omeprazole, Prilosec
Lack of effect of omeprazole in oral acenocoumarol anticoagulant therapy.

Vreeburg EM, De Vlaam-Schluter GM, Trienekens PH, Snel P, Tytgat GN.

Dept. of Gastroenterology and Hepatology, Slotervaart Hospital, Amsterdam, The Netherlands.

BACKGROUND: Omeprazole is eliminated almost completely by hepatic metabolism within the cytochrome P-450 system and might inhibit the oxidative metabolism of other drugs. This is particularly relevant for compounds with a narrow therapeutic range, such as acenocoumarol. In this study we evaluated the effect of omeprazole use in patients receiving continuous acenocoumarol therapy. METHODS: One thousand and fifty-seven patients receiving long-term oral acenocoumarol combined with omeprazole were selected retrospectively. In 118 of these patients omeprazole was considered the only factor of possible influence on anticoagulant therapy. The control group consisted of 299 age- and sex-matched patients taking acenocoumarol without interfering medication. Dose adjustment of acenocoumarol on starting omeprazole therapy was indicated by clinically relevant changes in coagulation time. RESULTS: No adaptation of the anticoagulant dose was necessary in 74 of 118 omeprazole patients (62.7%), compared with 169 of 299 controls (56.5%). A higher dose was necessary in 30 of 118 omeprazole patients (25.4%), compared with 84 of 299 controls (28.0%). In 14 of 118 omeprazole patients (11.9%) a lowering of the anticoagulant dose was required, compared with 46 of 299 controls (15.4%). CONCLUSIONS: We found no evidence of any interaction between omeprazole and acenocoumarol. It seems likely that omeprazole can be administered safely to patients treated with acenocoumarol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9361171&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Fundic gland polyps developing during omeprazole therapy.

el-Zimaity HM, Jackson FW, Graham DY.

Baylor College of Medicine, VAMC, Houston, Texas, USA.

OBJECTIVE: Side effects of omeprazole therapy include reversible hypergastrinemia, entero chromaffin-like hyperplasia, and possibly acceleration of atrophic gastritis in the gastric corpus in patients with Helicobacter pylori infection. The objective of this report is to describe six cases of fundic gland polyps that developed while omeprazole was being used for Barrett's esophagus. METHODS: Three women and three men developed fundic gland polyps after 1-5 yr of omeprazole therapy, 20 mg/day. In the index case, fundal polyps developed after 2 yr of continuous omeprazole therapy. Omeprazole was stopped, but because of poor clinical efficacy with H2-blockers, it was reinstated. RESULTS: After 4 yr of therapy, multiple large fundal polyps were present. Histology of all lesions revealed characteristic fundal gland polyps with multiple cystic dilations. None of the patients had H. pylori infection. Serum gastrin was normal in four and slightly increased in two. CONCLUSION: These cases support the possible causal relation between the use of omeprazole and the development of fundic gland polyps in patients without H. pylori gastritis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9382052&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Erosive duodenitis: prevalence of Helicobacter pylori infection and response to eradication therapy with omeprazole plus two antibiotics.

Gisbert JP, Boixeda D, de Argila CM, Bermejo F, Redondo C, de Rafael L.

Service of Gastroenterology, Ramon y Cajal Hospital, Department of Medicine, Alcala de Henares University, Madrid, Spain.

OBJECTIVES: To study the prevalence of Helicobacter pylori infection in patients with erosive duodenitis (ED), the associated gastric histological lesions and their response to eradication therapy with omeprazole plus two antibiotics. METHODS: A prospective study was made of 57 patients with ED (mean age 46 +/- 16 years, 72% males). At endoscopy, biopsies from gastric antrum and body were obtained for histological study (haematoxylin and eosin). A 13C-urea breath test was also performed. Omeprazole 20 mg twice daily plus two antibiotics (amoxycillin 1 g twice daily, clarithromycin 500 mg twice daily, metronidazole 500 mg twice daily) were administered for 1 week. Endoscopy and breath test were repeated 1 month after completing therapy, and the breath test was performed again at 6 months. RESULTS: All patients were H. pylori positive. Overall eradication was achieved in 86% (95% CI 75-93%). Duodenal erosion healing was obtained in 45 patients (79%). Healing was achieved in 86% (CI 73-93%) of cases with successful eradication therapy, but only in 3/8 (37%; CI 8.5-75%) patients with therapy failure (P < 0.01). In the multivariate analysis, H. pylori eradication was the only variable which correlated with erosion healing (odds ratio 10; CI 2-51; P < 0.01). Histological improvement, in both the gastric antrum and body, was demonstrated when eradication was achieved (P < 0.001). Six months after diagnosis H. pylori absence was confirmed in all patients with initial therapy success (all of them asymptomatic), and infection was confirmed in the eight patients who were H. pylori positive after therapy (six of them symptomatic). At 6-month follow-up, endoscopy was normal in 6/7 H. pylori-negative patients with previously persistent ED, while erosions were still present in 4/5 H. pylori-positive patients with previously persistent ED. CONCLUSION: A high prevalence (100%) of H. pylori infection in patients with ED was observed. A 1-week twice daily therapy with omeprazole plus two antibiotics (clarithromycin plus amoxycillin or metronidazole) was very effective in H. pylori eradication, duodenal erosion healing, symptomatic improvement, and in disappearance of associated histological gastritis. These observations suggest that ED should be considered a variant form of duodenal ulcer disease and treated accordingly; that is, with H. pylori eradication therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9391784&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Reversibility of omeprazole-evoked changes in the ultrastructure of ECL cells in the rat stomach.

Zhao C, Chen D, Kimura K, Hakanson R.

Department of Pharmacology, University of Lund, Solvegatan 10, S-223 62 LUND, Sweden.

The ECL cells are histamine- and peptide hormone-producing endocrine cells in the rat oxyntic mucosa. They are rich in secretory vesicles and also contain microvesicles and electron-dense granules. They operate under the control of circulating gastrin. In the present study, we examined the ECL-cell ultrastructure after long term treatment with omeprazole, which is known to induce hypergastrinemia, and after withdrawal of the drug. Rats received omeprazole (400 micromol/kg per day, orally) for 16 days and were killed 1, 5, 20, or 40 days after the last dose of the drug. Oxyntic mucosal specimens were processed for electron microscopy. Electron micrographs of ECL-cell profiles were analyzed planimetrically. The ECL-cell profile area increased promptly in response to omeprazole, the secretory vesicles and granules were reduced in number and volume density, the microvesicles were unchanged in number but reduced in volume density, and vacuoles appeared. Within a week after stopping the omeprazole treatment, the numbers and volume densities of secretory vesicles and microvesicles returned to pre-stimulation values. Also, the vacuoles disappeared promptly. The ECL-cell profile area decreased below the pre-stimulation level within five days after stopping treatment, while, in contrast, the granules increased in number and volume density. Somewhat surprisingly, the cell size and the granule compartment did not return to normal until 40 days after stopping treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9394046&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Empiric trial of high-dose omeprazole in patients with posterior laryngitis: a prospective study.

Wo JM, Grist WJ, Gussack G, Delgaudio JM, Waring JP.

Department of Internal Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

The optimal management of patients suspected with gastroesophageal reflux-related posterior laryngitis is unclear. History, physical examination, and ambulatory pH monitoring all have significant limitations in identifying patients who will respond to antireflux therapy. OBJECTIVE: To evaluate the merit of empiric omeprazole therapy in patients with posterior laryngitis. METHODS: Twenty-two patients (11 men/11 women, median age 58 yr) with newly diagnosed posterior laryngitis were enrolled. All had persistent laryngeal symptoms for at least 1 month. An empiric trial of omeprazole at 40 mg q.h.s. was given for 8 wk. Four laryngeal symptoms (hoarseness, throat burning/pain, throat clearing, and cough) and four esophageal symptoms (heartburn, regurgitation, dysphagia, and odynophagia) were scored from 0 to 3. Symptom scores were obtained before, 4 wk after, and 8 wk after the start of omeprazole. Patients were classified as responders if they were symptom free or satisfied with results. Omeprazole was stopped in the responders to look for relapse. Ambulatory pH monitoring was performed in patients who did not respond. RESULTS: One patient discontinued omeprazole and withdrew from the study. In the remaining 21 patients, the total laryngeal and esophageal symptom scores significantly improved after empiric omeprazole. Fourteen patients (67%) were classified as responders. Eight patients (38%) had a relapse when omeprazole was stopped. Six patients (29%), interestingly, did not relapse and did not require long-term antireflux therapy. Seven patients (33%) were classified as nonresponders. Ambulatory pH monitoring was abnormal in four of the five patients who agreed to have this test. Increasing the dose of omeprazole to 40 mg b.i.d. provided no additional benefit in the nonresponders. CONCLUSIONS: Empiric omeprazole therapy is a reasonable, initial approach to patients with suspected gastroesophageal reflux-related posterior laryngitis. A significant number of patients do well with a short course of antireflux therapy. Additionally, a third of the patients may not completely respond to intensive medical therapy despite the fact that reflux is documented.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9399745&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effects of proton pump inhibitors on thyroid hormone metabolism in rats: a comparison of UDP-glucuronyltransferase induction.

Masubuchi N, Hakusui H, Okazaki O.

Drug Metabolism and Analytical Chemistry Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan. XLB05644 niftyserve.or.jp

The effects of proton pump inhibitors on thyroid hormone metabolism in rats were examined. Pantoprazole, omeprazole, and lansoprazole were administered repeatedly to female SD rats at doses of 5, 50, and 300 mg/kg/day for 1 week, and changes in UDP-glucuronyltransferase activities were examined. Increases in o-aminophenol UDP-glucuronyltransferase activity, which was measured as that responsible for the glucuronidation of thyroxine, were evident following 7-day high-dose administration of all the proton pump inhibitors tested. Of the three proton pump inhibitors investigated, o-aminophenol UDP-glucuronyltransferase activity was greatest following the high-dose administration of omeprazole. Androsterone UDP-glucuronyltransferase activity in rats treated with the proton pump inhibitors increased significantly, but these increases were smaller than those of o-aminophenol UDP-glucuronyltransferase. Pantoprazole and omeprazole treatment did not affect plasma T4 or T3 significantly, whereas lansoprazole treatment produced marked reductions in plasma T4 but did not affect plasma T3 significantly. After administration of 125I-labeled thyroid hormone to rats treated with the proton pump inhibitors, biliary excretion of radioactivity increased significantly in omeprazole- and lansoprazole-treated rats; these increases were attributed to induction of liver thyroxine UDP-glucuronyltransferase activities. The order of biliary excretion of radioactivity, as well as the o-aminophenol UDP-glucuronyltransferase activity, in the treated animals was: omeprazole > lansoprazole > pantoprazole. Therefore, repeated administration of the proton pump inhibitors increased thyroxine-metabolizing activity via induction of UDP-glucuronyltransferase, and this induction by pantoprazole was less pronounced than that by omeprazole or lansoprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9416973&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Lansoprazole and ethanol metabolism: comparison with omeprazole and cimetidine.

Battiston L, Tulissi P, Moretti M, Pozzato G.

Institute of Clinical Medicine, University of Trieste, Italy.

Since some antisecretory drugs such as cimetidine and ranitidine, interfere with ethanol metabolism by inhibition of hepatic and/or gastric alcohol dehydrogenase, we investigated the effect of lansoprazole, a new protonic pump inhibitor, on gastric and hepatic alcohol dehydrogenase activity. We also compared the lansoprazole effect with that of omeprazole and cimetidine, respectively. Ethanol blood concentration after oral intake or intravenous administration of ethanol was estimated either in normal male human volunteers or in male rats before and after one week pretreatment with lansoprazole, omeprazole and cimetidine. Furthermore, the in vitro effect of these drugs was studied on both human and rat gastric and hepatic alcohol dehydrogenases. Finally, we measured the effect of the treatment on the reduced hepatic glutathione to test the effects of the drugs on first-pass metabolism of ethanol. The results reported in this paper indicate that lansoprazole, as well as omeprazole, does not affect ethanol metabolism, and that protonic pump inhibitors seem to be safer than imidazole-derived drugs in subjects unable to reduce ethanol intake during conditions requiring acid secretion inhibition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9444664&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effect of the H, K-ATPase inhibitor, esomeprazole magnesium, on gut total antioxidant capacity in mice.

Koch TR, Petro A, Darrabie M, Opara EC.

Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 9200 West Wisconsin Ave., Milwaukee, WI 53295, USA. TimKoch worldnet.att.net

Antioxidant depletion is believed to be a mechanism involved in the pathophysiology of several upper gastrointestinal disorders, and H, K-ATPase inhibitors can alter free radical production by neutrophils. We hypothesized that the H, K-ATPase inhibitor esomeprazole magnesium would decrease gut free radical production with a concomitant increase in gut total antioxidant capacity. A/J mice (n = 10/group) received either vehicle (control) or one of three concentrations of esomeprazole magnesium in vehicle by once-daily gavage for 10 days. Using tissue extracts from stomach and colon, total antioxidant capacity, lipid peroxide levels, and constitutive Cu/Zn-superoxide dismutase were measured using validated assays. There was a dose-related increase in total antioxidant capacity (analysis of variance, P < 0.001) in stomach, but there was no change in the colon. In the assessment of free radical production, there was a trend toward decreased lipid peroxide levels in stomach from mice receiving esomeprazole. In stomach, Cu/Zn-superoxide dismutase activity was increased (ANOVA: p=.03) in mice receiving esomeprazole. In conclusion, gastric total antioxidant capacity and Cu/Zn-superoxide dismutase activity are increased by esomeprazole, and these changes may result in part from decreased free radical production. The present results support the notion that the pharmacological effects of this agent on upper intestinal tissue are more complex than previously thought, and appear to involve both enzymatic and nonenzymatic tissue antioxidants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15350983&dopt=Abstract omeprozole Prilosec