Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article reviews the pharmacokinetics of esomeprazole, the (S)-isomer of the proton pump inhibitor (PPI) omeprazole. Esomeprazole is the first single isomer PPI developed for the treatment of patients with acid-related diseases. In vitro experiments in human liver microsomes demonstrated that the formation of the hydroxy and 5-O-desmethyl metabolites of esomeprazole is via cytochrome P450 (CYP) 2C19, whereas that of the sulphone metabolite is via CYP3A4. The formation rate of the hydroxy metabolite from esomeprazole is lower than for (R)-omeprazole, but that of the 2 other metabolites is higher, demonstrating stereoselective metabolism. The sum of the intrinsic clearances of all 3 metabo- lites for esomeprazole was one-third of that for (R)-omeprazole, suggesting lower clearance of esomeprazole in vivo. In vivo investigations demonstrated that esomeprazole is chirally stable after administration. Esomeprazole is 97% bound to plasma proteins. In normal (extensive) metabolisers with regard to CYP2C19, esomeprazole is metabolised more slowly than omeprazole, resulting in a higher area under the concentration-time curve (AUC) after administration of the same dose. This is more pronounced after repeated administration rather than after a single dose. In poor metabolisers, the AUC is lower for esomeprazole than for omeprazole, contributing to less overall interindividual variability for esomeprazole than for omeprazole. In general, esomeprazole and omeprazole are subject to the same metabolic transformations. Almost complete recoveries were reported and the ratio between urinary and faecal excretion is about 4:1 for both compounds. The dose-dependent increase in AUC of esomeprazole with repeated administration results from a combination of decreased first-pass elimination and decreased systemic clearance. Patients with gastro-oesophageal reflux disease exhibit a pharmacokinetic pattern similar to that in healthy individuals, whereas elderly individuals exhibited a slightly lower metabolism rate. Patients with a severe deficit in their liver function had a lower rate of metabolism, as would be expected, whereas those with mild to moderate liver disease did not exhibit any alteration in the pharmacokinetics. The pharmacokinetics of esomeprazole in individuals with impaired renal function is unlikely to differ from that in healthy individuals. A slight sex difference in the pharmacokinetics of esomeprazole was demonstrated in that the AUC and peak plasma drug concentration were slightly, but not statistically significantly, higher in females than in males.
 ...
PMID:Pharmacokinetic studies with esomeprazole, the (S)-isomer of omeprazole. 1147 67

Thirty one patients with asthma (mean age was 44.4 10.7; range 18-63) were investigated for gastroesophageal reflux (GER). The patients were separated into two groups according to presence of reflux and/or nocturnal symptoms. 13 patients had one of the reflux and/or nocturnal asthma symptoms (Group 1), whereas 18 patients had none of them (Group 2). To assess GER patients underwent to scintigraphy with Tc99m. GER was determined 4 of 13 patients in group 1 (30,7 %) and 1 of 18 patients in group 2 (5,5 %). There was significant difference between the group 1 and group 2 in that respect (p < 0,001). The patients with established GER (5 patients) were given Omeprazole (a proton pomp inhibitor) 40 mg daily for 4 weeks following a 2 week placebo period. The patients recorded their daily and nocturnal symptoms of asthma, additional salbutamol use, morning and evening peak expiratory flow rates (PEFR) measurements in a daily chart during placebo and omeprazole treatment without changing their antiasthma treatment. Their PEFR, FEV1 values, daily and nocturnal symptoms and additional beta agonist use did not changed after omeprazole treatment except one. But their reflux symptoms (heartburn and regurgitation) were improved. As a consequence, we suggested that asthmatics which have some complaints of reflux should be searched for GER. Not the respiratory functions but GER symptoms can be improved w
 ...
PMID:Gastroesophageal reflux in the patients with asthma. 1167 25

Gastric proton-pump inhibitors (PPIs) are prodrugs. Their acid activation at pH 1.0 inside the canaliculus of a parietal cell should be fast relative to their serum elimination rate. Actually, all PPIs display chemical activation half-lives at pH 1.0 of a few minutes at the most, while being eliminated from serum with a half-life of about 1 h. This is the main reason they show similar antisecretory efficacies on a milligram basis. It is in line with about 5% to 15% higher healing rates in GERD, DU and GU when 40 mg is compared to 20 mg of either omeprazole or pantoprazole. The comparably large biological variation between patient samples explains why some studies show statistically significant differences between the two doses, while others do not. However, it would matter to the individual patient if s/he was the one additionally healed by a 40 mg dose within a defined treatment period. Chemical activation of PPI prodrugs is unwanted in weakly acidic tissue compartments such as lysosomes or secretory granules. However, the ratio of the serum elimination half-life (availability at the target) to the chemical activation half-life at a critical pH 5.0 is reversed only with pantoprazole. when compared to pH 1.0 (i.e. the ratio is < 1 at pH 5.0 and > 1.0 at pH 1.0). This is the basis of the high pH selectivity of pantoprazole. In contrast, rabeprazole is activated at pH 5.0 almost as quickly as it is at pH 1.0 and much faster than it is eliminated from serum. This unwanted reactivity of rabeprazole at pH 5.0 does not contribute to the antisecretory action at pH 1.0 and results in poor pH selectivity. Omeprazole and lansoprazole lie in between, as they are activated, at pH 5.0, about as quickly as they are eliminated from serum. The above activation rates refer to room temperature. At 37 degrees C. the activation rates of all PPIs further increase, by about the same factor of between 3 and 4. This renders their differential pH selectivities even more critical for drug safety. Biological consequences have been reported in the literature. It has been claimed that a dose of 40 mg of the S-enantiomer of omeprazole (esomeprazole) results in 10%-15% higher healing rates in GERD patients, compared to 20 mg omeprazole racemate. The same difference is found when the two doses of omeprazole racemate are compared to each other. This is not surprising, as the chiral PPI prodrug is converted by acid into an achiral cyclic sulfenamide which only then reacts with the proton pump. There is therefore no pharmacodynamic argument in favour of any single enantiomer formulation of any PPI. Moreover, potential pharmacokinetic differences between the enantiomers seem to be of little if any importance in the patient.
 ...
PMID:Relative efficacies of gastric proton-pump inhibitors on a milligram basis: desired and undesired SH reactions. Impact of chirality. 1176 59

In August 1996, a 7-year-old boy was crushed from behind into the steering wheel of a go-cart, suffering a tear of his right innominate artery into the aortic arch, a 2-inch tear of the posterior trachea into left main bronchus, and 2 4-inch tears in the esophagus. These were all repaired on cardiopulmonary bypass through a sternotomy; a Gor-tex (W. L. Gore and Associates, Flagstaff, AZ) graft was required for the arterial repair. His recovery was complicated by a midesophageal stricture and a nearby fistula to the left main bronchus, which caused frequent lung infections and 12 hospital admissions over 2(1/2) years. During this time he had his stricture dilated 5 times and resected twice, his fistula surgically closed twice and glued 4 times, and an antireflux procedure, pyloroplasty, and gastrostomy for his persistent gastroesophageal reflux. He also had 2 esophageal stents placed; the first (titanium) lasted 4 months and the second (SILASTIC(R) [Dow Corning, Midland, MI]) 1 year later lasted 9 months, solving both the stricture and fistula problems and spontaneously passing through and out of his gastrointestinal tract. Throughout this recovery time, his nutrition was maintained mostly by gastrostomy feeding, supplemented by total parenteral nutrition and oral feeding when able. After 2(1/2) years of treatment, all has returned to normal, and he has remained well for the last 2(1/2) years (April 2001). He still is on Omeprazole.
 ...
PMID:Traumatic tear of aorta, trachea, and esophagus in a 7-year-old survivor. 1178 10

The recent introduction of proton pump inhibitors has extraordinarily improved the therapeutic approach to gastro-oesophageal reflux disease. The concept of decreasing gastric acid secretion and increasing the pH in the lower oesophagus has been demonstrated to be therapeutically effective and the higher the level of pH achieved, the better the results. In spite of the evident efficacy of these molecules, there are still many patients who will continue to have symptoms despite medical treatment. Proton pump inhibitors suppress gastric acidity, but this effect shows a remarkable interindividual variation depending on different reasons. Thus, it is still possible to optimise medical therapy for gastro-oesophageal reflux disease. Esomeprazole, the S-isomer of omeprazole, has an advantageous metabolism and this particular feature translates into superior clinical efficacy. Clinical trials for initial and long-term treatment across the gastro-oesophageal reflux disease spectrum, have clearly demonstrated the superiority of esomeprazole over omeprazole, even if tolerability and safety are very similar.
 ...
PMID:Improving opportunities for effective management of gastro-oesophageal reflux disease. 1178 20

Maintenance of intragastric pH > 4 is vital for effective management of gastroesophageal reflux disease (GERD). Esomeprazole 40 mg, the first proton pump inhibitor developed as an optical isomer, demonstrates improved acid inhibition over omeprazole 20 mg. Our aim was to compare esomeprazole 40 mg with omeprazole 40 mg, once-daily, on intragastric acidity in patients with symptoms of GERD. In this open-label, crossover study, 130 patients with symptoms of GERD received esomeprazole 40 mg or omeprazole 40 mg once-daily for five days. The 24-hr intragastric pH was monitored on days 1 and 5 of each treatment period. The mean percentage of the 24-hr period with intragastric pH > 4 was significantly greater (P < 0.001) with esomeprazole 40 mg than with omeprazole 40 mg on days 1 (48.6% vs 40.6%) and 5 (68.4% vs 62.0%). Interpatient variability was significantly less with esomeprazole than omeprazole. Esomeprazole was well tolerated. In conclusion, esomeprazole 40 mg provides more effective acid control than twice the standard dose of omeprazole.
 ...
PMID:Effect of esomeprazole 40 mg vs omeprazole 40 mg on 24-hour intragastric pH in patients with symptoms of gastroesophageal reflux disease. 1201 20

Esomeprazole, the S-isomer of omeprazole, is a new proton pump inhibitor. Esomeprazole provides better control of intragastric pH than omeprazole. It is more effective in treating erosive esophagitis in patients with GERD than omeprazole. Esomeprazole can maintain the healing of erosive esophagitis when used daily or on demand. It is also effective for the eradication of Helicobacter pylori infections. The incidence and type of adverse events associated with esomeprazole therapy are infrequent and likely to be similar to omeprazole.
 ...
PMID:Esomeprazole magnesium (Nexium). 1212 Jan 18

The pharmacology, pharmacodynamics, pharmacokinetics, clinical efficacy, and adverse effects of esomeprazole are reviewed. Esomeprazole, a proton-pump inhibitor (PPI), is the S-isomer of omeprazole. Esomeprazole has FDA-approved labeling for use in the treatment of symptomatic gastroesophageal reflux disease (GERD), including healing and maintenance of healing of erosive esophagitis and as part of a triple-drug regimen for Helicobocter pylori infection. Esomeprazole is structurally similar to other PPIs but is the first PPI to include only the active isomer, which may lead to improved pharmacokinetic and pharmacodynamic characteristics. Esomeprazole maintains intragastric pH at a higher level and above 4 for a longer period than other PPIs. Clinical studies have shown that esomeprazole is at least equivalent in safety and efficacy to other drugs in the class. Esomeprazole has demonstrated efficacy in the treatment of erosive esophagitis, the maintenance of healing of erosive esophagitis, and the treatment of signs and symptoms of GERD. Effective dosages are 20 or 40 mg orally every day or as needed. Esomeprazole magnesium 40 mg once daily in combination with amoxicillin and clarithromycin is effective in eradicating H. pylori infection. The potential for interacting with other drugs is limited and is similar to that of omeprazole. The most common adverse effects are headache, respiratory infection, and abdominal symptoms. Esomeprazole has pharmacokinetic properties that may make it more effective than omeprazole in some patients.
 ...
PMID:Esomeprazole: a clinical review. 1213 59

Esomeprazole is the last PPI registered on the Belgian market. It is the stable s-isomer of omeprazole. It has a better pharmacokinetic profile than omeprazole (racemate), allowing also better clinical performances. Esomeprazole is the first PPI shown superior to omeprazole in acute and chronic treatment of gastro-esophageal reflux disease. Controlled trials with this drug have also allowed to define new cost-effective strategies, such as on demand treatment for endoscopy-negative gastro-esophageal reflux and one week treatment of Helicobacter pylori positive duodenal ulcer.
 ...
PMID:[Pharma clinics medication of the month. Esomeprazole]. 1244 Mar 51

The proton pump inhibitors have consistently been shown to be far more effective than the others are in gastro-oesophageal reflux disease (GERD) as proton pump inhibitors (PPIs) block the final and rate-limiting step of parietal acid production. The primary objective of the study was to assess the efficacy and tolerability of esomeprazole 40 mg given once a day for 4 weeks in patients with reflux oesophagitis. An open, non-comparative study was done with 103 patients in 4 centres with endoscopic erosive oesophagitis. Symptoms of reflux oesophagitis such as heartburn/retrosternal pain and regurgitation recorded on a 4-point scale, dysphagia being marked as present or absent. Oesophagitis was graded as 5-point scale. There was a significant decrease in mean score of heartburn (60.8% and 86%), retrosternal pain (60.84% and 86.75%), mean score of regurgitation (65% and 90%) at second and fourth week respectively. Global assessment of overall symptoms by patients showed complete resolution of symptoms in 86.4% patients at week 4. At the end of treatment 93 out of 103 patients showed complete healing, 13.6% of total cases had side effects. Esomeprazole was found effective and safe in the treatment of GERD.
 ...
PMID:An open non-comparative clinical study for the evaluation of safety and efficacy of esomeprazole in patients of reflux oesophagitis in Indian population. 1245 20


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>