omeprazole, Prilosec
Intragastric volatile N-nitrosamines, nitrite, pH, and Helicobacter pylori during long-term treatment with omeprazole.

Vermeer IT, Engels LG, Pachen DM, Dallinga JW, Kleinjans JC, van Maanen JM.

Department of Health Risk Analysis and Toxicology, Maastricht University, Maastricht, The Netherlands. Ingrid.Vermeer numico-research.nl

BACKGROUND & AIMS: This study evaluated the effect of long-term gastric acid suppressive therapy with omeprazole on intragastric levels of carcinogenic N-nitrosamines and related parameters. METHODS: Forty-five patients on long-term omeprazole medication (mean, 35 months) and 13 healthy subjects without medication participated. Volatile N-nitrosamines were determined in gastric juice and urine. Intragastric pH, nitrite, nitrate, and H. pylori status were determined. DNA isolated from gastric biopsy specimens was analyzed for precarcinogenic alkyl-DNA adducts. RESULTS: The intragastric pH in patients was significantly higher compared with controls (P = 0.0001). Gastric nitrite levels in patients were nonsignificantly higher. There was no difference in total levels of intragastric volatile N-nitrosamines between patients and controls, however, urinary N-nitrosodimethylamine excretion was higher in patients (P = 0.001). On omeprazole, Helicobacter pylori-positive vs. -negative patients had a nonsignificantly higher intragastric nitrite level and higher urinary N-nitrosodimethylamine excretion. No alkyl-DNA adducts could be detected in gastric epithelium. CONCLUSIONS: Increased intragastric pH caused by long-term treatment with omeprazole does not result in increased intragastric levels of nitrite and volatile N-nitrosamines. The significantly higher urinary N-nitrosamine excretion implies the risk of increased endogenous formation of N-nitrosamines during long-term omeprazole treatment. This risk may be higher in H. pylori-positive patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11522734&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Fexofenadine does not affect omeprazole pharmacokinetics: both are putative P-glycoprotein substrates.

Takahata T, Yasui-Furukori N, Yoshiya G, Uno T, Sugawara K, Tateishi T.

Department of Clinical Pharmacology, Hirosaki University School of Medicine, Hirosaki, Japan.

An in vitro study has recently suggested that a proton pump inhibitor, omeprazole, is a modest substrate of P-glycoprotein. Several studies have shown P-glycoprotein is involved in the absorption and excretion of fexofenadine. Therefore, we examined the effect of fexofenadine on the pharmacokinetics of omeprazole. Eight healthy volunteers participated in this study. They received a single oral dose of 40 mg omeprazole before and after 60 mg fexofenadine (10 doses over 6 days). Blood samplings were performed up to 8 hr after each dosing. Plasma concentrations of omeprazole and its two metabolites were quantified with high-performance liquid chromatography. In addition, the effect of fexofenadine on P-glycoprotein function was examined by flow cytometry using rhodamine 123 and CD56-positive lymphocytes. Comparison of the pharmacokinetic parameters of omeprazole before and after fexofenadine revealed that there were no differences in peak concentration, time to peak concentration, area under the time concentration curve up to 8 hr, and elimination half-life. There were also no differences in these pharmacokinetic parameters for the two metabolites of omeprazole. Flow cytometric analysis revealed that fexofenadine did not inhibit the efflux of rhodamine 123. This study indicated that there was probably no drug interaction between omeprazole and fexofenadine, which might be due to less contribution of P-glycoprotein to omeprazole absorption, insufficient inhibitory effect of fexofenadine on P-glycoprotein, or the involvement of other transporters such as organic anion transporting polypeptides.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15125696&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Long-term omeprazole treatment suppresses body weight gain and bone mineralization in young male rats.

Cui GL, Syversen U, Zhao CM, Chen D, Waldum HL.

Dept. of Physiology and Biomedical Engineering, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim.

BACKGROUND: The stomach is rich in endocrine cells, including those producing ghrelin, which is thought to play a role in the control of body growth. Omeprazole treatment is associated with hypergastrinaemia, resulting in growth of the oxyntic mucosa in general and the enterochromaffin-like (ECL) cells in particular. In the present study, we examined the effects of long-term omeprazole treatment on young male rats with respect to body growth and stomach. METHODS: Male rats (24 days old) were treated with omeprazole (400 micromol/kg/day) or vehicle for 77 days. The body weight was recorded twice per week. At sacrifice, dual-energy X-ray absorptiometry (DXA) was used to assess total bone area, bone mineral content (BMC), bone mineral density (BMD) and body composition (fat and lean body mass). The lengths of the spine and the femur were recorded. The plasma concentrations of gastrin and histamine were determined by radioimmunoassays. The endocrine cells of the stomach were examined by immunocytochemistry. RESULTS: The body weight gain was suppressed by omeprazole treatment. The bone area, BMC and BMD were reduced, while the lengths of the spine and the femur and the body composition were unchanged. Omeprazole-induced hypergastrinaemia was associated with enlargement of the oxyntic area and with hyperplasia of ECL cells but not of A-like cells and D cells. In contrast, the enterchromaffin (EC) cell density in the antrum was reduced. CONCLUSIONS: Omeprazole treatment of young male rats reduces body weight and bone mass gain. The densities of ECL cells in the oxyntic mucosa was increased and of the EC cells in the antral mucosa reduced.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11589371&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Pharmacokinetics of omeprazole in patients with liver cirrhosis and extrahepatic portal venous obstruction.

Kumar R, Chawla YK, Garg SK, Dixit RK, Satapathy SK, Dhiman RK, Bhargava VK.

Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India 160-012. medinst pgi.chd.nic.in

Omeprazole is frequently used in patients with cirrhosis of the liver to treat peptic ulcer disease. It is also used for the healing of mucosal lesions after endoscopic sclerotherapy of esophageal varices in cirrhosis and extraheptic portal vein obstruction (EHPVO). This study was carried out with the aim of determining the pharmacokinetics of omeprazole in different degrees of liver cirrhosis and in patients with EHPVO, compared with healthy volunteers. Ten healthy volunteers, 30 patients with cirrhosis of the liver, divided into 3 groups of 10 depending on severity (according to Child-Pugh classification A, B and C) and ten patients with EHPVO participated in the study. The subjects received an omeprazole 20 mg capsule after an overnight fast. Blood samples were collected at 0, 0.5, 1, 1.5, 2, 2.5, 3, 6, 9 and 24 h after drug administration. Omeprazole level in plasma was estimated by reverse-phase high performance liquid chromatography (HPLC). The elimination half-life was significantly (p < 0.05) increased to 2.38 +/- 0.16, 3.26 +/- 0,12, 3.58 +/- 0.31 and 2.59 +/- 0.22 h in patients with different grades of cirrhosis (A, B and C) and also in patients with EHPVO, respectively, compared with 1.054 + 0.10 h in healthy volunteers. A similar significant increase (p < 0.05) was observed in the AUC(0alpha), while C(max) was significantly increased to 400.40 +/- 27.89 and 602 +/- 55.13 ng/ml in only grade C cirrhosis patients and EHPVO patients, compared with 303.5 +/- 36.42 ng/ml in healthy volunteers. No significant difference was observed in T(max). It was concluded that the metabolism of omeprazole was significantly impaired in both liver cirrhosis and EHPVO in comparison with healthy volunteers. (c) 2003 Prous Science. All rights reserved.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14671680&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Lung lesions and anti-ulcer agents beneficial effect: anti-ulcer agents pentadecapeptide BPC 157, ranitidine, omeprazole and atropine ameliorate lung lesion in rats.

Stancic-Rokotov D, Slobodnjak Z, Aralica J, Aralica G, Perovic D, Staresinic M, Gjurasin M, Anic T, Zoricic I, Buljat G, Prkacin I, Sikiric P, Seiwerth S, Rucman R, Petek M, Turkovic B, Kokic N, Jagic V, Boban-Blagaic A.

Clinic for Thoracic Surgery Jordanovac, Medical Faculty University of Zagreb, Zagreb, Croatia.

Anti-ulcer agents may likely attenuate lesions outside the gastrointestinal tract, since they had protected gastrectomized rats (a "direct cytoprotective effect"). Therefore, their therapeutic potential in lung/stomach lesions were shown. Rats received an intratracheal (i.t.) HCl instillation [1.5 ml/kg HCl (pH 1.75)] (lung lesion), and an intragastric (i.g.) instillation of 96% ethanol (gastric lesion; 1 ml/rat, 24 h after i.t. HCl instillation), then sacrificed 1 h after ethanol. Basically, in lung-injured rats, the subsequent ethanol-gastric lesion was markedly aggravated. This aggravation, however, in turn, did not affect the severity of the lung lesions in the further period, at least for 1 h of observation. Taking intratracheal HCl-instillation as time 0, a gastric pentadecapeptide, GEPPPGKPADDAGLV, M.W.1419, coded BPC 157 (10 microg, 10 ng, 10 pg), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg), were given [/kg, intraperitoneally (i.p.)] (i) once, only prophylactically [as a pre-treatment (at -1h)], or as a co-treatment [at 0)], or only therapeutically (at +18h or +24 h); (ii) repeatedly, combining prophylactic/therapeutic regimens [(-1 h)+(+24 h)] or [(0)+(+24 h)], or therapeutic/therapeutic regimens [(+18 h)+(+24 h)]. For all agents, combining their prophylactic and salutary regimens (at -1 h/+24 h, or at 0/+24 h) attenuated lung lesions; even if effect had been not seen already with a single application, it became prominent after repeated treatment. In single application studies, relative to controls, a co-treatment (except to omeprazole), a pre-treatment (at -1 h) (pentadecapeptide BPC 157 and atropine, but not ranitidine and omeprazole) regularly attenuated, while therapeutically, atropine (at +18 h), pentadecapeptide BPC 157 highest dose and omeprazole (at +24 h), reversed the otherwise more severe lung lesions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11595454&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Early laparoscopic Nissen fundoplication for recurrent reflux esophagitis: a cost-effective alternative to omeprazole.

Nessen SC, Holcomb J, Tonkinson B, Hetz SP, Schreiber MA.

Department of Surgery, General Surgery Service, William Beaumont Army Medical Center, El Paso, TX 79920, USA.

BACKGROUND: Eighty percent of patients treated medically for gastroesophageal reflux disease relapse after treatment. Many of these patients require indefinite treatment with omeprazole to prevent recurrence. Nissen fundoplication has been shown to be effective, safe and cost effective in the management of gastroesophageal reflux disease. We suggest a treatment algorithm, which encourages early surgical intervention in cases of recurrent esophagitis after a previously successful two-month course of omeprazole. METHODS: We have offered laparoscopic Nissen fundoplication since 1993. Patients who received Nissen fundoplication since 1990 were asked to report return to baseline activity, medications, and lifestyle changes. Concurrent chart review of patients treated with omeprazole was conducted to analyze cost. RESULTS: Patients receiving laparoscopic Nissen fundoplication were discharged significantly sooner and spent significantly less time convalescing when compared to those who underwent open Nissen fundoplication. Laparoscopic Nissen fundoplication became cost effective at 1.5 to 2 years when compared to omeprazole. CONCLUSION: Based on cost analysis, patient satisfaction, acceptable complication rate, and efficient use of time and resources, we recommend laparoscopic Nissen fundoplication as the appropriate treatment in patients who develop recurrent esophagitis after a two-month treatment with omeprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10444007&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Signal transduction-mediated CYP1A1 induction by omeprazole in human HepG2 cells.

Kikuchi H, Hossain A.

Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.

Benzimidazole compounds, such as omeprazole and thiabendazole, are a different type of CYP1A1-inducer from Ah receptor-ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3-methylcholanthrene. In HepG2 cells, the commonly used tyrosine kinase-inhibitors, herbimycin-A and a series of tyrphostins, inhibited the induction of CYP1A1 produced by treatment with TCDD. Genistein, another type of tyrosine kinase inhibitor, inhibited the induction of CYP 1A1 whether it was produced by omeprazole or TCDD; however, this inhibition was caused by a dual effect of genistein, that is an anti-tyrosine kinase and an anti-topoisomerase I effect. An antagonist of Ah receptor, 3'-methoxy-4'-aminoflavone (1 microM), did not inhibit the induction of CYP1A1 produced in HepG2 cells by omeprazole or alpha-naphthoflavone (50 microM), but this antagonist did inhibit that produced by TCDD. Thus, omeprazole appears to induce CYP1A1 by initiating a protein tyrosine kinase-mediated signal transduction pathway, a different pathway from that initiated by TCDD.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10445394&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effects of orally administered enteric-coated omeprazole on gastric acid secretion in horses.

Andrews FM, Doherty TJ, Blackford JT, Nadeau JA, Saxton AM.

Department of Large Animal Clinical Sciences, University of Tennessee, Knoxville 37901-1071, USA.

OBJECTIVES: To determine the effects of orally administered omeprazole, as enteric-coated capsules, on baseline and stimulated gastric acid secretion in horses. ANIMALS: 5 healthy 8-year-old mixed-breed horses fitted with gastric cannulas. PROCEDURE: Enteric-coated granules of omeprazole were mixed with corn syrup and administered orally once daily for 5 consecutive days. On days 1 and 5 beginning 5 hours after omeprazole administration, 4 gastric fluid samples were collected, each for 15 minutes, via the gastric cannula (baseline samples). Pentagastrin was administered IV as a constant infusion for the subsequent 2 hours, and 15-minute gastric fluid samples were again collected (stimulated samples). Fluid volume, acidity (mmol H-/L), and pH and gastric acid production (mmol H+) were determined for all baseline samples and for stimulated samples collected during the second hour of pentagastrin infusion. Control experiments were done in a similar manner after giving corn syrup alone to the same horses. RESULTS: Compared with values obtained during control experiments, baseline and stimulated gastric fluid acidity and gastric acid production significantly decreased, and the mean pH of gastric fluid samples significantly increased, after horses were given 5 daily doses of omeprazole. CONCLUSIONS AND CLINICAL RELEVANCE: Enteric-coated omeprazole (1.0 mg/kg of body weight; PO) administered once daily for 5 days significantly inhibited unstimulated and pentagastrin-stimulated gastric acid secretion in horses. This commercially available formulation of omeprazole may be efficacious in the treatment of gastroduodenal ulcers in horses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10451198&dopt=Abstract omeprozole Prilosec