Source: Medicines Authority (MT) Publisher: ESPECIALIDADES FARMACEUTICAS CENTRUM, S.A., By ASAC Pharma, C/Sagitario, 14, 03006 Alicante (Spain)
Ulcesep reduces gastric acid secretion through a unique mechanism of action. It is a specific inhibitor of the gastric proton pump in the parietal cell. It is rapidly acting and produces reversible control of gastric acid secretion with once daily dosing. Oral dosing with 20 mg Ulcesep once daily provides for rapid and effective inhibition of gastric acid secretion with maximum effect being achieved within 4 days of treatment. In duodenal ulcer patients, a mean decrease of approximately 80% in 24 hour intragastric acidity is then maintained, with the mean decrease in peak acid output after pentagastrin stimulation being about 70%, 24 hours after dosing with Ulcesep.
Clinical data for omeprazole in the prophylaxis of NSAID induced gastroduodenal lesions are derived from clinical studies of up to 6 months duration. Helicobacter pylori (Hp) is associated with acid peptic disease including duodenal ulcer (DU) and gastric ulcer (GU) in which about 95% and 80% of patients respectively are infected with this bacterium. Hp is implicated as a major contributing factor in the development of gastritis and ulcers in such patients. Recent evidence also suggests a causative link between Hp and gastric carcinoma. Omeprazole has been shown to have a bactericidal effect on Hp in vitro.
Eradication of Hp with omeprazole and antimicrobials is associated with rapid symptom relief, high rates of healing of any mucosal lesions, and long-term remission of peptic ulcer disease thus reducing complications such as gastrointestinal bleeding as well as the need for prolonged anti-secretory treatment.
In recent clinical data in patients with acute peptic ulcer omeprazole Hp eradication therapy improved patients' quality of life.
During long-term treatment an increased frequency of gastric glandular cysts have been reported. These changes are a physiological consequence of pronounced inhibition of acid secretion. The cysts are benign and appear to be reversible. No other treatment related mucosal changes have been observed in patients treated continuously with omeprazole for periods up to 5 years.
In a randomised study, with no comparator, the efficacy of 0.5 mg/kg, 1.0 mg/kg and 1.5 mg/kg of omeprazole was compared in 110 children aged 0-24 months with endoscopically and clinically diagnosed GORD. Due to the lack of placebo comparison no efficacy could be confirmed
In an uncontrolled, open-label dose-titration study, healing of severe erosive oesophagitis in children aged 1-16 years, approximately 65% of patients were healed with doses of 0.7-1.4 mg/kg.
In an uncontrolled, open-label study of omeprazole for the maintenance of healing of severe erosive oesophagitis in 46 children aged 1 to 16 yrs, 59% of patients relapsed on half their healing dose and they had to return to their healing dose. Helicobacter pylori eradication.
In a double-blind controlled parallel group study of 73 children aged 3 months to 15 years (mean age 10.5 years) with dyspeptic symptoms and H. pylori associated gastritis who were treated with triple therapy alone or in combination with omeprazole, the mean eradication rate was 74.2% in the omeprazole group compared with 9.4% in the placebo group. However, there was no evidence of clinical benefit demonstrated regarding dyspeptic symptoms.
Omeprazole is a weak base and is concentrated and converted to the active form in the acid environment of the intracellular canaliculi within the parietal cell, where it inhibits the enzyme H+, K+-ATPase – the proton pump. This effect on the final step of the gastric acid formation process is dose-dependent and provides for effective inhibition of both basal acid secretion and stimulated acid secretion irrespective of the stimulus.
All pharmacodynamic effects observed are explained by the effect of omeprazole on acid secretion.
Omeprazole is acid labile and is administered orally as enteric-coated granules in capsules. Absorption takes place in the small intestine and is usually completed within 3-6 hours. The systemic bioavailability of omeprazole from a single oral dose of Ulcesep is approximately 35%. After repeated once-daily administration, the bioavailability increases to about 60%. Concomitant intake of food has no influence on the bioavailability. The plasma protein binding of omeprazole is about 95%.
The average half-life of the terminal phase of the plasma concentration-time curve is approximately 40 minutes. There is no change in half-life during treatment. The inhibition of acid secretion is related to the area under the plasma concentration-time curve (AUC) but not to the actual plasma concentration at a given time.
Omeprazole is entirely metabolised mainly in the liver. Identified metabolites in plasma are the sulphone, the sulphide and hydroxy-omeprazole, these metabolites have no significant effect on acid secretion. About 80% of the metabolites are excreted in the urine and the rest in the faeces. The two main urinary metabolites are hydroxy-omeprazole and the corresponding carboxylic acid.
The systemic bioavailability of omeprazole is not significantly altered in patients with reduced renal function. The area under the plasma concentration-time curve is increased in patients with impaired liver function, but no tendency to accumulation of omeprazole has been found.
Limited data from children aged 0 16 years suggest that the pharmacokinetics within the recommended doses are similar to those reported in adults.
Gastric ECL-cell hyperplasia and carcinoids, have been observed in life-long studies in rats treated with omeprazole or subjected to partial fundectomy. These changes are the result of sustained hypergastrinaemia secondary to acid inhibition, and not from a direct effect of any individual drug.
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