omeprazole, Prilosec
The effect of pentadecapeptide BPC 157, H2-blockers, omeprazole and sucralfate on new vessels and new granulation tissue formation.

Sikiric P, Separovic J, Anic T, Buljat G, Mikus D, Seiwerth S, Grabarevic Z, Stancic-Rokotov D, Pigac B, Hanzevacki M, Marovic A, Rucman R, Petek M, Zoricic I, Ziger T, Aralica G, Konjevoda P, Prkacin I, Gjurasin M, Miklic P, Artukovic B, Tisljar M, Bratulic M, Mise S, Rotkvic I.

Medical and Veterinary Faculty, University of Zagreb, Republic of Croatia.

A clear protection of the gastrointestinal tract and an evident anti-inflammatory effect were shown for a novel stomach pentadecapeptide BPC 157 (i.p./i.g.) in comparison with several reference standards in various ulcer models along with a protection of endothelium and particular interaction with the NO-system. Thus, we evaluated whether this pentadecapeptide along with other gastroprotective agents could affect angiogenesis and the healing process in vivo using a procedure initially described by Szabo and co-workers. In each rat, two sterile sponges (1 x 1 x 0.25 cm; V = 0.25 mL) with the same quantities of BPC 157 (10 ng x mL(-1), 10 microg x mL(-1), 50 microg x kg(-1)) or reference agents (cimetidine: 10, 100, 500 mg x mL(-1); ranitidine: 2.5, 25, 250 mg x mL(-1); famotidine: 10, 50, 100 mg x mL(-1); omeprazole: 10, 50, 100 mg x mL(-1); sucralfate: 1, 5, 10 mg x mL(-1) were implanted subcutaneously in the lumbar region. The sponges were removed after 3 or 7 d, fixed in formalin, and processed for histologic and histochemical evaluation and morphometry assessment. Compared with the control values, the number of newly formed endothelial spaces inside newly formed granulation tissue was markedly increased in all animals treated with BPC 157, cimetidine, ranitidine, famotidine, sucralfate and omeprazole, a consistent finding noted after either 3 or 7 d. Compared with control values, markedly more granulation tissue was noted in the rats in the groups of animals treated with BPC 157 (50 microg) and in the rats treated with sucralfate in all dosages used, euthanized after 3 d. In all groups treated with H2-blockers however, similar values to those of controls were noted. Thus, it could be concluded that an evident angiogenic property was consistently noted for the novel pentadecapeptide BPC 157, H2-blockers (cimetidine, famotidine and ranitidine) and omeprazole, besides the well known angiogenic effect of sucralfate. Furthermore, unlike H2-blockers and omeprazole, BPC 157 stimulates the formation of granulation tissue, suggesting a particular activity, similar to that previously noted for sucralfate.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10672992&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Selection of patients for successful maintenance treatment of esophagitis with low-dose omeprazole: use of 24-hour gastric pH monitoring.

Ladas SD, Tassios PS, Raptis SA.

Second Department of Internal Medicine, Evangelismos Hospital, Athens University, Greece.

OBJECTIVE: Treating patients with erosive esophagitis and maintaining remission in a cost-effective fashion is a desirable goal in clinical practice. There are no established criteria to identify patients with healed esophagitis who will subsequently remain in remission with low-dose omeprazole therapy. We investigated whether 24-h esophageal-gastric pH monitoring could provide criteria to select patients for low-dose omeprazole maintenance therapy. METHODS: Seventy consecutive symptomatic outpatients with grade 2-3 reflux esophagitis were prospectively investigated. They were treated with 20 mg/day omeprazole for 2 months. Those with healed esophagitis were given alternate-evening 20-mg omeprazole maintenance therapy for 6 months. Clinical evaluation, endoscopy, and 24-h esophageal-gastric pH were done at the end of each treatment period. Results of pH studies of patients in remission were compared with those with endoscopically documented relapse of esophagitis. RESULTS: In 63/70 patient (intention-to-treat, 90%; 95% confidence interval [CI], 83-97%) esophagitis was healed at 2 months. During the 6-month maintenance period esophagitis remain healed in 28 (G1) (40%; 95% CI, 29-52%), but recurred in 32 patients (G2). During healing with omeprazole 20 mg/day the 24-h gastric pH was below 4 for <10% of the time in 96% of the patients, who subsequently remained in long-term remission with low-dose maintenance therapy (G1), but not in any patient with recurrence of esophagitis (G2). The 10% threshold value has a specificity of 1.00 and sensitivity of 0.96. CONCLUSIONS: The 24-h intragastric pH monitoring during 20 mg/day omeprazole therapy provides criteria by which to preselect patients with reflux esophagitis who will remain in remission with low-dose omeprazole therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10685738&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effects of intramuscular omeprazole on gastric acid secretion in horses over a twenty-four hour period.

Sandin A, Andrews FM, Nadeau JA, Doherty TJ, Nilsson G.

Department of Animal Physiology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.

The effect of intramuscular (i.m.) omeprazole (0.25 or 1.0 mg/kg bwt; LD and HD), respectively, on volume, total acid output (TAO) and pH of the gastric juice was studied during 24 h in 5 horses with a chronically implanted gastric cannula. Whether secretion in controls was basal or stimulated with pentagastrin (8 micrograms/kg bwt/h), volume (NS) and TAO (P < 0.01, NS) gradually decreased and pH increased (P < 0.05, NS). Omeprazole significantly reduced the average basal TAO by 49 +/- 6% (LD) and 88 +/- 3% (HD) and the stimulated TAO by 64 +/- 2% and 97 +/- 1%. Basal pH in controls was 2.1-4.2 and after omeprazole treatment, pH 2.8-4.1 (LD) and 2.4-6.6 (HD). After stimulation, the corresponding pH values were 2.6-3.3, 3.9-4.9 and 5.4-7.2. The biological availability of omeprazole was 70-80%. Due to the simplicity of the administration technique and the higher biological availability, intramuscular administration may offer a practical and less expensive way of treating gastric ulcers in horses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10696294&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Comparison of the antisecretory effects of omeprazole when administered intravenously, as acid-stable granules and as an oral paste in horses.

Haven ML, Dave K, Burrow JA, Merritt AM, Harris D, Zhang D, Hickey GJ.

Department of Animal Health, Merck Research Laboratories, Rahway, New Jersey 07065, USA.

The antisecretory activity of omeprazole on gastric acid when administered i.v., intragastrically or per os, was evaluated in 2 female and 3 castrated male horses. Each horse had been prepared with a chronic indwelling gastric cannula. A single i.v. administration of omeprazole (1.5 mg/kg bwt) was effective in abolishing basal and pentagastrin (PG)-stimulated acid secretion. Once daily, nasogastric administration of omeprazole in acid-stable granules for 5 days inhibited acid secretion in a dose-dependent manner: 57% (1.5 mg/kg bwt) and 98% (5.0 mg/kg bwt) reduction of PG-stimulated acid secretion. The degree of inhibition was maintained over a 19 day treatment period with once daily dosing. A prototype oral paste formulation containing either acid-stable omeprazole granules or uncoated omeprazole powder was equipotent when compared to a similar dosage of acid-stable omeprazole granules administered by nasogastric tube. A dose-dependent inhibition was seen with the oral paste formulation containing omeprazole powder: 55% (1.5 mg/kg bwt) and 77% (3.0 mg/kg bwt) reduction of PG-stimulated acid secretion after 5 days. Therefore, a paste formulation of omeprazole powder may offer an effective, easily administered, once daily acid inhibitory treatment for gastric ulcer disease in horses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10696295&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Comparison of derivative spectrophotometric and liquid chromatographic methods for the determination of omeprazole in aqueous solutions during stability studies.

Castro D, Moreno MA, Torrado S, Lastres JL.

Dpto. Farmacia y Tecnologia Farmaceutica, Facultad de Farmacia, Universidad Complutense de Madrid, Spain. marco eucmax.sim.ucm.es

A first derivative spectrophotometric method was developed for the determination of omeprazole in aqueous solutions during stability studies. The derivative procedure was based on the linear relationship between the omeprazole concentration and the first derivative amplitude at 313 nm. The first derivative spectra was developed between 200 and 400 nm (deltalambda = 8). This method was validated and compared with the official high-performance liquid chromatography (HPLC) method of the USP. It showed good linearity in the range of concentrations studied (10-30 microg ml(-1)), precision (repeatability and inter-day reproducibility), recovery and specificity in stability studies. It also seemed to be 2.59 times more sensitive than the HPLC method. These results allowed to consider this procedure as useful for the rapid analysis of omeprazole in stability studies since there was no interference with its decomposition products.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10703983&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Validation of an automated liquid chromatographic method for omeprazole in human plasma using on-line solid-phase extraction.

Garcia-Encina G, Farran R, Puig S, Martinez L.

Laboratorios Dr. Esteve, S.A., Barcelona, Spain. ggarcia esteve.es

An automated system using on-line solid-phase extraction and HPLC with UV detection has been validated in order to determine omeprazole in human plasma. The extraction was carried out using C18 cartridges. After washing, omeprazole was eluted from the cartridge with mobile phase onto an Inertsil ODS-2 column. The developed method was selective and linear for drug concentrations ranging between 5 and 500 ng ml(-1). The recovery of omeprazole ranged from 88.1 to 101.5%, and the limit of quantitation (LOQ) was 5 ng ml(-1). The intraday accuracy ranged from 93.1 to 106.2% and the interday accuracy varied from 95.4 to 105.1%. For the LOQ, good values of precision (8.7 and 17.5% for intraday and interday, respectively) were also obtained. This automated system has been applied to determine omeprazole in human plasma samples from bioequivalence studies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10703993&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
The gastric H,K-ATPase blocker lansoprazole is an inhibitor of chloride channels.

Schmarda A, Dinkhauser P, Gschwentner M, Ritter M, Furst J, Scandella E, Woll E, Laich A, Rossmann H, Seidler U, Lang F, Paulmichl M.

Department of Physiology, University of Innsbruck, Austria.

1. It was postulated that swelling dependent chloride channels are involved in the proton secretion of parietal cells. Since omeprazole, lansoprazole and its acid activated sulphenamide form AG2000 are structurally related to phenol derivatives known to block swelling dependent chloride channels, we set out to test, whether these substances--which are known to block the H,K-ATPase--could also lead to an inhibition of swelling-dependent chloride channels. Swelling-dependent chloride channels--characterized in many different cell types--show highly conserved biophysical and pharmacological features, therefore we investigated the effect of omeprazole, lansoprazole and its acid activated sulphenamide form AG2000 on swelling-dependent chloride channels elicited in fibroblasts, after the reduction of the extracellular osmolarity. 2. Omeprazole, lansoprazole and its acid activated sulphenamide form AG2000 are able to block swelling-dependent chloride channels (IClswell). 3. Lansoprazole and its protonated metabolite AG2000 act on at least two different sites of the IClswell protein: on an extracellular site which seems to be in a functional proximity to the nucleotide binding site, and on an intracellular site which allows the formation of disulfide-bridges. 4. The inhibition of the proton pump and the simultaneous blocking of chloride channels by omeprazole, lansoprazole and its acid activated sulphenamide form AG2000, as described here could be an effective mode to restrict proton secretion in parietal cells.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10711360&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Long-term omeprazole treatment in resistant gastroesophageal reflux disease: efficacy, safety, and influence on gastric mucosa.

Klinkenberg-Knol EC, Nelis F, Dent J, Snel P, Mitchell B, Prichard P, Lloyd D, Havu N, Frame MH, Roman J, Walan A, Group LT.

Department of Gastroenterology, Free University Hospital, Amsterdam, The Netherlands. EC.Klinkenberg azvu.nl

BACKGROUND & AIMS: The efficacy and safety of long-term acid suppression remains a subject for debate. We report data from patients with refractory reflux esophagitis who were undergoing maintenance therapy with >/=20 mg omeprazole daily for a mean period of 6.5 years (range, 1.4-11.2 years). METHODS: Patients with severe reflux esophagitis resistant to long-term therapy with H(2)-receptor antagonists and who were not eligible for surgery were evaluated at least annually for endoscopic relapse and histological changes in the gastric corpus. RESULTS: In 230 patients (mean age, 63 years at entry; 36% were >/=70 years), there were 158 relapses of esophagitis during 1490 treatment years (1 per 9.4 years), with no significant difference in relapse rates between Helicobacter pylori-positive and -negative patients. All patients rehealed during continued therapy with omeprazole at the same or higher dose. The annual incidence of gastric corpus mucosal atrophy was 4.7% and 0.7% in H. pylori-positive and -negative patients, respectively, which was mainly observed in elderly patients who had moderate/severe gastritis at entry. In patients with baseline moderate/severe gastritis, the incidences were similar: 7.9% and 8.4%, respectively. Corpus intestinal metaplasia was rare, and no dysplasia or neoplasms were observed. The adverse event profile was as might be expected from this elderly group of patients. CONCLUSIONS: Long-term omeprazole therapy (up to 11 years) is highly effective and safe for control of reflux esophagitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10734017&dopt=Abstract omeprozole Prilosec