omeprazole, Prilosec
Risk factors for esophageal candidiasis.

Chocarro Martinez A, Galindo Tobal F, Ruiz-Irastorza G, Gonzalez Lopez A, Alvarez Navia F, Ochoa Sangrador C, Martin Arribas MI.

Department of Internal Medicine, Hospital Virgen de la Concha, Zamora, Spain. achocarrom medynet.com

The role of gastric acid inhibitors as predisposing factors for Candida esophagitis is unknown. A retrospective case-control study of esophageal candidiasis was conducted in human immunodeficiency virus (HIV)-negative patients diagnosed from January 1991 to December 1997. The diagnosis of esophageal candidiasis was always made on the basis of endoscopic and histological criteria. Fifty-one patients were diagnosed with esophageal candidiasis, 15 of whom had esophageal complaints and 48 of whom suffered from another previous chronic disease (17 had cancer). In addition, 20 patients had previously been treated with antibiotics, 13 with steroids and 14 with omeprazole. In the multivariate analysis, neoplasm (odds ratio, 5.50; 95% confidence interval, 1.94-15.56) and therapy with antibiotics (odds ratio, 11.97; 95% confidence interval, 3.82-37.45), steroids (odds ratio, 35.52; 95% confidence interval, 3.90-324.01) or omeprazole (odds ratio, 18.23; 95% confidence interval, 4.67-71.03) were all associated with esophageal candidiasis. These data suggest that Candida esophagitis tends to occur in patients with chronic diseases, most of whom have been previously treated with antibiotics, steroids or omeprazole. The findings support the hypothesis that treatment with omeprazole favors the development of esophageal candidiasis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10746494&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Acid secretion and response to pentagastrin or omeprazole in human fetal stomach xenografts.

Muhale F, Morali A, Duprez A, Lozniewski A, Angioi K.

Laboratoire de Microchirurgie Experimentale, Faculte de Medecine de Nancy, Vandoeuvre-les-Nancy, France.

BACKGROUND: The dual capacity of stomach tissue to secrete acid and to respond to secretagogues is indicative of the terminal stages of gastric functional maturation. In this study 6- to 10-week-old human fetal stomachs xenografted into nude mice were used to study parietal cells' functional maturation. METHODS: Thirty-four transplants were microsurgically grafted either inside a pouch created on the nude peritoneum (n = 15) or on the host stomach and esophagus (n = 19). The mucosa of transplanted tissues was analyzed by immunohistochemical techniques to detect gastric cells. Gastric cell secretions were collected before and after pentagastrin or omeprazole treatment. RESULTS: Parietal, G, and D cells were detected immunohistochemically only after 1 month of grafting. All xenografts actively secreted acid after 1 or 2 months' transplantation at each graft site. Acid secretion was significantly stimulated by intraperitoneally injected pentagastrin (mean pH +/- SD, 3.2 +/- 0.7 vs. 2.0 +/- 0.5; n = 10, P = 0.005) and was dramatically inhibited by intragastrically administered omeprazole (2.3 +/- 0.6 vs. 6.5 +/- 0.7; n = 15, P = 0.0007) after 5 hours. CONCLUSION: Stomach xenografts were able to develop normally. Parietal cells were physiologically mature with functional proton pumps and active gastrin receptors, as demonstrated after omeprazole and pentagastrin treatment, respectively. Because stomach xenografts matured very rapidly, it is possible that a stomach xenograft model can be used for further studies on the functional maturation of human gastric epithelial cells, as well as the factors that influence this maturation in humans.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10749406&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Prevention and healing of experimental indomethacin-induced gastric lesions: effects of ebrotidine, omeprazole and ranitidine.

Arroyo MT, Lanas A, Sainz R.

Services of Gastroenterology and Research Unit (UMI), Hospital Clinico Universitario, University of Zaragoza, Spain.

BACKGROUND: Ebrotidine is a new H2 receptor antagonist that potentiates the gastric mucosal barrier. AIM: To compare ebrotidine with other anti-secretory drugs in the prevention and healing of indomethacin-induced gastric lesions. METHODS: Three different models of indomethacin-induced gastric lesions were used. (1) Fasted rat model: indomethacin was intra-gastrically administered in rats pre-treated with different doses of the anti-secretory drugs. (2) Re-fed rat model: rats orally treated with different doses of anti-secretory drugs had free access to chow pellets and were then treated with parenteral indomethacin. (3) Healing model: either oral or parenteral anti-secretory drugs were given after indomethacin administration. Computer-assisted analysis of the area of damage was expressed as ulcer index. Gastric secretion was evaluated in the pylorus-ligated rat model. RESULTS: Inhibition of acid secretion was in the order omeprazole > ebrotidine = ranitidine. Ebrotidine at the highest dose used (100 mg/kg) and omeprazole, but not ranitidine, significantly prevented indomethacin-induced corpus (fasted rat) and antrum (re-fed rat) gastric lesions. In the ulcer healing model, oral administration of omeprazole and both ranitidine and ebrotidine at the highest dose used improved the ulcer index. The parenteral administration of these drugs had a lesser effect than the oral route and was in the order ebrotidine > omeprazole > ranitidine. CONCLUSIONS: Ebrotidine is effective in both the prevention and healing of indomethacin-induced experimental gastric lesions. In these models, the effect of ebrotidine is comparable to omeprazole and more effective than ranitidine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10750652&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
The omeprazole test is as sensitive as 24-h oesophageal pH monitoring in diagnosing gastro-oesophageal reflux disease in symptomatic patients with erosive oesophagitis.

Fass R, Ofman JJ, Sampliner RE, Camargo L, Wendel C, Fennerty MB.

Section of Gastroenterology, Tucson VA Medical Center and Arizona Health Sciences Center, 85723, USA.Ronnie.Fass Med.Va.gov

BACKGROUND: Ambulatory 24-h oesophageal pH monitoring and a short course of high dose omeprazole can be used as diagnostic modalities for GERD. However, comparative studies of the diagnostic accuracy and reliability of both strategies have not been performed. AIM: To compare the omeprazole test to ambulatory 24-h oesophageal pH monitoring in diagnosing GERD in symptomatic patients using endoscopically proven erosive oesophagitis as a gold standard. METHODS: Patients with heartburn underwent an upper endoscopy. Only those with erosive oesophagitis were included in the study. Subsequently, patients underwent ambulatory 24-h oesophageal pH monitoring and an 'omeprazole test.' Daily symptoms were recorded during the first week (baseline) and repeated during the second week on therapy (omeprazole 40 mg in the morning and 20 mg in the evening). RESULTS: Thirty-five patients were included in the study. The omeprazole test was significantly more sensitive in diagnosing GERD than total acid contact time on 24-h oesophageal pH monitoring (83% vs. 60%; P < 0.03). However, the sensitivity of the pH test increased to 80% after adding patients with a positive symptom index, and patients with abnormal acid exposure in the supine or erect positions despite normal total acid contact time. Patients with a normal pH test were significantly younger (49 +/- 2.6 years) than those with abnormal test (59 +/- 1.8; P=0.002). CONCLUSIONS: In this study an omeprazole test was at least as sensitive as ambulatory 24-h oesophageal pH monitoring in diagnosing GERD in patients with erosive oesophagitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10759617&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Clinical and fiscal impact of lansoprazole intolerance in veterans with gastro-oesophageal reflux disease.

Gerson LB, Hatton BN, Ryono R, Jones W, Pulliam G, Sampliner RE, Triadafilopoulos G, Fass R.

Department of Gastroenterology, Stanford University School of Medicine and VA Palo Alto Health Care System, CA 94304, USA. Igerson leland.stanford.edu

BACKGROUND: Omeprazole was replaced by lansoprazole as the only proton pump inhibitor on the Veterans Affairs (VA) formulary in February 1997. We aimed to assess the clinical and fiscal impact of this conversion at two VA hospitals. METHODS: We identified lansoprazole intolerant patients using pharmacy databases. We reviewed medical records to obtain data regarding reasons for lansoprazole intolerance. The costs of the formulary change and the savings to the VA were calculated. RESULTS: A total of 3833 patients required long-term proton pump inhibitor therapy; 2224 (58%) were started on lansoprazole and 1479 (39%) were converted from omeprazole to lansoprazole. The remaining 130 (3.4%) patients were never converted from omeprazole to lansoprazole. Of the 3833 patients, 325 (8.5%) currently receive omeprazole therapy; of these, 195 out of 3703 (5.3%) patients are true lansoprazole failures; 172 of these 195 patients completed the study. Most (87%) of the lansoprazole intolerant patients received prior omeprazole. Discontinuation of lansoprazole was due to poor symptom control in 69% and/or side-effects (22%) including diarrhoea (10%), abdominal pain (5%), or hives (1%). The 1-year cost of managing lansoprazole failure in 195 patients was $61 690. However, the savings to the VA during the same time period, which totalled $321 360, more than offset the costs associated with the conversion. CONCLUSIONS: Lansoprazole intolerance requiring omeprazole conversion occurred in 5% of veterans on proton pump inhibitor therapy for chronic gastro-oesophageal reflux disease (GERD) symptoms and in 10% of patients with prior omeprazole success. The VA realized substantial cost savings in association with the formulary change.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10759618&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
The effect of ammonia on omeprazole-induced reduction of gastric acidity in subjects with Helicobacter pylori infection.

Bercik P, Verdu EF, Armstrong D, Idstrom JP, Cederberg C, Markert M, Crabtree JE, Stolte M, Blum AL.

Division of Gastroenterology, CHUV, Lausanne, Switzerland.

OBJECTIVE: Omeprazole produces a higher intragastric pH during Helicobacter pylori (H. pylori) infection than after cure. We tested the hypothesis that this difference is due to the production of ammonia by H. pylori. METHODS: Gastric acidity and acid output (AO) were measured overnight in 12 subjects, with and without omeprazole, before and 1 and 6 months after cure of H. pylori infection. Gastric ammonia ([NH3]), total bile acid ([TBA]) and protein concentrations and plasma omeprazole levels were measured. RESULTS: During omeprazole, median AO were 0.0 mmol/h before, 0.86 mmol/h (p = 0.003 vs before cure) at 1 month, and 0.34 mmol/h (p = 0.02) at 6 months after cure; median NH3 output was 0.17 mmol/h before, 0.03 mmol/h (p = 0.002) at 1 month, and 0.02 mmol/h (p = 0.005) at 6 months after cure. AO and NH3 output were similar 1 and 6 months after cure. When corrected for [NH3], AO and gastric pH curves were similar before and after cure. Omeprazole plasma levels increased after cure and gastric [TBA] were unchanged. CONCLUSIONS: The higher pH observed before cure of H. pylori during omeprazole administration is attributable, in large part, to ammonia production. Other acid-neutralizing substances and changes in acid secretion may also be important, but duodenogastric reflux and omeprazole pharmacokinetics are not involved.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10763943&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
H2-blocker modulates heart rate variability.

Ooie T, Saikawa T, Hara M, Ono H, Seike M, Sakata T.

First Department of Internal Medicine, School of Medicine, Oita Medical University, Hasamamachi, Japan.

The use of H2-blockers in the treatment of patients with peptic ulcer has become popular. However, this treatment has adverse cardiovascular effects. The aim of this study was to investigate proarrhythmic rhythm and autonomic nervous activity by analyzing heart rate variability in patients treated with omeprazole, ranitidine, and plaunotol. Nineteen patients (mean age 67.5 +/- 2.7 years) with active gastric ulcer were treated with omeprazole (20 mg/day) for 8 weeks, then ranitidine (300 mg/day) for the next 4 months, and finally plaunotol (240 mg/day). At each stage of the treatment, Holter electrocardiography was performed, and heart rate variability and arrhythmias analyzed. Heart rate variability yielded power in the low- (0.04-0.15 Hz) and high-frequency components (0.15-0.4 Hz). Although both ranitidine and omeprazole induced little change in cardiac rhythm, the high-frequency power was higher (10.3 +/- 0.8 vs 8.6 +/- 0.6 ms, P < 0.05) and the ratio of low-to-high frequency power was lower (1.41 +/-0.10 vs 1.59 +/- 0.09. P < 0.05) during ranitidine than during plaunotol treatment. Cosinor analysis of heart rate variability revealed a decreased amplitude of low-frequency power during omeprazole compared with during ranitidine and plaunotol treatment. Ranitidine modulated high-frequency power which may be related to the adverse cardiovascular effects of H2-blocker.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10776806&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Affinities at the verapamil binding site of MDR1-encoded P-glycoprotein: drugs and analogs, stereoisomers and metabolites.

Neuhoff S, Langguth P, Dressler C, Andersson TB, Regardh CG, Spahn-Langguth H.

School of Pharmacy, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany.

OBJECTIVES: The multidrug transporter P-glycoprotein (P-gp) appears to play a significant role in drug absorption and disposition. Hence, it is of interest to evaluate structure-affinity relationships for the purpose of making predictions. METHODS: The affinity to P-gp of related molecular structures from various groups of drugs was determined using competitive radioligand-binding assays. Structural analogs, stereoisomers and metabolites of verapamil-type calcium antagonists, beta-adrenoceptor antagonists as well as omeprazole, omeprazole enantiomers and the sulfone metabolite of omeprazole were investigated. RESULTS: Whereas some stereoselectivity was detected for the high-affinity P-gp substrates verapamil and carvedilol, little or no differences were observed in the case of other beta-blockers. One of the 4 labetalol stereoisomers, the R,R-isomer dilevalol, had an IC50 value half that of labetalol. CONCLUSIONS: Metabolites of verapamil, gallopamil, carvedilol and omeprazole are characterized by having higher IC50 values (lower P-gp affinity) than the respective parent compounds. Only the acebutolol metabolite, diacetolol, had a P-gp affinity comparable to that of the parent compound.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10783826&dopt=Abstract omeprozole Prilosec