omeprazole, Prilosec
Gastrin-mediated effects of omeprazole on rat colon mucosa.

Klingensmith ME, Neville LJ, Delpire E, Wolfe MM, Soybel DI.

Department of Surgery, Brigham and Women's Hospital, Boston, Mass., USA.

BACKGROUND: Omeprazole increases circulating gastrin levels, which in turn may affect the growth and differentiation of colon mucosa. Chloride transport mechanisms in normal colon were analyzed as markers for possible trophic actions of endogenous hypergastrinemia. METHODS: Four groups of Fischer rats were studied for 10 days. Group 1 (baseline) received no treatment. Group 2 received omeprazole only. Group 3 received omeprazole plus vehicle. Group 4 received omeprazole plus CCK-B gastrin receptor antagonist (GRA) L740,093 in vehicle. On day 10 serum gastrin was assayed. Colon mucosa was analyzed for protein and DNA content. Semiquantitative Northern analysis measured levels of messenger RNA (mRNA) encoding for key Cl- transporters: Na-K-Cl cotransporter (Cl- secretion in crypts), Cl-/HCO3- exchanger (Cl- absorption in villi), and Na/K adenosine triphosphatase (not directly involved in Cl- transport). RESULTS: Omeprazole increased gastrin levels, which were not altered by vehicle or GRA. Omeprazole increased protein, DNA, and Na/K adenosine triphosphatase mRNA levels, with no effect by GRA. In contrast, omeprazole decreased Na-K-Cl and Cl-/HCO3- mRNA levels, effects that were partly reversed by GRA. CONCLUSIONS: Omeprazole augments growth index values of colon mucosa independent of serum gastrin. Against a background of omeprazole-induced achlorhydria hypergastrinemia appears to influence differentiation rather than growth of normal colon mucosa.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10455894&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effect of splitting the dose of esomeprazole on gastric acidity and nocturnal acid breakthrough.

Hammer J, Schmidt B.

Abteilung fur Gastroenterologie und Hepatologie, Universitatsklinik fur Innere Medizin IV, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. johann.hammer univie.ac.at

BACKGROUND: Twice-daily dosing is increasingly used to improve gastric acid control, although not all proton-pump inhibitors are more effective when doses are split. Standard dose esomeprazole provides better gastric acid control than other standard dose proton-pump inhibitors. AIMS: To compare the effect of standard dose esomeprazole (1 x 40 mg) with 20 mg b.d. on gastric acidity. METHODS: Thirteen healthy subjects participated in this crossover study, receiving esomeprazole 2 x 20 mg and 1 x 40 mg for 7 days in random order with a washout period of at least 7 days. Gastric 24-h pH was measured on days 1, 2 and 6. RESULTS: Median gastric 24-h pH was higher during 2 x 20 mg esomeprazole on day 2 (P < 0.01), no differences were detected on day 6. Night-time gastric acid suppression was significantly improved by 2 x 20 mg esomeprazole on all study days (P < 0.05). Nocturnal acid breakthrough was observed on all study days in subjects receiving 1 x 40 mg, but in only 85% (first night), 64% (second night), and 45% of subjects (sixth night) with 2 x 20 mg (P < 0.05). CONCLUSION: Splitting the esomeprazole dose improves initial acid suppression, this effect starts at the first night. Maximal benefit is achieved on day 2, while the effect on night-time acid control is detectable during the entire first week of treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15142200&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Correlation between acid secretion and proton pump activity during inhibition by the proton pump inhibitors omeprazole and pantoprazole.

Nishioka K, Nagao T, Urushidani T.

Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.

Omeprazole and pantoprazole are known to be irreversible, SH-acting inhibitors of gastric H+,K+-adenosine triphosphatase (H+,K+-ATPase). Both drugs concentration-dependently and pH-dependently inhibited K+-dependent p-nitrophenyl phosphatase (K+-pNPPase) activity in purified rabbit gastric microsomes. The potency of omeprazole was about three times that of pantoprazole in the pH ranges tested. Both drugs also inhibited acid secretion, as determined by [14C]aminopyrine accumulation in isolated rabbit gastric glands, with the potency ratio being about 5 (omeprazole over that of pantoprazole). Under conditions in which acid secretion was inhibited completely by the drugs, the total K+-pNPPase activity in the digitonin-permeabilized glands was scarcely reduced, showing an apparent discrepancy between the acid secretion and the proton pump activity. The isolated glands were stimulated with secretagogues for 30 min in the presence of the inhibitors, homogenized, and then separated into fractions in which K+-pNPPase activity was measured. Omeprazole exclusively inhibited the activity in the low-speed fraction, which was rich in the apical membranes, whereas pantoprazole did not inhibit activity in any fraction. When the time of treatment with the inhibitors was increased up to 5 hr, the inhibition of the total K+-pNPPase activity in the glands reached a plateau at an inhibition rate lower than 50% within 2 hr. This suggested that no continuous recycling of the proton pump was occurring during stimulation. The inhibitory effect of both drugs on the permeabilized gland preparation was less potent than that on the purified enzyme, especially at the higher pH, and it appeared to be partially reversible. The extent of the reduction in potency was more prominent for pantoprazole. It is concluded that a lower amount of proton pump activity needs to be inhibited by pantoprazole than by omeprazole to achieve the same extent of acid secretion inhibition. This appears to be due to the nature of pantoprazole, i.e. the requirement of low pH for activation and the partial reversibility of the inhibition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10487539&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
The cost-effectiveness of the omeprazole test in patients with noncardiac chest pain.

Ofman JJ, Gralnek IM, Udani J, Fennerty MB, Fass R.

Department of Medicine, Cedars-Sinai Health System, Los Angeles, CA, USA.

PURPOSE: Recent evidence suggests that an empiric trial of omeprazole (the "omeprazole test") is sensitive and specific for diagnosing gastroesophageal reflux disease (GERD) as the cause of noncardiac chest pain. Our objective was to examine the clinical, economic, and policy implications of alternative diagnostic strategies for patients with noncardiac chest pain. METHODS: Decision analysis was used to evaluate the clinical and economic outcomes of two diagnostic strategies that begin with the omeprazole test (60 mg daily for 7 days) followed sequentially by invasive testing utilizing endoscopy, ambulatory 24-hour esophageal pH monitoring, and esophageal manometry as necessary, compared with two traditional strategies involving sequential invasive diagnostic tests. Cost estimates were based on Medicare reimbursement and the Red Book of average wholesale drug prices. Probability estimates were derived from a systematic review of the medical literature. RESULTS: The average cost per patient for the four diagnostic strategies varied from $1,859 to $2,313. Strategies utilizing the initial omeprazole test resulted in 84% of patients being symptom free at 1 year, compared with 73% to 74% for the strategies that began with invasive tests. The strategy of the omeprazole test, followed if necessary by ambulatory pH monitoring, then manometry, and then endoscopy, was both most effective and least expensive. It led to an 11% improvement in diagnostic accuracy and a 43% reduction in the use of invasive diagnostic tests, thus yielding an average cost savings of $454 per patient, compared with the strategy of beginning with endoscopy, then pH monitoring, and then manometry. CONCLUSIONS: Among patients with noncardiac chest pain, diagnostic strategies that begin with the omeprazole test result in reduced costs, improved diagnostic certainty, and a greater proportion of symptom-free patients at 1 year than do traditional strategies that begin with invasive diagnostic tests.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10492314&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Omeprazole, amoxycillin and metronidazole for the cure of Helicobacter pylori infection.

Bayerdorffer E, Lind T, Dite P, Bardhan KD, O'Morain C, Delchier JC, Spiller R, Veldhuyzen van Zanten S, Sipponen P, Megraud F, Zeijlon L.

Medical Department I, Gastroenterology, University Hospital Carl Gustav Carus, Dresden, Germany. Bayerdorffer t-online.de

OBJECTIVE: In two studies, different regimens of omeprazole-amoxycillin-metronidazole were assessed for the eradication of Helicobacter pylori. DESIGN: Randomized, international, multicentre studies with parallel groups. SETTING: The studies were performed at centres in Canada, Czech Republic, France, Germany, Hungary, Sweden and UK. PARTICIPANTS AND INTERVENTIONS: H. pylori-positive patients with duodenal ulcer disease (active or in remission) were randomized to 7-day treatment with: omeprazole 40 mg once daily, amoxycillin 500 mg three times daily and metronidazole 400 mg three times daily (OAMtid; n = 242); omeprazole 20 mg twice daily, amoxycillin 1000 mg twice daily and metronidazole 800 mg twice daily (OAM800; n = 247); or omeprazole 20 mg twice daily, amoxycillin 1000 mg twice daily and metronidazole 400 mg twice daily (OAM400; n = 127). MAIN OUTCOME MEASURES: Eradication of H. pylori. RESULTS: Intention-to-treat analysis revealed H. pylori eradication rates of 76% (184/242) with OAMtid, 80% (198/247) with OAM800, and 76% (97/127) with OAM400. There was considerable variation in the levels of primary resistance to metronidazole in different countries. The overall eradication rate in patients infected with metronidazole-sensitive H. pylori strains was 85% (313/370), compared with 60% (56/94) in patients harbouring metronidazole-resistant strains (P<0.001). All regimens were generally well tolerated, with mild adverse events occurring in 4-26% of patients (mainly diarrhoea, reversible increase in liver enzymes and headache). CONCLUSION: The OAM combination is effective in curing H. pylori infection. Primary metronidazole resistance may reduce its effectiveness, but an increased daily dosing of metronidazole may partly overcome this problem.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10503818&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
The effects of NorA inhibition on the activities of levofloxacin, ciprofloxacin and norfloxacin against two genetically related strains of Staphylococcus aureus in an in-vitro infection model.

Aeschlimann JR, Kaatz GW, Rybak MJ.

Department of Pharmacy Services (1B), and College of Pharmacy and Allied Health Professions, Wayne State University, MI 48201, USA.

NorA is a membrane-associated multidrug efflux protein that can decrease susceptibility to fluoroquinolones in Staphylococcus aureus. We have previously determined that NorA inhibition can increase fluoroquinolone killing activity and post-antibiotic effect. In the current investigation, we studied the killing activity and development of resistance for levofloxacin, ciprofloxacin and norfloxacin with or without the H+/K+ ATPase inhibitor omeprazole, in a wild-type strain of S. aureus (SA-1199) and its NorA hyperproducing mutant (SA-1199-3) in an in-vitro pharmacodynamic model with infected fibrin-platelet matrices. Each drug was administered every 12-24 h for 72 h and human pharmacokinetics were simulated. Levofloxacin was the most potent fluoroquinolone against both strains and its activity was not significantly affected by combination with omeprazole. The addition of omeprazole to ciprofloxacin significantly lowered colony counts at all time-points against both strains and decreased the time to 99.9% kill from 72.2 h to 33.8 h against SA-1199. The addition of omeprazole minimally increased norfloxacin activity against both strains. Omeprazole decreased the frequency of ciprofloxacin resistance nearly 100-fold at the 24 h time-point, but the frequency of resistance was not significantly different for any of the fluoroquinolone regimens after this time-point. No resistance was detected during levofloxacin regimens. The hydrophobic fluoroquinolones such as levofloxacin appear to circumvent NorA efflux, which may contribute to their better activity and decreased resistance rates against staphylococci. More durable and potent NorA inhibitor compounds are needed that can improve killing activity and prevent resistance.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10511401&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Hypericin-induced phototoxicity of human leukemic cell line HL-60 is potentiated by omeprazole, an inhibitor of H+K+-ATPase and 5'-(N,N-dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger.

Mirossay L, Mirossay A, Kocisova E, Radvakova I, Miskovsky P, Mojzis J.

Department of Pharmacology, Faculty of Medicine, Safarik University, Kosice, Slovak Republic. mirossay central.medic.upjs.sk

Hypericin, an antiretroviral and antineoplastic agent, seems to have multiple modes of light-induced biological activity connected with the production of single oxygen and/or excited-state proton transfer and a consequent pH drop of pH formation in the hypericin environment. In the present study omeprazole, an inhibitor of H+K+-ATPase, and amiloride, an inhibitor of the Na+/H+ exchanger, have been used for testing the hypothetical pH decreasing effect of hypericin in its antineoplastic action. The results of our experiments have shown that in the HL-60 cell line the effect of hypericin (10(-6) mol.l(-1)) was significantly potentiated by omeprazole and 5'-(N,N-dimethyl)-amiloride. The effect of omeprazole seemed to be less specific than that of 5'-(N,N-dimethyl)-amiloride. Our results support the hypothesis that the excited-state proton transfer and the consequent acidification of the hypericin environment could play a role in the biological activity of hypericin. Moreover, both omeprazole and 5'-(N,N-dimethyl)-amiloride are effective potentiating agents of hypericin cytotoxic effect in the HL60 cell line.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10534017&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Assessment of patient satisfaction with a formulary switch from omeprazole to lansoprazole in gastroesophageal reflux disease maintenance therapy.

Condra LJ, Morreale AP, Stolley SN, Marcus D.

Department of Pharmacy, Veteran Affairs San Diego Healthcare System, CA 92161, USA. condraljc aol.com

OBJECTIVE: To determine if patients perceived a difference in the efficacy, side effects, and value of omeprazole versus lansoprazole for gastroesophageal reflux disease (GERD) maintenance therapy after a formulary conversion, and to evaluate the costs of the conversion. STUDY DESIGN: An unblinded questionnaire was mailed to patients who were currently receiving GERD maintenance therapy with lansoprazole from the Veterans Affairs San Diego Healthcare System. PATIENTS AND METHODS: Three hundred patients who had been on omeprazole for a minimum of 2 months prior to the formulary conversion and on lansoprazole for a minimum of 2 months after the formulary conversion were surveyed. Patients were asked to rate the severity and frequency of their symptoms (pain, heartburn, and regurgitation) on a scale from 0 to 9 for each medication. Questions regarding side effects, medication preference, and satisfaction with the formulary conversion process were also addressed. RESULTS: Fifty-two percent of the surveys were returned. There was no statistically significant difference between median total symptom scores for omeprazole and lansoprazole (1.33 vs. 1.34, respectively). More patients reported side effects to lansoprazole (P < 0.001) than to omeprazole. Sixty-four percent of patients preferred omeprazole (P < 0.005). The formulary conversion was estimated to save $29,000 per year. CONCLUSIONS: Omeprazole was the medication preferred by patients for GERD maintenance therapy. Patients were willing to pay an additional fee for their preferred agent. Fewer adverse events were reported with omeprazole. The potential cost savings of the formulary conversion may have been at the expense of patient satisfaction.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10537869&dopt=Abstract omeprozole Prilosec