omeprazole, Prilosec
Treatment of Helicobacter pylori infection with a combination of itraconazole and omeprazole.

Keller IJ, van der Hulst RW, Tytgat GN.

Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.

AIM: To determine the in vivo anti-microbial activity of a high-dose itraconazole and omeprazole regimen against Helicobacter pylori. METHODS: In an open pilot study, 10 H. pylori positive dyspeptic patients were treated with itraconazole 200 mg b.d. and omeprazole 200 mg b.d. for 7 days. Follow-up upper gastrointestinal endoscopy was performed 4-5 weeks after completion of therapy. Eradication of H. pylori infection was determined by histopathological examination and culture of biopsies from the antrum and corpus. RESULTS: Eradication was not observed in any patient. CONCLUSION: This combination of itraconazole with omeprazole does not eradicate H. pylori infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7654896&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs.

Luciani F, Spada M, De Milito A, Molinari A, Rivoltini L, Montinaro A, Marra M, Lugini L, Logozzi M, Lozupone F, Federici C, Iessi E, Parmiani G, Arancia G, Belardelli F, Fais S.

Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Nazionale dei Tumori, Milan, Italy.

BACKGROUND: Resistance to antitumor agents is a major cause of treatment failure in patients with cancer. Some mechanisms of tumor resistance to cytotoxic drugs may involve increased acidification of extracellular compartments. We investigated whether proton pump inhibitors (PPIs), currently used in the anti-acid treatment of peptic disease, could inhibit the acidification of the tumor microenvironment and increase the sensitivity of tumor cells to cytotoxic agents. METHODS: We pretreated cell lines derived from human melanomas, adenocarcinomas, and lymphomas with the PPIs omeprazole, esomeprazole, or pantoprazole and tested their response to cytotoxic drugs in cell death assays. We also evaluated extracellular and intracellular pH and vacuolar-H+-ATPase (V-H+-ATPase) expression, distribution, and activity in PPI-pretreated cells by using western blot analyses, immunocytochemistry, laser scanning confocal analysis, and bioluminescence assays. Finally, we evaluated human melanoma growth and cisplatin sensitivity with or without omeprazole pretreatment in xenografted SCID/SCID mice. RESULTS: PPI pretreatment sensitized tumor cell lines to the effects of cisplatin, 5-fluorouracil, and vinblastine, with an IC50 value reduction up to 2 logs. PPI pretreatment was associated with the inhibition of V-H+-ATPase activity and increases in both extracellular pH and the pH of lysosomal organelles. PPI pretreatment induced a marked increase in the cytoplasmic retention of the cytotoxic drugs, with clear targeting to the nucleus in the case of doxorubicin. In in vivo experiments, oral pretreatment with omeprazole was able to induce sensitivity of human solid tumors to cisplatin. CONCLUSION: Our results open new possibilities for the treatment of drug-resistant tumors through combination strategies based on the use of well-tolerated pH modulators such as PPIs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15547183&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Administration of omeprazole to rats for one year produces reciprocal effects on antral gastrin and somatostatin cells and no effect on endocrine cells in the colon.

Sundler F, Andersson K, Mattsson H.

Department of Medical Cell Research, University of Lund, Sweden.

Inhibition of acid secretion with high doses of antisecretagogues, such as omeprazole, is known to raise the plasma gastrin levels. In the present study, we examined the effect of long-term (1-year) treatment of female rats with high doses of omeprazole on the density of antral gastrin and somatostatin cells. A possible effect on the endocrine cell density (chromogranin A as marker) and mucosal thickness of the colon was also examined. The plasma gastrin level in the omeprazole-treated rats was increased 15-fold compared with the level in the controls. The gastrin cell density, on the other hand, showed only a 2-fold increase. The somatostatin cell density in the omeprazole-treated rats was half that in the controls, indicating an inverse relationship between antral gastrin and somatostatin. In the colonic mucosa, neither the mucosal thickness nor the number of chromogranin-A-containing endocrine cells were affected by the omeprazole-induced hypergastrinemia. The results indicate that long-term acid inhibition results in a sustained hypergastrinemia, a modest and stable antral gastrin cell hyperplasia, antral somatostatin cell hypoplasia and lack of trophic effects in the colon.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7657043&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Mechanisms of protection by omeprazole against experimental gastric mucosal damage in rats.

Blandizzi C, Gherardi G, Marveggio C, Natale G, Carignani D, Del Tacca M.

Institute of Medical Pharmacology, School of Medicine and Dentistry, University of Pisa, Italy.

In the present study, the protective effect of omeprazole on gastric mucosa injury induced by ethanol.HCl in rats and the putative mechanisms involved in this action were investigated. Misoprostol and ranitidine were used as reference drugs. The morphometric analysis of histological sections showed that omeprazole caused a significant reduction of mucosal necrotic damage, this effect being associated with a marked increase in Alcian blue recovery from gastric bound mucus. In addition, omeprazole elicited a significant inhibition of gastric acid secretion from pylorus-ligated rats. Misoprostol exerted similar effects to those obtained with omeprazole, even if the Alcian blue recovery and the acid output were affected to a lesser extent. By contrast, ranitidine failed to influence both the mucosal damage and the Alcian blue recovery, while it exerted a marked inhibition on acid secretion. The present results indicate that omeprazole is effective in protecting gastric mucosa from necrotic damage induced by ethanol.HCl and suggest that an enhancement of gastric mucus barrier may account for this protective action.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7657048&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
[In vitro studies on omeprazole metabolism in rat liver microsomes]

[Article in Chinese]

Zhao L, Lou YQ.

Department of Pharmacology, Beijing Medical University.

The metabolism of omeprazole to its two major metabolites, hydroxyomeprazole (OH-OPZ) and omeprazole sulfone (OPZ-SFN) was studied in rat liver microsomes by a reversed phase HPLC assay. The formation of metabolites of OPZ depended on incubation time, substrate concentration, microsomal protein concentration, and was found to be optimal at pH 7.4. The Vmax and Km of OPZ hydroxylation in the rat liver microsomal preparation were 2033 nmol/(min.mg protein) and 46.8 mumol.L-1 respectively. The maximum rate of formation of OPZ-SFN (Vmax) was 187.9 nmol/(min.mg protein), with a Km value of 120.7 mumol.L-1 in rat liver microsome. Moreover, the effects of 7 drugs on OPZ metabolism were tested. The results showed that mephenytoin, benzodiazepines (DZ, NDZ, TMZ, FNZ, NZ) and papaverine caused inhibition of OPZ metabolism, among them papaverine was the only fairly strong inhibitor.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7660792&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Interphenotype differences in disposition and effect on gastrin levels of omeprazole--suitability of omeprazole as a probe for CYP2C19.

Chang M, Tybring G, Dahl ML, Gotharson E, Sagar M, Seensalu R, Bertilsson L.

Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Sweden.

1. Fourteen healthy Swedish Caucasian subjects were given 20 mg of omeprazole orally each morning for 8 days. The subjects included five poor metabolisers (PM) of S-mephenytoin, four heterozygous extensive metabolisers (hetEM) and five subjects with a very rapid metabolism (rapidEM). 2. After the first dose, the relative mean areas under the plasma concentration vs time curve (AUC) of omeprazole in rapidEM, hetEM and PM were 1:3.7:20 (all different, P < 0.001). A similar relation was seen in the AUC(0,10 h) of the sulphone metabolite (1:3:12). Concentrations of hydroxyomeprazole were higher in EM than in PM confirming that the hydroxy, but not the sulphone metabolite, is formed by the S-mephenytoin hydroxylase (CYP2C19). After 8 days of treatment, the differences between groups were similar. 3. After both the first and the eighth doses, the omeprazole/hydroxyomeprazole plasma concentration ratio, determined 3 h after drug intake, correlated with the mephenytoin S/R ratio (rs = 0.94; P < 0.001; n = 14) suggesting that omeprazole might be used to phenotype for CYP2C19. 4. After the first dose of omeprazole, there was no difference in the AUC(0,10 h) of plasma gastrin between the three groups. From the first to the eighth dose, the AUC(0,10) of gastrin increased significantly in both hetEM and PM, while there was no change in the rapidEM. After the eighth dose, the AUC(0,10) of gastrin correlated significantly with the AUC of omeprazole in plasma (rs = 0.79; P < 0.01; n = 13).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7669487&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Increased risk of rebleeding of peptic ulcer bleeding in patients with comorbid illness receiving omeprazole infusion.

Cheng HC, Chuang SA, Kao YH, Kao AW, Chuang CH, Sheu BS.

Department of Internal Medicine, Institute of Clinical Medicine, National Cheng Kung University Hospital, 138, Sheng Li Road, Tainan, Taiwan.

BACKGROUND/AIMS: The study aimed to evaluate whether administration of intravenous omeprazole has different rebleeding rates for peptic ulcer bleeding of patients with and without comorbid illness. METHODOLOGY: A total of 80 patients with peptic ulcer bleeding were enrolled after therapeutic endoscopy to achieve hemostasis. Each patient had received omeprazole 80 mg bolus loading and 40 mg twice daily for three days (total dosage of 320 mg within 3 days). Two subgroups were divided, based on the absence (Group A) or presence (Group B) of one or more comorbid illnesses, such as chronic obstructive pulmonary disease, congestive heart failure, uremia, cirrhosis, diabetes mellitus, and old stroke. The 7-day and 28-day rebleeding rates were recorded. RESULTS: The presence of comorbid illness had a higher rebleeding rate than those without comorbid illness (7-day: 32.5 vs. 2.5%, p < 0.05; 28-day: 37.5 vs. 5.0%, p < 0.05). Patients with two or more comorbid diseases had an even higher risk of rebleeding than those with a single comorbid illness (66.7% vs. 26.5%, p < 0.05). CONCLUSIONS: Low-dose infusion of omeprazole can achieve favorable control of rebleeding in the patients with peptic ulcer bleeding but without comorbid diseases. As patients with comorbid illness had a higher risk of rebleeding, a higher dosage or prolonged duration of omeprazole infusion would be rationally indicated to prevent risk of rebleeding.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14696515&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Evaluation of the effect of lansoprazole in suppressing acid secretion using 24-hour intragastric pH monitoring.

Takeda H, Hokari K, Asaka M.

Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.

The acid-inhibitory effect of lansoprazole was evaluated in comparison with that of famotidine and omeprazole by using 24-h intragastric pH monitoring in 10 young, healthy Japanese volunteers. Lansoprazole 20 mg once daily in the morning was superior to famotidine 20 mg twice daily, omeprazole 20 mg once daily in the morning in reducing 24-h intragastric acidity. Unlike famotidine, whose acid-inhibitory effect was observed mainly at night, both lansoprazole and omeprazole inhibited both daytime and nocturnal acid secretion, with the maximal effect occurring in the afternoon. Although the daily profile of acid-inhibitory action of lansoprazole was similar to that of omeprazole, the acid-inhibitory effect of lansoprazole was more potent than that of omeprazole at any time of the day. These results indicate that lansoprazole at a dosage of 30 mg once daily in the morning produced the most potent inhibition of acid secretion in young Japanese volunteers, compared with famotidine 20 mg twice daily and omeprazole 20 mg once in the morning.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7673616&dopt=Abstract omeprozole Prilosec