Inhibition Of Gastric Acid Secretion Research Articles

The retrospective analysis of 61 patients with ventilator-associated pneumonia

Objective To retrospectively analyze risk factor and outcome of VAP after treatment.Methods To retrospectively analyze the incidence of VAP in 249 patients accepted mechanical ventilation.Results Logistic regression analysis shew that age,APACHE Ⅱ scores,the time of mechanical ventilation,gastric acid secretion inhibitor therapy,conscious disturbance,combinations of antibiotics,stomach catheter insertion were associated risk factors for ventilator-associated pneumonia.A total of 91 pathogenic bacterium were identified.G pathogenic bacteriums accounted for 80.2% and G~+ pathogenic bacteriums accounted for 18.6% and true fungus accounted for 1.2%.Multidrug resistance was in most pathogenic bacteriums.All patients were treated with sensitive antibiotics and 39 cases were cured(63.9 %)and 22 cases were dead(36.1 %)after 2-6 weeks treatment.Conclusion Existence of risk factors of VAP are correlated with risk factor and G-pathogenic bacteriums are major pathogenic bacteriums and common drug resisitant microorganisma lead to bad outcome. Key words: Pneumonia,ventilator-associated; Drug resistance,bacterial; Risk factors

Dexlansoprazole for the treatment of esophagitis and GERD

Occasional acid reflux occurs frequently in the general population but gastroesophageal reflux disease (GERD), a chronic disease that affects millions of adults and children, is diagnosed if persistent reflux occurs more than twice a week. The development of proton pump inhibitors (PPIs) dramatically improved the treatment of GERD; however, the treatment of patients with refractory GERD remains a challenge. Dexlansoprazole (TAK-390MR, Kapidex), a pure enantiomer of lansoprazole, is a PPI that, with a novel dual delayed release formulation, provides prolonged inhibition of gastric acid secretion resulting in marked improvements in symptoms of GERD with high maintenance rates and good tolerability. Dexlansoprazole recently received Food and Drug Administration approval for the once-daily oral treatment of heartburn associated with symptomatic nonerosive GERD, the healing of erosive esophagitis (EE) and the maintenance of healed EE.

Regulation of Gastric Acid Secretion by PKB/Akt2

Pharmacological inhibition of phosphoinositol 3 kinase (PI3K) and partial deficiency of phosphoinositide dependent kinase PDK1 have previously been shown to enhance basal gastric acid secretion. PI3K/PDK1 dependent signaling involves activation of protein kinase B/Akt, which may thus be similarly involved in the regulation of gastric acid secretion. To test that hypothesis, gastric acid secretion was determined in isolated glands from gene targeted mice lacking functional Akt2 (akt2^-/-) or from their wild type littermates (akt2^+/+). According to BCECF-fluorescence cytosolic pH in isolated gastric glands was similar in akt2^-/- and akt2^+/+ mice. Na⁺-independent pH recovery (ΔpH/min) following an ammonium pulse, a measure of H⁺/K⁺ ATPase activity, was, however, significantly faster in akt2^-/- than in akt2^+/+ mice. In both genotypes, ΔpH/min was virtually abolished by H⁺/K⁺ ATPase inhibitor omeprazole (100 µM). Increase of extracellular K⁺ concentrations to 35 mM (replacing Na⁺) increased ΔpH/min to a significantly larger extent in akt2^+/+ than in akt2^-/- mice and dissipated the differences between the genotypes. Similarly, treatment with 5 µM forskolin enhanced ΔpH/min significantly only in akt2^+/+ mice and abolished the differences between the genotypes. Conversely, protein kinase A inhibitor H89 (50 nM) decreased ΔpH/min to similarly low values in both genotypes. In conclusion, Akt2 suppresses gastric acid secretion and contributes to or even accounts for the inhibition of gastric acid secretion by PI3K.

α 2-Adrenoceptor subtypes-mediated physiological, pharmacological actions

α 2-Adrenoceptors are involved in various physiological functions, particularly in the cardiovascular system and the central nervous system. Different adrenoceptor subtypes (α 2A, α 2B and α 2C) have been recognised and the different subtypes may have role in activation of distinct physiological and pharmacological pathways. Some of the actions of α 2-adrenoceptor stimulants are likely to be mediated exclusively by α 2A-adrenoceptor subtype, like antihypertensive and bradycardic effects. α 2A-Adrenoceptor may have dominant role in sedative and hypothermic actions, in inhibition of gastric acid secretion and gastric motor activity, as well as in stabilisation of thrombus. Besides α 2A-adrenergic receptors α 2B and α 2C-adrenoceptor subtypes may also be involved in some of the classical effects of α 2-adrenoceptor stimulants, like in presynaptic regulation of transmitter release and antinociceptive action. α 2B-Adrenoceptor has dominant role in the vasoconstrictor effect of α 2-adrenoceptor agonists, and its activation induces contraction of rat uterus in late pregnancy. α 2B-Adrenoceptor mediates gastric mucosal protective action initiated centrally in the rat, as well as it may have role also in developmental or reproductive processes. α 2C-Adrenoceptor subtypes may be involved in stress-dependent depression and other psychiatric illnesses like attention deficit hyperactivity disorder—together with α 2A-adrenoceptor. α 2C-Adrenergic receptors seem to mediate peripheral actions as well, like venous vasoconstriction. Identification of separate physiological roles for different α 2-adrenergic receptor subtypes could improve design of novel compounds for specific therapeutic goals.

W1542 Effect of Carbon Monoxide On HCO3- Secretion in Rat Stomachs: Involvement of Heme Oxygenase in Regulation of Gastric HCO3- Response

G A A b st ra ct s -/mice to wild type mice to determine if zinc works via the receptor or by direct interactions within the cytosol. Material and methods: Wild type and CaSR-deficient mice were fasted for 12-18 hours prior to sacrifice to ensure a consistent minimum of gastric acid secretion. Single gastric glands were hand-dissected from the corpus of the stomach. After incubation with the pH-sensitive dye, BCECF glands were transferred to a coverslip precoated with a biological cell adhesive, mounted in a chamber maintained at 37° and then imaged on a real time fluorescence digital system. For reproducible acidification, glands were exposed to a Na+-free NH4Cl prepulse and a 0 mM Na+ solution. Following acid loading and Na+removal, acid extrusion was monitored as rate of intracellular alkalinization. To examine proton extrusion by H+,K+-ATPase and to preclude contribution of Na+/H+ exchange, Na+free conditions were chosen. The rate of pH recovery, representing H+,K+-ATPase activity, was calculated as ΔpHi/Δt, using a high-K+/Nigericin calibration technique. In wild type mice Histamine or a potent calcimimetic activator of the CaSR, were used to stimulate acid secretion. In CaSR-deficient mice Histamine alone was used. In a subsequent series of experiments Zinc was added. Results: In the presence of functional CaSR the inhibitory effect of Zinc on gastric acid secretion was significantly higher than that seen in CaSRdeficient mice, suggesting the primary pathway for zinc action is at the level of the CaSR. Conclusion: This study shows the predominant role of the CaSR in Zinc-mediated inhibition of gastric acid secretion. Additionally this study suggests the importance of dietary zinc to modulate acid production. Failure to have sufficient zinc in the diet would result in reduced serum levels of zinc. This reduction in zinc could lead to an enhanced CaSR function and subsequent gastric acid hypersecretion even in the absence of hormonal or neuronal stimulation.

CASE OF INFLAMMATORY FIBROID POLYP OF THE ESOPHAGOGASTRIC JUNCTION

Upper gastrointestinal endoscopy of a 25-year-old man with heartburn revealed an elevated lesion in the esophagogastric junction (EGJ). Piecemeal endoscopic mucosal resection (EMR) followed by histopathological examination led to a diagnosis of inflammatory fibroid polyp (IFP). After EMR, the heartburn persisted despite giving a proton pump inhibitor (PPI), and the residual lesion gradually enlarged and a transverse mucosal break developed on the esophageal side of it. However, the combined administration of the PPI and an H2 receptor antagonist reduced the heartburn, and led to endoscopic regression of the lesion and disappearance of the transverse mucosal break. IFP of the esophagogastric junction is extremely rare, and this case is interesting in that potent inhibition of gastric acid secretion resulted in the regression of the lesion.

Reflections on some pilot trials of gastrin receptor blockade in pancreatic cancer

The experience of synthesising a novel gastrin receptor antagonist gastrazole and taking it into 3 small clinical studies in pancreatic cancer in man is described. The need for such a compound is illustrated by the observation that inhibition of gastric acid secretion by H2 receptor antagonists results in hypergastrinaemia. A large number of cell types have gastrin receptors including pancreatic cancer cells which have been shown to be stimulated by gastrin. Small numbers of pancreatic cancer patients given gastrazole by continuous intravenous infusion showed prolonged survival compared with best supportive care or placebo, and equivalent survival to those given 5 fluouracil. The results suggest a greater benefit for patients with early stage disease. An alternative gastrin receptor antagonist YF 476 is also described which has the advantage of efficacy given by the oral route. This new compound requires to be studied in pancreatic cancer and other diseases associated with hypergastrinaemia.

Inhibition of gastric acid secretion by Ya-hom in isolated mouse whole stomach

Background: Ya-hom, the traditional Thai formula for abdominal discomfort treatment has, been reported to inhibit gastric acid secretion in gastric fistula rats. However, the mechanism underlying its action remains unclear. Objective: To investigate the gastric acid inhibitory action of Ya-hom and its mechanism of action by using an isolated mouse whole stomach model. Methods: The gastric acid secretion of isolated mouse whole stomach was stimulated by histamine (5.0 μM) or bethanechol (10 or 100 μM) after adding the inhibitors (atropine 1 μM, ranitidine 10 μM, indomethacin 0.1 μM or L-NAME 300 μM) and/or Ya-hom to the serosal solution. The effluent perfusate was collected continuously in 10-minute fractions for 120 minutes after stimulation. Results: Re-dissolved lyophilized Ya-hom extract at doses of 2.5, 5.0, 10.0, and 20.0 mg/mL inhibited histaminestimulated gastric acid secretion in a dose-dependent manner. Inhibition of Ya-hom (10 mg/mL) was also observed in the presence of atropine (1 μM), which was used to eliminate effects of endogenous acetylcholine. Ya-hom inhibited bethanechol-stimulated gastric acid secretion in the presence and absence of ranitidine. While the inhibitory action of Ya-hom on histamine-stimulated gastric secretion was not affected by indomethacin, it was attenuated by concomitant treatment with the nitric oxide synthase inhibitor (L-NAME). Conclusion: Ya-hom did not stimulate gastric acid secretion in the isolated mouse whole stomach. Ya-hom significantly inhibited gastric acid secretion after this was stimulated via histamine or bethanechol. Nitric oxide stimulation plays an important role in the inhibitory action of Ya-hom.

Analysis of omeprazole and its main metabolites by liquid chromatography using hybrid micellar mobile phases

Omeprazole is a selective inhibitor of gastric acid secretion and is one of the most widely prescribed drugs internationally. A chromatographic procedure that uses micellar mobile phases of sodium dodecyl sulphate and propanol buffered at pH 7 and a C18 column is reported for the determination of omeprazole and its principal metabolites (omeprazole sulphone and hydroxyomeprazole) in urine and serum samples. In this work, direct injection and UV detection set at 305 nm was used. Omeprazole and its metabolites were eluted in less than 11 min with no interference by the protein band or endogenous compounds. Adequate resolution was obtained with a chemometric approach, in which the retention factor and shape of the chromatographic peaks were taken into account. The analytical parameters including linearity ( r > 0.9998), intra- and inter-day precision (RSD, %: 0.6–7.9 and 0.14–4.7, respectively) and robustness were studied in the validation of the method for the three compounds. The limits of detection and quantification were less than 6 and 25 ng mL −1, respectively. Recoveries in micellar medium, plasma and urine matrices were in the 98–102% range. Finally, the method was successfully applied to the determination of omeprazole and its metabolites in physiological samples. Omeprazole was also analysed in pharmaceutical formulations.

Is There a Dark Side to Long-term Proton Pump Inhibitor Therapy?

Proton pump inhibitors (PPIs) are among the most widely used of prescription drugs. They have revolutionized the management of gastroesophageal reflux disease and other acid-related disorders. Although generally safe, concerns about possible adverse effects continue to arise. Some of these, such as gastric neoplasms, are of theoretical concern only and are related to suppression of gastric acid secretion and consequent hypergastrinemia; these have not been encountered in clinical practice despite millions of patient-years of use. Others are more idiosyncratic, unpredictable, and rare. In general, the therapeutic benefits of PPIs outweigh these potential risks. However, it is important that PPIs are only given for appropriate indications and that, whenever possible, they are used in the lowest effective dose. At present, there is no need for specific monitoring for adverse events during PPI therapy.

Spiro(imidazo[1,2- a]pyrano[2,3- c]pyridine-9-indenes) as inhibitors of gastric acid secretion

Asymmetric and symmetric spiro(imidazo[1,2- a]pyrano[2,3- c]pyridine-9-indenes) were prepared using a synthetic approach that comprised a cross-metathesis reaction and an acid-catalyzed cycloisomerisation as key steps. The target compounds constitute potent inhibitors of the gastric proton pump enzyme with inhibitory activity comparable to potassium-competitive acid blockers (P-CABs) belonging to the known 9-aryl-7 H-8,9-dihydropyrano[2,3- c]imidazo[1,2- a]pyridine series. Spiro(imidazo[1,2- a]pyrano[2,3- c]pyridine-9,2′-indenes) represent the first example for P-CABs, in which the distance between the heterocyclic scaffold and the aryl residue has been modified, and are promising candidates for further development as anti-ulcer drugs.

Release of regulatory gut peptides somatostatin, neurotensin and vasoactive intestinal peptide by acid and hyperosmolal solutions in the intestine in conscious rats

The impact of exposure of the intestinal mucosa to acid and hyperosmolal solutions on the release of the inhibitory gut peptides somatostatin (SOM), neurotensin (NT) and vasoactive intestinal peptide (VIP) was studied in conscious rats during pentagastrin-stimulated gastric acid secretion. The animals were equipped with a chronic gastric fistula to measure acid secretion and a jejunal Thiry–Vella loop for intestinal challenge with saline, hydrochloric acid (HCl, 200 mmol L − 1 ) or hyperosmolal polyethylene glycol (PEG, 1200 mOsm kg − 1 ). Gut peptide concentrations were measured in intestinal perfusates, and in plasma samples collected during stimulated acid secretion, and at the end of experiments with luminal challenge of the loops. After pentagastrin-stimulation acid secretion was dose-dependently inhibited by intravenous administration of the gastrin receptor antagonist gastrazole, as well as ranitidine and esomeprazole by maximally 73 ± 10%; 95 ± 3%; 90 ± 10%, respectively. Acid perfusion of the Thiry–Vella loop caused a prominent release of SOM both to the lumen (from 7.2 ± 5.0 to 1279 ± 580 pmol L − 1 ) and to the circulation (from 18 ± 5.2 to 51 ± 9.0 pmol L − 1 ) simultaneously with an inhibition of gastric acid secretion. The release of NT and VIP was not affected to the same extent. PEG perfusion of the loop caused a release of SOM as well as NT and VIP, but less. Simultaneously acid secretion was slightly decreased. In conclusion, intestinal perfusion with acid or hyperosmolal solutions mainly releases SOM, which seems to exert a major inhibitory action in the gut, as shown by inhibition of acid secretion. The other peptides NT and VIP also participate in this action but to a much lesser degree. The operative pathways of these gut peptides hence involve both endocrine (SOM) and paracrine actions (SOM, NT, VIP) in order to exert inhibitory functions on the stomach. The inhibitory action of gastrazole, was in a similar range as that of SOM implying that physiological acid-induced inhibition of gastric acid may primarily be exerted through inhibition of gastrin endocrine secretion.

Gastroösophageale Refluxerkrankung

Gastroesophageal reflux disease (GERD) is present when the passage of gastric contents into the esophagus causes symptoms or mucosal damage. Potent suppression of gastric acid secretion with proton pump inhibitors (PPIs) is an effective and safe treatment for many patients with this condition; however, acid suppression has not solved the problem of GERD. The relationship between reflux symptoms, endoscopic findings, and esophageal acid exposure is not straightforward. Some patients fail to respond to PPIs; at endoscopy, the esophagus is often normal, and pH studies may not reveal the cause of symptoms. It is clear that, although gastric acid secretion can be suppressed, we are far less successful at managing reflux itself.Apart from „typical” reflux symptoms, other complaints, including dysphagia, noncardiac chest pain, and chronic cough, have been linked to GERD, but it can be difficult to identify those patients who will benefit from antireflux treatment. This is relevant because the risk of esophageal adenocarcinoma is elevated in patients with reflux symptoms, in particular those with Barrett’s esophagus.

American Gastroenterological Association Institute Technical Review on the Management of Gastroesophageal Reflux Disease

American Gastroenterological Association Institute Technical Review on the Management of Gastroesophageal Reflux Disease

Review: Causes of, and therapeutic approaches for, proton pump inhibitor-resistant gastroesophageal reflux disease in Asia

Proton pump inhibitors (PPIs) are the most widely used drugs for treatment of gastroesophageal reflux disease. However, approximately 20% of patients with reflux esophagitis and 40% of those with nonerosive reflux diseases complain of troublesome symptoms, even during treatment with PPIs. In patients with reflux esophagitis, dose escalation and co-administration with a histamine H(2)-receptor antagonist are potential approaches, since the major cause of PPI resistance is incomplete suppression of gastric acid secretion. On the other hand, for patients with nonerosive reflux disease, switching from PPIs to pain modulators is often necessary for improvement of symptoms, since 25% of patients with nonerosive reflux disease have symptoms not caused by gastroesophageal acid reflux. Therapeutic approaches for PPI-resistant patients with reflux esophagitis and nonerosive reflux diseases are considered according to pathogenesis.

The Interrelationship Between Gastric pH and Therapeutic Response to Esomeprazole in Patients with Uninvestigated Dyspepsia

Purpose: Management of dyspepsia remains a challenge both in research and clinical practice. Pharmacological therapy, targeting gastric acid suppression results in relief of symptoms in majority of patients complaining of epigastric pain/discomfort related to uninvestigated dyspepsia; however, the relationship between symptom relief and the degree of acid suppression has not been adequately explored. Therefore, the aims of the study were as follows: 1. To evaluate the impact of esomeprazole vs. placebo on gastric acid during 24 h pH monitoring. 2. To asses the relationship between relief of dyspepsia symptoms and changes in gastric pH. Methods: This randomized, double-blind trial was conducted on KUMC patients with uninvestigated dyspepsia, diagnosed acc. to Rome II criteria, with at least moderately severe symptoms of epigastric pain/discomfort. Patients with heartburn or regurgitation as their predominant symptoms, H. pylori (+) or aspirin-like drugs users were excluded. Patients (mean age of 44.2; 62.2% F) were randomized to placebo (N = 35) or esomeprazole (N = 38) 40 mg QD groups. Primary outcome measures were satisfactory relief of pain/discomfort symptoms, a 7-day daily diary preceding each visit, quality of life questionnaire, and global overall symptoms assessment. Gastric pH was monitored for 24 h at baseline and after 4 and 8 weeks of therapy, using dual probe catheter and pH Monitoring System (Sandhill Sci.). Results: Both responders (R) and non-responders (NR) exhibited similar baseline gastric acid secretion at distal (D) and proximal (P) probes: (pH > 4.0 in min) 201 min RD, 177 min NRD, 641 min RP, and 628 min NRP, respectively. Administration of esomeprazole for 4 weeks resulted in profound inhibition of gastric acid secretion reflected by significant (P < 0.01) increase in time pH > 4.0 both among R and NR at D and P pH probe locations. During 2nd therapy interval R exhibited, however, higher degree of gastric acid inhibition, 361% (P < 0.001) increase of time pH >4.0 over baseline value in D probe, whereas NR only 157% (P= 0.12) increase. Higher degree of gastric acid inhibition, 162% (P < 0.001) over baseline value, was also revealed in the P probe in R vs. only 97% increase in NR (P= 0.22). Conclusion: 1. Intragastric pH monitoring before and after therapy may help to address interrelationship between symptomatic relief of dyspepsia symptoms and gastric acid secretion inhibition and could potentially help to tailor individual therapy. 2. Esomeprazole, 40 QD, provides profound inhibition of gastric acid secretion as reflected in time pH > 4.0 in patient with dyspepsia accompanied by significant relief of symptoms.

Inhibition of gastric acid secretion by a standardized aqueous extract of Cecropia glaziovii Sneth and underlying mechanism

Cecropia glazioui Sneth (Cecropiaceae) is used in folk medicine in tropical and subtropical Latin America as cardiotonic, diuretic, hypotensive, anti-inflammatory and anti-asthmatic. The hypotensive/antihypertensive activity of the plant aqueous extract (AE) and isolated butanolic fraction (BuF) has been confirmed and putatively related to calcium channels blockade in vascular smooth musculature [Lapa, A.J., Lima-Landman, M.T.R., Cysneiros, R.M, Borges, A.C.R., Souccar, C., Barreta, I.P., Lima, T.C.M., 1999. The Brazilian folk medicine program to validate medicinal plants - a topic in new antihypertensive drug research. In: Hostettman, K., Gupta, M.P., Marston, A. (Eds.), Proceedings Volume, IOCD/CYTED Symposium, Panamá City, Panamá, 23-26 February 1997. Chemistry, Biological and Pharmacological Properties of Medicinal Plants from the Americas. Harwood Academic Publishers, Amsterdam, pp. 185-196; Lima-Landman, M.T., Borges, A.C., Cysneiros, R.M., De Lima, T.C., Souccar, C., Lapa, A.J., 2007. Antihypertensive effect of a standardized aqueous extract of Cecropia glaziovii Sneth in rats: an in vivo approach to the hypotensive mechanism. Phytomedicine 14, 314-320]. Bronchodilation and antidepressant-like activities of both AE and BuF have been also shown [Delarcina, S., Lima-Landman, M.T., Souccar, C., Cysneiros, R.M., Tanae, M.M., Lapa, A.J., 2007. Inhibition of histamine-induced bronchospasm in guinea pigs treated with Cecropia glaziovi Sneth and correlation with the in vitro activity in tracheal muscles. Phytomedicine 14, 328-332; Rocha, F.F., Lima-Landman, M.T., Souccar, C., Tanae, M.M., De Lima, T.C., Lapa, A.J., 2007. Antidepressant-like effect of Cecropia glazioui Sneth and its constituents -in vivo and in vitro characterization of the underlying mechanism. Phytomedicine 14, 396-402]. This study reports the antiulcer and antisecretory gastric acid activities of the plant AE, its BuF and isolated compounds with the possible mechanism involved. Both AE and BuF were assayed on gastric acid secretion of pylorus-ligated mice, on acute models of gastric mucosal lesions, and on rabbit gastric H(+), K(+)-ATPase preparations. Intraduodenal injection of AE or BuF (0.5-2.0g/kg, i.d) produced a dose-related decrease of the basal gastric acid secretion in 4-h pylorus-ligated mice. At 1.0g/kg, BuF decreased the volume (28%) and total acidity (33%) of the basal acid secretion, and reversed the histamine (2.5mg/kg, s.c.)- or bethanecol (1.0mg/kg, s.c.)-induced acid secretion to basal values, indicating inhibition of the gastric proton pump. Pretreatment of mice with the BuF (0.05-0.5g/kg, p.o.) protected against gastric mucosal lesions induced by 75% ethanol, indomethacin (30mg/kg, s.c.) or restraint at 4 degrees C. BuF also decreased the gastric H(+), K(+)-ATPase activity in vitro proportionately to the concentration (IC(50)=58.8microg/ml). The compounds isolated from BuF, consisting mainly of cathechins, procyanidins and flavonoids [Tanae, M.M., Lima-Landman, M.T.R., De Lima, T.C.M., Souccar, C., Lapa, A.J., 2007. Chemical standardization of the aqueous extract of Cecropia glaziovii Sneth endowed with antihypertensive, bronchodilator, antacid secretion and antidepressant-like activities. Phytomedicine 14, 309-313], inhibited the in vitro gastric H(+), K(+)-ATPase activity at equieffective concentrations to that of BuF. The results indicate that C. glazioui constituents inhibit the gastric proton pump; this effect may account for the effective antisecretory and antiulcer activities of the standardized plant extract.

Stronger inhibition of gastric acid secretion by lafutidine, a novel H2 receptor antagonist, than by the proton pump inhibitor lansoprazole

To compare the antisecretory activity and plasma drug concentrations of a single oral dose of 10 mg lafutidine, a novel H2 receptor antagonist, with those of the proton pump inhibitor lansoprazole (LPZ) 30 mg. Ten volunteers without H pylori infection participated in this crossover study comparing lafutidine 10 mg with LPZ 30 mg. Intragastric pH was monitored for 6 h in all participants, and blood samples were collected from four randomly selected individuals after single-dose administration of each drug. The median intragastric pH was significantly higher in individuals who received lafutidine 10 mg than in those who received LPZ 30 mg 2, 3, 4, 5, and 6 h after administration. Maximal plasma drug concentration was reached more promptly with lafutidine 10 mg than with LPZ 30 mg. In H pylori-negative individuals, gastric acid secretion is more markedly inhibited by lafutidine than by LPZ.

Clinical Efficacy of Esomeprazole in the Prevention and Healing of Gastrointestinal Toxicity Associated with NSAIDs in Elderly Patients

NSAIDs are widely prescribed for the treatment of pain, inflammation and rheumatic disorders, but their use is associated with adverse gastrointestinal effects, ranging from dyspeptic symptoms and peptic ulcers to more serious complications. Elderly patients are at high risk of experiencing NSAID-induced gastrointestinal tract injury and should be considered candidates for prophylactic pharmacological therapy. In studies conducted in adult patients, proton pump inhibitors (PPIs) such as esomeprazole have been shown to prevent or reduce NSAID-induced gastrointestinal injury. The beneficial effects of esomeprazole can be ascribed largely to its ability to maintain sustained inhibition of gastric acid secretion, although there is evidence to suggest that pharmacodynamic properties unrelated to acid inhibition may also contribute to the gastroprotective effects of this agent. Although there are limited data on the use of esomeprazole specifically in elderly patient populations, studies of patients at high risk of NSAID-induced gastrointestinal toxicity because of advanced age indicate that this PPI is both effective and well tolerated when administered in conjunction with NSAIDs. Thus, esomeprazole can be regarded as a useful option for prophylactic therapy in elderly patients receiving long-term NSAID therapy.

Early effects of Lansoprazole orally disintegrating tablets on intragastric pH in CYP2C19 extensive metabolizers

To compare rabeprazole (RPZ; 10 mg) with Lansoprazole orally disintegrating tablets (LPZ; 30 mg OD) in terms of antisecretory activity and blood drug concentration after a single dose. Eight H pylori -negative cytochrome P450 (CYP) 2C19 extensive metabolizers were assigned to receive a single oral dose of RPZ 10 mg or LPZ 30 mg OD. Twelve hour intragastric pH monitoring was performed on the day of treatment. Blood samples were also collected after the administration of each drug. LPZ 30 mg OD induced a significantly earlier rise in blood drug concentration than RPZ 10 mg; consequently, LPZ 30 mg OD induced a significantly earlier rise in median pH in the third and fourth hours of the study. In H pylori-negative CYP2C19 extensive metabolizers, LPZ 30 mg OD induced a significantly faster inhibition of gastric acid secretion than RPZ 10 mg.