omeprazole, Prilosec
The effect of omeprazole on human natural killer cell activity.

Aybay C, Imir T, Okur H.

Gazi University, Faculty of Medicine, Department of Microbiology, Besevler, Ankara, Turkey.

1. Omeprazole, an antiulcer drug, inhibits the gastric acid pump via blocking the parietal cell (H+ + K+)-ATPase. Omeprazole was also reported to have an inhibitory action on polymorphonuclear neutrophil activities. In the present study the potential effect of omeprazole on human natural killer cell (NK) activity was investigated. 2. Omeprazole decreased NK cytotoxic activity in a dose-dependent manner. 3. Degraded omeprazole showed a similar action. 4.In vitro NK inhibitory action of omeprazole and its acid-degraded form was observed at the concentrations equal and higher than 18 microM (micromolar). 5. NK inhibitory action of omeprazole was recovered to 75% by washing away of the agent. 6. Omeprazole decreased the conjugate formation of effector and target cells by 50% at the concentration of 288 microM

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7590140&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Omeprazole does not reduce gastroesophageal reflux: new insights using multichannel intraluminal impedance technology.

Tamhankar AP, Peters JH, Portale G, Hsieh CC, Hagen JA, Bremner CG, DeMeester TR.

Department of Surgery, University of Southern California, Los Angeles, California, USA.

Proton pump inhibitors are the mainstay of medical management in gastroesophageal reflux disease. Although they provide relief from most symptoms, reflux may persist. We hypothesize that omeprazole does not reduce the total amount of gastroesophageal reflux but simply alters its pH characteristics. Six asymptomatic volunteers had combined 24-hour impedance pH monitoring before and after 7 days of omeprazole (20 mg BID). Multichannel intraluminal impedance was used to identify reflux episodes, which were classified as acid (pH < 4), weak acid (pH > 4 but decrease > 1 pH unit) and nonacid (pH > 4 and decrease < 1 pH unit) by pH measurements 5 cm above the lower esophageal sphincter (LES). A gastric pH sensor located 10 cm below the LES was used to verify the action of omeprazole. Impedance detected a total of 116 reflux episodes before and 96 episodes after omeprazole treatment. The median number of reflux episodes (18 versus 16, P = 0.4), median duration of reflux episodes (4.7 versus 3.6 minutes, P = 0.5), and total duration of reflux episodes (27.2 versus 42.4 minutes, P = 0.5) per subject were similar before and after omeprazole. Acid reflux episodes were reduced from 63% before to 2.1% after omeprazole (P < 0.0001), whereas nonacid reflux episodes increased (15% to 76%, P < 0.0001). Weak acid reflux episodes did not change (22.4% to 21.8%, P = 1.0). The proportion of reflux episodes greater than pH 4 increased from 37% to 98% (P < 0.0001). In normal subjects, omeprazole treatment does not affect the number of reflux episodes or their duration; rather it converts acid reflux to less acid reflux, thus exposing esophagus to altered gastric juice. These observations may explain the persistence of symptoms and emergence of mucosal injury white on proton pump inhibitor therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15531244&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Prescribing of antacids and ulcer-healing drugs in primary care in the north of England.

Roberts SJ, Bateman DN.

Northern and Yorkshire Regional Drug and Therapeutics Centre, University of Newcastle, UK.

BACKGROUND: This study describes the pharmaco-epidemiology of ulcer-healing therapies in primary care in the north of England. METHODS: Anonymous patient-specific prescribing data were extracted from computerized general practice records for 41 practices. Prescribing prevalences were determined according to patient age, gender and recorded prescription indication, for both antacids and H2-receptor antagonists or omeprazole. RESULTS: During the year of the study, antacids were prescribed for 3.9% of the study population, and H2-receptor antagonists or omeprazole for 3.7%. Rates increased with age, peaking at 99 (antacids) and 87 (H2-receptor antagonists) per 1000 population aged 65-84 years. Antacid prescribing rates for women were over twice those for men amongst those aged 15-34 years. For H2-receptor antagonists, rates were higher in men than women, with the excess attributable to prescribing for ulcer indications, although at all ages prescribing for oesophagitis was more prevalent among women. Of the patients prescribed H2-receptor antagonists or omeprazole, 45% (accounting for 51% of prescription items) had indications which included peptic ulcer or oesophagitis, 42% had gastritis or dyspepsia only (35% items), and in 13% no peptic indication was recorded. For each of antacids and H2-receptor antagonists, the practices had similar prescribing profiles according to patient age and gender, but their absolute levels differed up to two-fold. CONCLUSIONS: Prescribing of antacids and ulcer-healing drugs varies systematically with patient age and gender. Consequently, evaluation of crude prescribing rates, without reference to patient demography, is unreliable as a guide to levels of usage. In general practice, H2-receptor antagonists and omeprazole appear to be over-prescribed for minor indications.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7605853&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Metronidazole, omeprazole and clarithromycin: an effective combination therapy for Helicobacter pylori infection.

Yousfi MM, el-Zimaity HM, al-Assi MT, Cole RA, Genta RM, Graham DY.

Department of Medicine, Veterans Affairs Medical Center, Houston, TX 77030, USA.

BACKGROUND: Successful treatment of Helicobacter pylori infection results in cure of peptic ulcer disease. Multi-drug regimens are needed to cure this infection. We studied the effectiveness and side effect profile of two antibiotics active against Helicobacter pylori, metronidazole and clarithromycin, combined with omeprazole. METHODS: We evaluated a combination therapy for H. pylori infection consisting of metronidazole (500 mg b.d.), omeprazole (20 mg b.d.), and clarithromycin (250 mg b.d.) for 2 weeks, followed by ranitidine 300 mg daily for 4 weeks. RESULTS: Thirty-three patients with documented H. pylori infection were studied. Twenty had previously failed antimicrobial therapy, including one with metronidazole-based triple therapy and eight with macrolide-based therapy (five with clarithromycin-based therapy), and 11 with amoxycillin, tetracycline, and bismuth. H. pylori status was determined by histopathology using the Genta stain and by culture. H. pylori status was determined at entry and 4 weeks after completing antimicrobial therapy. The H. pylori infection was cured in 88% (95% CI = 72%-96%) including 90% of those who had failed previous anti-H. pylori therapies. Mild side effects were reported by 18%. CONCLUSION: We conclude that the combination of metronidazole, omeprazole and clarithromycin is an effective treatment for H. pylori infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7605865&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Healing and relapse rates of duodenal ulcer with omeprazole vs ranitidine.

Ahmed W, Qureshi H, Alam SE, Zuberi SJ.

PMRC Research Centre, Jinnah Postgraduate Medical Centre, Karachi.

The efficacy of omeprazole 20 mg a day was assessed against ranitidine 150 mg twice a day in the healing and relapse of duodenal ulcer. Forty three endoscopically verified cases were allocated to 2 weeks of treatment, which was extended to 4 weeks, if the ulcer persisted on day 15. Two cases were excluded due to deviation from the protocol. Of 41 evaluable cases, 21 received omeprazole and 20 ranitidine. Healing rates with omeprazole and ranitidine at 2 weeks were 71% and 70% respectively which rose to 100% and 90% at 4 weeks (N.S). There was no significant difference in pain relief in two groups. Follow-up endoscopies, in 33 healed cases revealed 100% relapse at 3 months in omeprazole and 79% in ranitidine treated cases (P < 0.05).

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omeprazole, Prilosec
Omeprazole inhibits growth of cancer cell line of colonic origin.

Tobi M, Chintalapani S, Goo R, Maliakkal B, Reddy J, Lundqvist M, Oberg K, Luk G.

Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan, USA.

The direct effects of omeprazole on colonic cells has not been evaluated. Controversy exists regarding the potential adverse effects of omeprazole on cell proliferation. In order to mimic the in vivo situation in the patient treated with omeprazole, proliferation cell culture experiments were performed, monitoring directly the effects of gastrin and omeprazole both alone and in combination. Three colonic cancer cell lines were used, two with neuroendocrine features (NCI-H716, LCC-18) and one (DLD-1) not known to have these features. In these in vitro proliferation experiments, only the NCI-H716 colorectal cancer cell line responded to omeprazole by decreased proliferation (P < 0.05). The effect was concentration dependent shown for all doses of omeprazole used. Gastrin had a statistically significant effect on increasing proliferation in the NCS-H716 cell line alone but only at the highest concentration (10(-6) M). Omeprazole has a cytostatic effect on one of three colorectal cancer cell lines but the mechanism for this effect of omeprazole and its potential role in treatment awaits elucidation.

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omeprazole, Prilosec
Mechanisms of gastric acid secretion in the fetal rabbit.

Yee LF, Andrews KJ, Calaustro EQ, Grady EF, Mulvihill SJ.

Department of Surgery, University of California-San Francisco, USA.

BACKGROUND. The parietal cell specific protein H+/K(+)-adenosine triphosphatase H+/K(+)-ATPase) is responsible for gastric acid secretion in adult mammals; however, its ontogeny and role in fetal acid secretion are unknown. The purpose of this study was twofold: (1) to determine the ontogeny of gastric acid secretion and parietal cell H+/K(+)-ATPase expression in the fetal rabbit and (2) to determine the role of H+K(+)-ATPase in fetal acid secretion. METHODS. For the ontogeny studies 88 fetuses from nine time-mated rabbits were studied at successive gestational ages. Gastric fluid and amniotic fluid pH were measured, and total gastric acid was determined by titration. Gastric microsomal protein was analyzed by Western blot analysis for H+/K(+)-ATPase expression by using a monoclonal antibody to the 94 kd alpha-catalytic subunit. To determine the role of H+/K(+)-ATPase in fetal acid secretion, 37 fetuses at day 26 from four time-mated rabbits were treated with (1) omeprazole (20 mg/kg) injection into the amniotic sac (n = 13), (2) carrier injection (n = 12), or (3) no injection (n = 12). Fetal gastric pH and titratable acid were measured at day 28. RESULTS. Amniotic fluid pH was neutral (7.44 to 7.64) throughout the third trimester. Gastric fluid pH was neutral (7.42 to 7.51) until day 25, when it decreased to 7.16 +/- 0.23 (p < 0.05) and subsequently fell to 5.37 +/- 0.05 by day 30. Titratable gastric acid (micromoles) increased from 0 at day 20 to 54.7 +/- 5.4 by day 30. By use of Western blot analysis and immunohistochemistry, gastric microsomal H+/K(+)-ATPase expression was absent from days 20 through 25 of gestation and first detectable at day 26, with qualitative increases to term. Omeprazole significantly inhibited pH (5.45 +/- 0.13 in controls, 5.56 +/- 0.12 with carrier injection, and 6.01 +/- 0.10 with omeprazole injection; p < 0.05). CONCLUSIONS. These data suggest that (1) gastric acid acid secretion begins at day 25 of gestation and increases to term, (2) gastric microsomal H+/K(+)-ATPase expression is first detectable at day 26 of gestation, and (3) omeprazole inhibits, but does not abolish, gastric acid secretion in the fetal rabbit. We conclude that gastric acid secretion is present before birth in the fetal rabbit and is mediated, in part, by omeprazole-sensitive H+/K(+)-ATPase.

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omeprazole, Prilosec
A randomized crossover study investigating the influence of ranitidine or omeprazole on the pharmacokinetics of cephalexin monohydrate.

Madaras-Kelly K, Michas P, George M, May MP, Adejare A.

Department of Veterans Affairs Medical Center, Boise, Idaho, USA.

Limited data characterize pharmacokinetic interactions between cephalexin and ranitidine, and no data exist for an interaction with proton pump inhibitors. The purpose of this study was to investigate the effects of ranitidine or omeprazole administration on the pharmacokinetics and pharmacodynamics of cephalexin. A randomized single- and multiple-dose crossover study was conducted in healthy subjects ingesting cephalexin before and after steady-state administration of ranitidine or omeprazole. Time-concentration profiles were determined and pharmacokinetic parameters were characterized using noncompartmental methods. Pharmacokinetic data were analyzed in accordance with the two 1-sided test for bioequivalence. The percentage of time that serum concentrations remain above the MIC(90) during the dosing interval (T > MIC(90)) for Streptococcus pyogenes and Staphylococcus aureus associated with the pharmacokinetic profiles was calculated. The coadministration of cephalexin with ranitidine or omeprazole resulted in relatively minor changes in C(max), AUC(infinity), t(1/2), or CL/F. t(max) was significantly prolonged when cephalexin was administered with ranitidine or omeprazole. Suboptimal T > MIC(90) was observed for cephalexin irrespective of acid suppression. Delay in absorption of cephalexin resulted in a decrease in the percentage of T > MIC(90) for certain acid-suppressive regimens and pathogen combinations. With the exception of an increase in t(max), there were no significant pharmacokinetic interactions between cephalexin and ranitidine or omeprazole. Delayed t(max) associated with acid suppression may result in a diminished T > MIC(90).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15545310&dopt=Abstract omeprozole Prilosec