Disease relevance of Ebrotidine

• Rapid progression to liver cirrhosis of toxic hepatitis due to ebrotidine [1].
• Ebrotidine is a new H2-receptor antagonist that, in addition to its antisecretory activity, exhibits a remarkable ability for gastric mucosal protection and acts as a potent inhibitor of protease and lipase enzymes elaborated by Helicobacter pylori [2].
• RESULTS: Ebrotidine achieved a duodenal ulcer healing rate comparable to that of ranitidine, and no statistically significant difference was found between the two drugs [3].
• When administered twice daily at various doses (1-100 mg/kg) for 10 days, ebrotidine reduced dose dependently the area of chronic gastric ulcers, and it was accompanied by significantly higher contents of epidermal growth factor (EGF) in the ulcer bed than in the intact mucosa [4].
• The results show that administration of 500 mg/kg/day of ebrotidine for 18 mo to mice did not induce any hyperplastic effect on the gastric mucosa comprising its various cell types or any specific, diffuse, or focal hyperplasia of ECL cells [5].

Psychiatry related information on Ebrotidine

• Treatment with ebrotidine or ranitidine reduced significantly the endoscopic and self-assessment score, ebrotidine and ranitidine being equally effective in healing of esophageal mucosal lesions [6].

High impact information on Ebrotidine

• The inhibition of CYP3A4/5 enzyme activity by ebrotidine was competitive [7].
• In contrast, the effect of ranitidine or ebrotidine on CYP3A activity in vivo seems to have little clinical significance [7].
• Acute liver injury associated with the use of ebrotidine, a new H2-receptor antagonist [8].
• Gastric mucosal EGF and PDGF receptor expression with ulcer healing by ebrotidine [9].
• The purpose of this study was to assess the effect of the antiulcer agent, ebrotidine, on the expression of EGF and PDGF receptors with chronic ulcer healing [9].

Chemical compound and disease context of Ebrotidine

• Efficacy and safety of ebrotidine compared with ranitidine in patients with duodenal ulcer [3].
• Effect of ebrotidine on gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide [10].
• Cell cycle progression during gastric ulcer healing by ebrotidine and sucralfate [11].
• Thirty patients with rheumatic disease, who were divided into 5 groups, received an oral treatment of piroxicam 20 mg once daily for 6 days plus ebrotidine 400 mg/day (Group I); ebrotidine 800 mg/day (Group II); ranitidine 150 mg/day (Group III); ranitidine 300 mg/day (Group IV); or placebo (Group V) [12].

Biological context of Ebrotidine

• This phosphorylation process was inhibited by ebrotidine [13].
• To study the metabolism of ebrotidine in human urine, HPLC/MS with an atmospheric pressure chemical ionization (APCI) interface and simultaneous UV detection was conducted [2].
• In order to analyse biological samples containing ebrotidine and its biotransformation products, an HPLC/MS separation procedure with simultaneous UV detection was developed, allowing the identification of ebrotidine and its metabolites in human urine [14].
• The results point towards the importance of EGF in the maintenance of gastric mucosal calcium homeostasis, and suggest that ebrotidine has the ability to protect the cellular integrity from calcium imbalance by modulating the EGF-stimulated gastic mucosal calcium channel phosphorylation [15].
• Pharmacokinetics of ebrotidine in rats and dogs [16].

Anatomical context of Ebrotidine

• The possible hyperplastic effect on the mouse gastric mucosa following administration of 500 mg/kg of ebrotidine for 18 mo was investigated [5].
• We conclude that ebrotidine is highly effective inhibitor of basal, pentagastrin-induced and circadian gastric acid secretion in humans [17].
• Group A (six subjects) was treated for 3 days with either ebrotidine or placebo in a randomized, crossover study, and on the 4th day 100 ml of 50% ethanol was sprayed on the mucosa via an endoscope [18].
• The study of the population of antral G-cells was performed in a group of male rats treated with ebrotidine 500 mg/kg p.o. for 60 days; a control group receiving 10 ml/kg of an aqueous agar solution was used [19].
• Ebrotidine also exerts anti-Helicobacter pylori (Hp) effects by interfering with surface receptors of epithelial cells and inhibiting urease, protease and lipase activity, and by counteracting the noxious effects of Hp-related substances such as ammonia and lipopoly-saccharides (LPS) [20].

Associations of Ebrotidine with other chemical compounds

• The presence of ebrotidine and its metabolites ebrotidine S-oxide and 4-bromobenzenesulfonamide in human urine has been confirmed by HPLC separation and spectroscopic characterization of the collected fractions by FT-IR and 1H NMR [21].
• We also show that omeprazole, in contrast to sulglycotide and ebrotidine, fails to counter the enhancement in the mucosal expression of ECE-1 caused by H. pylori- lipopolysaccharide [22].
• The effect of antiulcer agents on the interference of lipopolysaccharide with the laminin receptor was found to be most efficiently countered by ebrotidine, sulglycotide and sucralfate, whereas sulglycotide is the most potent in the reversal of the inhibitory effect of the lipopolysaccharide on mucin receptor binding [23].
• Two groups of male rats were treated orally for 60 days with ebrotidine and cimetidine, used as reference standard, respectively [24].
• Comparative study of the safety and efficacy of ebrotidine versus ranitidine and placebo in the prevention of piroxicam-induced gastroduodenal lesions [12].

Gene context of Ebrotidine

• To test whether the inhibitory effect of ebrotidine in CYP3A activity was also found in vivo, we analyzed the biodisposition of midazolam in 8 healthy volunteers [7].
• The effects of ebrotidine on carbonic anhydrase in human subjects are reported [25].
• Improvements in mucus gel protective qualities with ebrotidine are directly related to the ability of the drug to enhance the synthesis and secretion of sulfo- and sialomucins and phospholipids of gastric mucus and to promote mucin macromolecular assembly [26].
• The mucosal expression of Cdk2 attained a maximum of 4.3-fold increase over that of the controls by the sixth day of healing with ebrotidine, and a fivefold increase in Cdk2 expression occurred by the fourth day of ulcer treatment with sucralfate [11].
• This activity of ebrotidine apparently stems from the drug's ability to counter the untoward effect of H. pylori on the binding of somatostatin to its specific receptor on the gastric mucosal G-cells [27].

Analytical, diagnostic and therapeutic context of Ebrotidine

• This study describes the application of capillary electrophoresis (CE) to the analysis of ebrotidine and its metabolites as an alternative analytical technique to liquid chromatography [28].
• Determination of ebrotidine and its metabolites by capillary electrophoresis with UV and mass spectrometry detection [28].
• Determination of ebrotidine and its metabolites by micellar electrokinetic capillary chromatography [29].
• In a double-blind randomized crossover study 10 male volunteers received treatment with either placebo plus ASA (500 mg) or ebrotidine (800 mg) plus ASA twice daily for 3 days with 10 days' washout period between treatments [30].
• The mean number of gastric erosions seen at endoscopy after treatment with ebrotidine plus ASA (2.0 +/- 0.3) was significantly lower than that after placebo plus ASA (3.7 +/- 0.2) [30].

References