omeprazole, Prilosec
Atrophic gastritis during long-term omeprazole therapy affects serum vitamin B12 levels.

Schenk BE, Kuipers EJ, Klinkenberg-Knol EC, Bloemena EC, Sandell M, Nelis GF, Snel P, Festen HP, Meuwissen SG.

Department of Gastroenterology, Free University Hospital, Amsterdam, The Netherlands.

BACKGROUND: Omeprazole maintenance therapy for gastro-oesophageal reflux disease (GERD) has been associated with an increased incidence of atrophic gastritis in H. pylori-infected patients and with a decreased absorption of protein-bound, but not of unbound cobalamin. AIM: : To test the hypothesis that the combination of decreased cobalamin absorption and atrophic gastritis decreases serum cobalamin levels during omeprazole therapy. METHODS: Forty-nine H. pylori-positive GERD patients were treated with omeprazole for a mean (+/- s.d.) period of 61 (25) months. At the start of omeprazole treatment (T0) and at the latest follow-up visit (T1), serum was obtained for measurement of cobalamin. Corpus biopsy specimens were obtained at entry and follow-up for histopathological scoring according to the updated Sydney classification. RESULTS: At inclusion, none of the 49 patients had signs of atrophic gastritis. During follow-up, 15 patients (33%) developed atrophic gastritis, nine of whom had moderate to severe atrophy. These 15 patients did not differ from the other 34 patients with respect to age, serum cobalamin at T0 or the duration of follow-up. During follow-up, no change was observed in the median serum cobalamin level in the 34 patients without atrophy; (T0) 312 (136-716) vs. (T1) 341 (136-839) pmol/L (P=0.1). In the 15 patients who developed atrophy, a decrease in cobalamin was seen from 340 (171 to 787) at baseline to 285 (156-716) at latest follow-up (P < 0.01). CONCLUSIONS: The development of atrophic gastritis during omeprazole treatment in H. pylori-positive GERD patients is associated with a decrease of serum vitamin B12 levels.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10540050&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Prevalence of potential proton-pump inhibitor drug interactions: a retrospective review of prescriptions in community pharmacies.

Saltiel E, Fask A.

Cedars-Sinai Medical Center, Los Angeles, California 90035, USA.

Drug interactions are a major cause of drug-related problems. This study assessed the comparative frequency of potential drug-drug interactions in patients receiving either omeprazole or lansoprazole. We reviewed prescription data from 144 community pharmacies in 25 states for the period of October 12, 1996, through October 20, 1997, from which the rates at which patients received either proton-pump inhibitor concurrently with > or =1 potentially interacting drugs were determined. A total of 7306 patients received only omeprazole, and 2486 received only lansoprazole. In this sample, 722 patients (9.9%) who received omeprazole also received a potentially interacting medication at the same time, compared with 8 patients (0.3%) who received lansoprazole (P<0.001). These data suggest that clinicians should be conscientious when selecting or dispensing drugs for patients taking omeprazole, given the relatively high prevalence of potential drug interactions in clinical practice.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10566575&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Will Helicobacter pylori affect short-term rebleeding rate in peptic ulcer bleeding patients after successful endoscopic therapy?

Lin HJ, Tseng GY, Hsieh YH, Perng CL, Lee FY, Chang FY, Lee SD.

Department of Medicine, Veterans General Hospital-Taipei, Taiwan, Republic of China.

OBJECTIVE: Helicobacter pylori (H. pylori) can augment the pH-increasing effect of omeprazole in patients with peptic ulcer. A high intragastric pH may be helpful in preventing recurrent hemorrhage by stabilizing the blood clot at the ulcer base of bleeding peptic ulcer patients. Therefore, we hypothesized that omeprazole may reduce short-term rebleeding rate in these patients with H. pylori infection after initial hemostasis had been obtained. METHODS: Between July 1996 and December 1998, 65 bleeding peptic ulcer patients (24 gastric ulcer, 41 duodenal ulcer) who had obtained initial hemostasis with endoscopic therapy were enrolled in this trial. Thirty (46.2%) of them were found to have H. pylori infection by a rapid urease test and pathological examination. For all studied patients, omeprazole was given 40 mg intravenously every 6 h for 3 days. Thereafter, omeprazole was given 20 mg per os (p.o.) once daily for 2 months. A pH meter was inserted in the fundus of each patient under fluoroscopic guidance after intravenous omeprazole had been administered. The occurrence of rebleeding episode was observed for 14 days. RESULTS: In patients with H. pylori infection, intragastric pH (median, 95% confidence interval [CI]: 6.54, 5.90-6.68) was higher than in those without H. pylori infection (6.05, 5.59-6.50, p < 0.001). However, the patients with rebleeding (2 vs 3), volume of blood transfusion (median, range: 1000 ml, 0-2250 vs 750, 0-2000), number of operations (0 vs 1), mortality caused by bleeding (0 vs 0), and hospital stay (median, range: 6 days, 3-14 vs 7, 5-16) were not statistically different from those without H. pylori infection. CONCLUSIONS: Omeprazole does increase intragastric pH in bleeding peptic ulcer patients with H. pylori infection. However, the presence of H. pylori infection does not affect the short-term rebleeding rate in these patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10566712&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
CYP2C19 genotype-related efficacy of omeprazole for the treatment of infection caused by Helicobacter pylori.

Tanigawara Y, Aoyama N, Kita T, Shirakawa K, Komada F, Kasuga M, Okumura K.

Department of Hospital Pharmacy, School of Medicine, Kobe University, Japan.

OBJECTIVES: Omeprazole is used for the treatment of infection caused by Helicobacter pylori, and it is metabolized by the polymorphic cytochrome P4502C19 (CYP2C19). We have found that the anti-H pylori efficacy by the combination of omeprazole and antibiotics is related to the CYP2C19 genotype. METHODS: One hundred eight patients with cultured H pylori-positive gastritis or peptic ulcer were treated with three regimens: quadruple treatment without proton pump inhibitors (n = 25), dual treatment with omeprazole and amoxicillin (INN, amoxicilline) (n = 26), and triple treatment with omeprazole, amoxicillin, and clarithromycin (n = 57). The CYP2C19 genotype was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and the assessment of the eradication of H pylori was based on all negative examinations, including culture, histology, and 13C-urea breath test. RESULTS: The eradication rates for the extensive metabolizers were 50% and 86% for the dual and triple treatments, respectively. In contrast, all of the poor metabolizers treated with omeprazole and antibiotics (n = 15) showed an eradication of H pylori. CONCLUSION: The anti-H pylori effect of dual treatment is highly efficient for CYP2C19 poor metabolizers, which suggests that clarithromycin is not necessary as a first line of therapy for this type of patients. Genotyping can provide a choice for the optimal regimen based on individual CYP2C19 genotype.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10579481&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Stereospecific analysis of omeprazole supports artemisinin as a potent inducer of CYP2C19.

Mihara K, Svensson US, Tybring G, Hai TN, Bertilsson L, Ashton M.

Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge University Hospital, Sweden.

The purpose of the study was to determine the enantiomer pharmacokinetics of omeprazole and 5-hydroxy-omeprazole before and after administration of the antimalarial artemisinin to confirm artemisinin's ability to induce CYP2C19. Nine healthy male Vietnamese subjects were given a single 20 mg dose of omeprazole orally 1 week before (day - 7) artemisinin administration. Artemisinin was then given orally (500 mg) for 7 days (days 1-7). On days 1 and 7, a single 20 mg dose of omeprazole was coadministered with artemisinin. After a washout period of 6 days, a single 20 mg dose of omeprazole was again administered together with a single 500 mg of artemisinin (day 14). Stereoselective pharmacokinetics of omeprazole and 5-hydroxyomeprazole was determined on days of omeprazole administration. Seven days of artemisinin administration significantly decreased the AUC of both omeprazole enantiomers (day 7), compared with day 1 (P < 0.001). All values were normalized after the washout period. Artemisinin increased the AUC ratio of R-5-hydroxyomeprazole/R-omeprazole significantly (P < 0.01) on day 7. The AUC ratio of omeprazole sulphone/S-omeprazole did not differ between study days. Artemisinin decreased the AUC of S-omeprazole to the same extent as that of R-omeprazole in extensive CYP2C19 metabolizers. suggesting that artemisinin induces a different enzyme in addition to CYP2C19. These results support and strengthen earlier findings that artemisinin induces CYP2C19 as well as at least one enzyme other than CYP3A4.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10626755&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Pyruvate decarboxylase, the target for omeprazole in metronidazole-resistant and iron-restricted Tritrichomonas foetus.

Sutak R, Tachezy J, Kulda J, Hrdy I.

Department of Parasitology, Charles University, Vinicna 7, 128 44 Prague 2, Czech Republic.

The substituted benzimidazole omeprazole, used for the treatment of human peptic ulcer disease, inhibits the growth of the metronidazole-resistant bovine pathogen Tritrichomonas foetus in vitro (MIC at which the growth of parasite cultures is inhibited by 50%, 22 microg/ml [63 microM]). The antitrichomonad activity appears to be due to the inhibition of pyruvate decarboxylase (PDC), which is the key enzyme responsible for ethanol production and which is strongly upregulated in metronidazole-resistant trichomonads. PDC was purified to homogeneity from the cytosol of metronidazole-resistant strain. The tetrameric enzyme of 60-kDa subunits is inhibited by omeprazole (50% inhibitory concentration, 16 microg/ml). Metronidazole-susceptible T. foetus, which expresses very little PDC, is only slightly affected. Omeprazole has the same inhibitory effect on T. foetus cells grown under iron-limited conditions. Similarly to metronidazole-resistant cells, T. foetus cells grown under iron-limited conditions have nonfunctional hydrogenosomal metabolism and rely on cytosolic PDC-mediated ethanol fermentation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15155220&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effect of omeprazole on gastric adenosine A1 and A2A receptor gene expression and function.

Yip L, Leung HC, Kwok YN.

Department of Physiology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.

Adenosine has been shown to inhibit immunoreactive gastrin (IRG) release and to stimulate somatostatin-like immunoreactivity (SLI) release by activating adenosine A(1) and A(2A) receptors, respectively. Since the synthesis and release of gastrin and somatostatin are regulated by the acid secretory state of the stomach, the effect of achlorhydria on A(1) and A(2A) receptor gene expression and function was examined. Omeprazole-induced achlorhydria was shown to suppress A(1) and A(2A) receptor gene expression in the antrum and corporeal mucosa, but not in the corporeal muscle. Omeprazole treatment produced reciprocal changes in A(1) receptor and gastrin gene expression, and parallel changes in A(2A) receptor and somatostatin gene expression. The localization of A(1) and A(2A) receptors on gastrinsecreting G-cells and somatostatin-secreting D-cells, respectively, suggests that changes in adenosine receptor expression may modulate the synthesis and release of gastrin and somatostatin. Thus, the effect of omeprazole on adenosine receptor-mediated changes in IRG and SLI release was also examined in the vascularly perfused rat stomach. After omeprazole treatment, the A(1) receptor-mediated inhibition of IRG and SLI release induced by N(6)-cyclopentyladenosine (A(1) receptor-selective agonist) was not altered, but the A(2A) receptor-mediated augmentation of SLI release induced by 2-p-(2-carboxyethyl-)phenethylamino-5'-N-ethylcarboxamidoadenosine (A(2A)-selective agonist) was significantly attenuated. These findings agree well with the corresponding omeprazole-induced decrease in antral A(2A) receptor mRNA expression. Overall, the present study suggests that adenosine receptor gene expression and function may be altered by omeprazole treatment. Acid-dependent changes in adenosine receptor expression may represent a novel purinergic regulatory feedback mechanism in controlling gastric acid secretion.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15155771&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Gastric mucosal lesions in dogs with acute intervertebral disc disease: characterization and effects of omeprazole or misoprostol.

Neiger R, Gaschen F, Jaggy A.

Small Animal Hospital, Faculty of Veterinary Medicine, University of Bern, Switzerland. rneiger rvc.ac.uk

We characterized gastric mucosal lesions in dogs with acute degenerative disc disease treated by surgery and corticosteroid administration. The effect of omeprazole and misoprostol on gastric lesions in these dogs was also evaluated. Dogs were randomly assigned to 1 of 2 treatment groups or to the control group. Treatment consisted of omeprazole at 0.7 mg/kg orally once daily, or misoprostol at 2 microg/kg orally 3 times daily. All 3 groups received dexamethasone at 2 mg/kg on day 0, prednisolone at 2 mg/kg on day 1. prednisolone at 1 mg/kg on day 2, and prednisolone at 0.5 mg/kg on all further days (range, 5-6 days). Endoscopic examination was performed on day 0 and 5-6 days later. Four regions of the stomach were qualitatively scored from 1 to 12 based on the presence of submucosal hemorrhage, erosion, or ulceration, with ulceration receiving the highest numerical score. Nineteen of 25 dogs had gastric mucosal lesions at the beginning of the study. No significant difference was found in the gastric lesion score among the 3 groups at the end of the study. Gastric mucosal lesions were concluded to be common in dogs with acute degenerative disc disease treated with corticosteroids. Neither omeprazole nor misoprostol at the doses used was effective in healing or preventing the further development of gastric mucosal lesions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10668814&dopt=Abstract omeprozole Prilosec