism of the chemical modification, reaction products of E3810 and omeprazole with 2-mercaptoethanol under acidic conditions (pH 3, 4, 5, 6) were isolated by HPLC, and subjected to structural analysis by UV, 1H-NMR and mass spectrometry. E3810 and omeprazole appeared to undergo two kinds of reactions, affording disulfide-type products (type I reaction) and sulfide-type products (type II reaction). The rates of these reactions were determined by HPLC, and the stability of the products in the presence and absence of glutathione was investigated. In the case of E3810, type I reaction was found to proceed faster than type II reaction at every pH value studied. The type I reaction of E3810 was faster than that of omeprazole. The rate of type I reaction decreased at pH 5 and 6, especially for omeprazole, and the contribution of type II reaction increased as the pH of the reaction mixture was increased. The sulfide-type modification products were stable, whereas the formation of the disulfide-type modification products was reversed by the action of endogenous SH compounds such as glutathione. These results suggest that higher inhibitory activity of E3810 against gastric acid secretion and faster recovery of the enzyme activity after inhibition by E3810 can be expected, as compared with those of omeprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8882453&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Omeprazole versus histamine H2 receptor antagonists in the treatment of acute upper non-variceal bleeding.

Mohamed SA, al Karawi MA.

Department of Gastroenterology, Armed Forces Hospital, Riyadh, Saudi Arabia.

BACKGROUND/AIMS: To compare the efficacy of omeprazole, a proton pump inhibitor, with Histamine H2 receptors antagonists in the control and recurrence of non-variceal upper gastrointestinal bleeding. PATIENTS AND METHODS: Seventy-one patients (Group A, Omeprazole) with definite diagnosis of upper gastrointestinal bleeding of non-variceal origin during January 1993-Dec.1994, compared retrospectively with 119 patients (Group B, Ranitidine) with similar criteria during 1987-1993. Patients in both groups were matched as compared to sex, age and risk factors. Active treatment was omeprazole 40 mg B.D (twice daily) and then orally in group A compared with ranitidine intravenously 50mg TDS (three times daily) and then 150 mg B.D orally in group B. All patients in both groups had endoscopy at the time of presentation or within 24 hours. Endoscopic treatment was applied in some of the patients to arrest acute bleeding. The efficacy of treatment was gauged by the number of blood transfusions needed to maintain Hb., evidence of re-bleeding and need for surgery. RESULTS: The patients were well matched for endoscopic diagnosis except duodenal ulcers, which were more common in group A (P < 0.05). In group A out of 71 patients, 5 had rebleeding and 2 required surgery. In group B, out of 119 patients 12 rebled and 10 required surgery. Statistically there was no difference between groups (p = 0.52 by using Kendall's Tau B). Nine patients in omeprazole group received 2 units blood transfusion, 6 patients > 4 units and 3 patients > 6 units, while in the H2 blocker group, 16 patients received 2 units, 15 patients received > 4 units, and 3 patients > 6 units of blood transfusion. Statistically there was no difference between groups with regard to number of transfusions, rebleed or the need for surgery. CONCLUSIONS: In our study we found no difference between omeprazole and histamine H2 receptors antagonists in controlling and recurrence of upper gastrointestinal bleeding.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8884305&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Omeprazole produces parietal cell hypertrophy and hyperplasia in humans.

Driman DK, Wright C, Tougas G, Riddell RH.

Department of Pathology, McMaster University Medical Centre, Hamilton, Ontario, Canada.

While there is evidence that omeprazole may induce changes in parietal cells, the effect of acid suppression on parietal cells in humans is poorly documented. This study was undertaken to evaluate the effects of omeprazole in human parietal cells over time. The light microscopic morphology of parietal cells in gastric biopsies from 17 patients on omeprazole were compared with those from 13 patients on ranitidine and 20 patients on no acid-lowering medication. Light microscopic and ultrastructural morphology of parietal cells was also evaluated in an additional 14 patients before and after omeprazole administration. Objective measurements of parietal cell height, mass and number were analyzed using analyses of variance. Electron microscopy was used to evaluate parietal cell enlargement. Twenty-five of 31 biopsies from patients on omeprazole, 1 of 13 from patients on ranitidine, and 0 of 20 from patients on neither drug showed parietal cell enlargement. Parietal cell height, mass, and number were increased in omeprazole-treated patients compared with ranitidine-treated patients and those on neither drug, and with the group also evaluated prior to beginning omeprazole treatment. Parietal cell height and mass were increased in patients on omeprazole longer than 12 months compared with biopsies from patients on the drug for less than 12 months. Resin-embedded sections and electron microscopy showed enlarged parietal cells with prominence of cytoplasmic tubulovesicles with sparse secretory canaliculi. Parietal cell hypertrophy and hyperplasia develops in patients on chronic omeprazole therapy; this can be recognized on routine examination of histologic sections. These morphologic changes increase with duration of therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8888719&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effect of nizatidine 300 mg at night and omeprazole 20 mg in the morning on 24-hour intragastric pH and bacterial overgrowth in patients with acute duodenal ulcer.

Brummer RJ, Stockbrugger RW.

Department of Gastroenterology, University Hospital Maastricht, The Netherlands.

The study investigated the effect of either nocturnal acid suppression by the H2 antagonist nizatidine 300 mg at night or prolonged acid suppression by the proton- pump inhibitor omeprazole 20 mg in the morning, during four weeks, on intragastric pH profile, occurrence of bacterial growth in gastric fluid and biopsies, and healing rate in 23 patients with an acute duodenal ulcer. The endoscopic healing rate did not differ significantly between the two treatment modalities. The 24-hr acid secretion was significantly more reduced by omeprazole than nizatidine (P < 0.002). After treatment by nizatidine and omeprazole, respectively, median 24-hr intragastric pH increased from 1.5 to 1.8 (P < 0.01) and from 1.5 to 6.1 (P < 0.01), respectively. Nighttime acid inhibition did not differ significantly. The difference in gastric bacterial colonization after either omeprazole or nizatidine did not reach significance. However, median 24-hr pH and the fraction of the day with pH < 3 and pH < 4 were significantly correlated to bacterial colonization of the gastric fluid (P < 0.05).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8888720&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Omeprazole attenuates oxygen-derived free radical production from human neutrophils.

Suzuki M, Mori M, Miura S, Suematsu M, Fukumura D, Kimura H, Ishii H.

Department of Internal Medicine and Biochemistry, School of Medicine, Keio University, Tokyo, Japan.

Neutrophil-derived oxygen radicals have been implicated in the pathogenesis of gastrointestinal disorders such as acute gastric mucosal injury induced by ischemia-reperfusion or by nonsteroidal antiinflammatory drugs (NSAIDs). The objectives of the present in vitro and clinical study were to determine whether omeprazole inhibits the production of toxic oxidants from neutrophils and to evaluate whether this drug affects intralysosomal pH. The respiratory burst of human neutrophils were was measured by luminol-dependent chemiluminescence (ChL) assay. The lysosomal pH of neutrophil was assessed by the fluorescence intensity ratio of phagocytized FITC-dextran using a digital-fluorescence video microscope. In vitro studies revealed that omeprazole (1-100 microM) dose dependently inhibited the ChL value of purified neutrophils that were elicited by FMLP (f-methionyl-leucyl-phenylalanine) or opsonized zymosan. Lysosomal pH was also increased in a dose-dependent manner by pretreatment with omeprazole. Healthy volunteers administered omeprazole, 40 mg/d for 7 d, showed a significant reduction in ChL values in peripheral neutrophils. These results suggest that omeprazole can inhibit the production of toxic oxidants by activated neutrophils. The action of omeprazole may be associated with a malfunction of lysosomal oxidant-producing enzymes due to an elevated intralysosomal pH.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8891677&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
The effect of changes in gastric pH induced by omeprazole on the absorption and respiratory depression of methadone.

de Castro J, Aguirre C, Rodriguez-Sasiain JM, Gomez E, Garrido MJ, Calvo R.

Pharmacology Department, Basque Country University School of Medicine, Leioa, Spain.

The effect of omeprazole (2 mg kg-1 i.v.) on respiratory depression induced in rats by acute oral methadone administration (5 mg kg-1) was examined and compared with control animals that only received methadone. Quantitative assessments of arterial Pco2,Po2, pH, and respiratory rate were employed as criteria for evaluation. Intragastric pH was measured in each rat immediately before and 2 h after methadone. Plasma concentration of methadone was measured for 3 h. The relationship between drug effect and the systemic bioavailability of methadone, measured as the area under the plasma concentration-time curve (AUC0-180), was also evaluated. The intensity of the methadone-induced respiratory depression was significantly greater in the omeprazole group than in control rats. A significant variation (p < 0.01) in all respiratory parameters was detected from 30 to 120 min after methadone. Omeprazole caused a significant increase in methadone levels (Cmax = 156 +/- 6.5 ng mL-1 against 51 +/- 5.8 ng mL-1 in control; p < 0.05). AUC0-180 was higher (p < 0.05) after omeprazole treatment (18.6 +/- 1.4 micrograms mL-1 min) than in control (6.8 +/- 0.6 microgram mL-1 min). Two hours after treatment with omeprazole, intragastric pH values were significantly elevated (4.7 +/- 0.1 against 2.2 +/- 0.04) and continued increasing, being 6.4 +/- 0.1 at the end of the experiment. Correlation was observed between intragastric pH and the area under the effect- (respiratory depression-) time curve (r = 0.74; p < 0.001). A relationship between plasma methadone levels at 120 min and gastric pH (r = 0.92; p < 0.001) was detected. A significant correlation between the area under the effect-time curve (0-120 min) and AUC0-180 has been also observed (r = 0.90; p < 0.01). These pharmacokinetic and pharmacodynamic changes could be gastric pH dependent because they were mimicked when gastric pH was experimentally modified by bicarbonate whereas opposite results were obtained with acidic pH2 solution.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8894114&dopt=Abstract omeprozole Prilosec