omeprazole, Prilosec
Omeprazole-induced relaxation in rat aorta is partly dependent on endothelium.

Kelicen P, Pekiner C, Sarioglu Y, Uma S.

Department of Pharmacology, Faculty of Pharmacy, Hacettepe University, 06100 Sihhiye, Ankara, Turkey. cpekiner hacettepe.edu.tr

We investigated the effect of omeprazole (1 x 10(-5)-3 x 10(-4)M), an inhibitor of H(+),K(+)-ATPase, on rat aortic rings pre-contracted with phenylephrine (10(-6)M). Omeprazole relaxed the tissue in a concentration-dependent manner. Either removal of the endothelium or incubation with nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 3 x 10(-5)M) significantly attenuated the relaxations. Pre-treatment with L-arginine (10(-3)M), but not with D-arginine, reversed the inhibitory action of L-NAME. Indomethacin (10(-6)M) and tetraethylammonium (TEA, 10(-2)M) did not affect the relaxant responses to omeprazole indicating the lack of involvement of cyclooxygenase products and K(+) channels, respectively. These results suggest a role of NO in the mechanism of action of omeprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12361693&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Intravenous esomeprazole.

Keating GM, Figgitt DP.

Adis International Limited, Mairangi Bay, Auckland, New Zealand. demail adis.co.nz

The proton pump inhibitor esomeprazole comprises the S-isomer of omeprazole. An intravenous formulation of the drug has been developed for use in patients not able to take oral drugs. The level of gastric acid control was similar with intravenous and oral esomeprazole in two studies in healthy volunteers receiving 20 or 40 mg once daily for 5 days. In addition, a similar level of gastric acid control occurred with intravenous esomeprazole 40 mg administered by infusion or injection once daily for 10 days. In healthy volunteers, intravenous esomeprazole provided faster and more effective gastric acid control than intravenous pantoprazole (40 mg once daily for 5 days). In addition, control of basal and pentagastrin-stimulated gastric acid secretion was better with intravenous esomeprazole 40 mg than with intravenous omeprazole 40 mg (single-dose study). Healing rates at 4 weeks were approximate, equals 80% in a well designed study in patients with erosive oesophagitis (n = 246) who received esomeprazole 40 mg once daily intravenously (by injection or infusion) or orally. Intravenous therapy was administered for the first week, after which all patients received oral esomeprazole. Intravenous esomeprazole was generally well tolerated in patients with erosive oesophagitis, with a tolerability profile similar to that of the oral formulation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15059043&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Formulation and in vivo evaluation of omeprazole buccal adhesive tablet.

Choi H, Jung J, Yong CS, Rhee C, Lee M, Han J, Park K, Kim C.

College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Ku, 151-742, Seoul, South Korea.

For the development of omeprazole buccal adhesive tablets, we studied the release and bioavailability of omeprazole delivered by buccal adhesive tablets composed of sodium alginate, hydroxypropylmethylcellulose (HPMC), magnesium oxide and croscarmellose sodium. Croscarmellose sodium enhanced the release of omeprazole from the tablets. The analysis of the release mechanism showed that croscarmellose sodium changed the release profile of omeprazole from first- to zero-order release kinetics by forming porous channels in the tablet matrix. However, it decreased the bioadhesive forces and stability of omeprazole tablets in human saliva. The tablet is composed of omeprazole-sodium alginate-HPMC-magnesium oxide-croscarmellose sodium (20:24:6:50:10 mg). It may be attached to the human cheek without collapse and it enhanced the stability of omeprazole in human saliva for at least 4 h, giving a fast release of omeprazole. The plasma concentration of omeprazole in hamsters increased to reach a maximum of 370 ng/ml at 45 min after buccal administration and remained at the high level of 146-366 ng/ml for 6 h. The buccal bioavailability of omeprazole in hamsters was 13.7+/-3.2%. These results demonstrate that the omeprazole buccal adhesive tablet would be useful to deliver omeprazole which degrades very rapidly in acidic aqueous medium and undergoes hepatic first-pass metabolism after oral administration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10974394&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Proton pump inhibitor therapy: preliminary results of a therapeutic interchange program.

Amidon PB, Jankovich R, Stoukides CA, Kaul AF.

Gastroenterology Section, Veteran's Administration Medical Center, Togus, ME 04330, USA.

OBJECTIVE: To analyze the experience of one Department of Veterans Affairs hospital in treating with lansoprazole all patients with acid-peptic disease requiring proton pump inhibitor therapy, including newly diagnosed patients and those who were previously stabilized on omeprazole. STUDY DESIGN: Retrospective analysis. PATIENTS AND METHODS: We evaluated the charts of 78 patients seen between March 17, 1997, and November 1998 by the Gastroenterology Section at the Togus Veterans Administration Hospital who were diagnosed with acid-peptic disease. RESULTS: Overall, side effects necessitated discontinuation of therapy in 10 (13%) of the lansoprazole-treated patients and none of the omeprazole-treated patients. Nine patients on lansoprazole suffered from persistent diarrhea and were placed on omeprazole, and one had lower back pain and was switched to cimetidine therapy. Additionally, 12 patients (15%) had their lansoprazole therapy discontinued because of lack of efficacy. Of the 78 lansoprazole-treated patients, 22 (28%) failed to respond to treatment. CONCLUSIONS: Although this study represents preliminary findings and the statistics are observational in nature, important lessons can be learned. At this particular institution, the potential 12% savings from a mandated therapeutic interchange program were quickly offset by the overall lansoprazole-associated failure rate of 28%. The reproducibility of these preliminary results from an omeprazole-to-lansoprazole therapeutic interchange program in other institutions is unknown but warrants further consideration and additional studies, including those evaluating cost efficacy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10977467&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Clinical and humanistic outcomes in patients with gastroesophageal reflux disease converted from omeprazole to lansoprazole.

Nelson WW, Vermeulen LC, Geurkink EA, Ehlert DA, Reichelderfer M.

Center for Drug Policy and Clinical Economics, University of Wisconsin Hospital and Clinics, 600 Highland Ave, 1530, CSC F6/133, Madison, WI 53792, USA. lc.vermeulen hosp.wisc.edu

BACKGROUND: Omeprazole and lansoprazole are 2 proton pump inhibitors (PPIs) currently available in the United States. Both PPIs are approved for the treatment of gastroesophageal reflux disease (GERD) and are commonly converted in therapeutic interchange programs. OBJECTIVE: To measure clinical and humanistic outcomes in patients with GERD converted from treatment with omeprazole to treatment with lansoprazole through a managed care plan policy. METHODS: Patients with heartburn or GERD receiving omeprazole covered by a local health plan were surveyed by telephone. Data collected included symptom frequency, severity, over-the-counter heartburn preparation use, diet, lifestyle, and overall satisfaction. Patients were then converted to therapy with lansoprazole and again interviewed after at least 30-day use of the new PPI. Demographic data were obtained from the health plan database for analysis. RESULTS: A total of 105 patients completed both telephone surveys. After the conversion, 37% of the patients experienced more frequent symptoms while awake. Symptom severity score was significantly higher (more severe) after conversion (mean score of 1.34 vs 2.26). Thirty-three percent of study patients consumed more over-the-counter heartburn preparations, and 13% changed their diet more frequently due to heartburn symptoms after conversion. Overall patient satisfaction score decreased significantly (less satisfied) after conversion (mean score of 9.0 vs 7.2). There were no significant differences in alcohol and tobacco consumption before and after conversion, while patients consumed significantly less caffeine after conversion. CONCLUSIONS: After the PPI therapeutic interchange from omeprazole to lansoprazole, patients with GERD or heartburn previously stabilized while receiving omeprazole experienced more severe symptoms and expressed decreased patient satisfaction. These results suggest a need to monitor symptoms after similar interchange programs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10979061&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effects of omeprazole on intragastric pH and plasma gastrin are dependent on the CYP2C19 polymorphism.

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

Center of Gastroenterology, Departments of Surgery and Medicine, Clinical Research Center, Huddinge University Hospital, Stockholm, Sweden.

BACKGROUND & AIMS: Omeprazole is metabolized by cytochrome P450 (CYP2C19). The activity of this enzyme is polymorphic, with incidences of poor metabolizers (PMs), heterozygous extensive metabolizers (EMs), and homozygous EMs in white populations of 3%, 30%, and 67%, respectively. The importance of the CYP2C19 polymorphism for the effects of omeprazole on intragastric pH and plasma gastrin concentrations has been investigated. METHODS: Twenty-five white patients were genotyped for CYP2C19 by allele-specific polymerase chain reaction amplification, and their Helicobacter pylori status was assessed by serology and with immunoblot analysis. Intragastric pH was monitored over 24 hours, and meal-stimulated plasma gastrin concentration was measured over 4 hours (AUC 4h) before (day 0) and during (day 8) treatment with 20 mg omeprazole once daily. RESULTS: Eleven patients were homozygous for the wild-type allele (wt/wt), 12 were heterozygous EMs (wt/mut), and 2 were PMs (mut/mut). Median (95% confidence interval) 24-hour intragastric pH in the heterozygous EM group was 5.5 (range, 5.1-5. 9) compared with 3.1 (range, 2.7-3.6) in homozygous EMs (P < 0.0001) at day 8. The percentage of time with intragastric pH > 4 at day 8 was significantly higher in the wt/mut than wt/wt group (72.4% vs. 37.1%; P < 0.0001). H. pylori status had less influence than CYP2C19 on intragastric acidity. Omeprazole treatment increased meal-stimulated plasma gastrin concentrations from day 0 to day 8 in the homozygous EMs and heterozygous EMs by 16% (NS) and 157% (P = 0. 002), respectively. In heterozygous EMs, the gastrin increase was more pronounced in the H. pylori-positive group (226%) than H. pylori-negative group (80%; P = 0.02). CONCLUSIONS: The effects of omeprazole on intragastric pH and plasma gastrin are dependent on the CYP2C19 polymorphism in patients with acid-related disorders.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10982760&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Ingestion of guar-gum hydrolysate partially restores calcium absorption in the large intestine lowered by suppression of gastric acid secretion in rats.

Hara H, Suzuki T, Kasai T, Aoyama Y, Ohta A.

Department of Bioscience and Chemistry, Faculty of Agriculture, Hokkaido University, Sapporo, Japan. hara chem.agr.hokudai.ac.jp

We examined the effects of feeding guar-gum hydrolysate (GGH), a highly fermentable form of dietary fibre with low viscosity, on Ca absorption in the small and large intestines in rats under conditions in which gastric acid secretion was suppressed by a proton pump inhibitor, omeprazole. We also examined the role of the caecum in influencing these effects. The study was designed in a 2 x 2 x 2 factorial arrangement with two diet (GGH-containing (50 g/kg diet) and GGH-free diets) groups, two injection (omeprazole and vehicle) groups and two operation (sham and caecectomy) groups. Apparent Ca absorption was lower in rats administered omeprazole (30 mg/kg body weight per d) for 8 d than in rats administered the vehicle. Ingestion of GGH led to partial restoration of Ca absorption decreased by omeprazole treatment. However, this increment in Ca absorption was not sufficient to meet requirements because the dietary Ca level (3.0 g/kg diet) was the minimum requirement for the intact rats. The small increment in Ca absorption caused by the GGH diet was completely abolished by caecectomy. Soluble Ca pools in the caecal and colonic contents were increased by feeding GGH, and the soluble Ca concentrations were much higher than the Kt values of the Ca active transport system in the large intestine or the serum Ca concentration. These findings suggest that Ca solubilization is not a limiting factor for Ca absorption in the large intestine. Apparent Mg absorption was clearly lower in caecectomized rats than in sham-operated rats, and higher in the GGH-fed groups than in the groups fed on the GGH-free diet, even in the case of caecectomized rats. We conclude that Ca absorption lowered by inhibition of gastric acid secretion is partially restored in rats fed with GGH, but the increment is not sufficient to meet requirements.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10999019&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
The rates of common adverse events reported during treatment with proton pump inhibitors used in general practice in England: cohort studies.

Martin RM, Dunn NR, Freemantle S, Shakir S.

University of Bristol, Department of Social Medicine, Canynge Hall, Whiteladies Road, Bristol, UK. richard.martin bristol.ac.uk

AIMS: To estimate the rates of common adverse events in patients treated with the proton pump inhibitors omeprazole, lansoprazole and pantoprazole in general practice in England. METHODS: In prescription-event monitoring cohort studies, data on dispensed prescriptions prescribed by general practitioners in England soon after each drug was launched were linked to subsequent clinical events recorded by the prescriber. 16 205 patients prescribed omeprazole between June 1989 and June 1990, 17 329 patients prescribed lansoprazole between May and November 1994, and 11 541 patients prescribed pantoprazole between December 1996 and June 1997 were studied. RESULTS: The commonest adverse events in the omeprazole, lansoprazole and pantoprazole cohorts were diarrhoea (incidence: 0. 18, 0.39 and 0.23 per 1000 days of exposure, respectively); nausea/vomiting (incidence: 0.16, 0.22 and 0.18 per 1000 days of exposure, respectively); abdominal pain (incidence: 0.17, 0.21 and 0. 17 per 1000 days of exposure, respectively); and headache (incidence rates: 0.10, 0.17 and 0.15 per 1000 days of exposure, respectively). The remaining adverse events occurred at rates of less than 0.11 per 1000 days of exposure. There were little absolute differences in the rates of most events between the three proton pump inhibitors. However, diarrhoea was more commonly associated with lansoprazole compared with omeprazole (rate difference: 0.21 per 1000 days of exposure; 95% CI 0.17, 0.25; rate ratio: 2.11; 1.78, 2.51), and there was a clear age-response relationship. CONCLUSIONS: Adverse events occurred relatively infrequently in all three cohorts. There were only small absolute differences in event rates between the three drugs, although these data suggest the hypothesis that lansoprazole is associated with more frequent occurrence of diarrhoea, particularly in the elderly.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11012560&dopt=Abstract omeprozole Prilosec