Benzimidazoles

Elective esophageal variceal ligation (EVL) is performed to decrease the risk of variceal hemorrhage. Side effects of EVL include hemorrhage, chest pain, dysphagia, and odynophagia. Because gastric acid may exacerbate postbanding ulcers and delay healing, proton pump inhibition may decrease side effects associated with EVL. The aim of this study was to assess the efficacy of pantoprazole, a proton pump inhibitor, as an adjunct to elective EVL. We performed a double-blinded, randomized, placebo-controlled trial of pantoprazole after elective EVL. Subjects in the pantoprazole arm received 40 mg pantoprazole intravenously after EVL followed by 40 mg oral pantoprazole for 9 days. Control subjects received intravenous and oral placebo. Subjects underwent upper endoscopy 10 to 14 days after banding. Primary outcomes included the size and number of ulcers and the subjects' reports of dysphagia, chest pain, and heartburn. Forty-four subjects were randomized: 42 completed the protocol. At follow-up endoscopy, the mean number of ulcers was similar in the two groups. However, the ulcers in the pantoprazole group were on average half as large as in the placebo group (37 mm2 vs. 82 mm2, P < .01). Chest pain, dysphagia, and heartburn scores were not significantly different. Four subjects, all in the placebo group, had adverse outcomes, including 3 who bled from postbanding ulcers and 1 with sepsis. In conclusion, subjects receiving pantoprazole after elective EVL had significantly smaller postbanding ulcers on follow-up endoscopy than subjects receiving placebo. However, the total ulcer number and patient symptoms were not different between the groups. (HEPATOLOGY 2005;41:588–594.)

Involuntary weight loss, a part of the cachexia syndrome, is a debilitating co-morbidity of cancer and currently has no treatment options. Results from a recent clinical trial at our institution showed that biliary tract cancer patients treated with a MEK inhibitor exhibited poor tumor responses, but surprisingly gained weight and increased their skeletal muscle mass. This implied that MEK inhibition might be anti-cachectic. To test this potential effect of MEK inhibition, we utilized the established Colon-26 model of cancer cachexia and the MEK½ inhibitor MEK162. Results showed that MEK inhibition effectively prevented muscle wasting. Importantly, MEK162 retained its ability to spare muscle loss even in mice bearing a Colon-26 clone resistant to the MEK inhibitor, demonstrating that the effects of blocking MEK is at least in part independent of the tumor. Because single agent MEK inhibitors have been limited as a front-line targeted therapy due to compensatory activation of other o...

Elevated glucose concentration increases oxidation and Advanced Glycation End product (AGE) formation. The binding of circulatory AGEs or AGEs included in erythrocyte membrane to the receptor for AGEs (RAGE) generates in endothelial cells an oxidative stress and enhances the expression of inflammatory molecules. Engagement of RAGE by AGEs and subsequent signaling plays an important role in the development of diabetic complications. Soluble RAGE isoforms (sRAGE) neutralize the ligand-mediated damage by acting as a decoy. If the expression of RAGE is upregulated during the pathogenesis of inflammatory diseases, sRAGE mostly found decreased when complications ensue. By modulating RAGE isoform expression, it could be possible to reduce the incidence of complications. This review focused on the capability of Angiotensin Receptor Blockers (ARBs), which are used to treat patients with hypertension and/or diabetes, to modulate RAGE isoform expression because some data reported the interfere...

The aim of this study was to evaluate the accuracy of a new, continuous real time (13)C-urea breath test, BreathID, for the diagnosis of Helicobacter pylori in patients taking proton pump inhibitors (PPIs). Fifty-two consecutive patients, positive for H. pylori by BreathID, were prospectively evaluated. Patients were randomized to receive either omeprazole 20 mg/day or pantoprazole 40 mg/day for 14 days. A repeat breath test was performed on day 14 while patients received their last PPI pill. Patients were given a test drink containing 75 mg (13)C-urea and 4.0 g citric acid. Real time, continuously sampled expired (13)CO(2), obtained within 6-20 min, was compared with measurement of expired (13)CO(2) by isotope ratio mass spectrometry (IRMS). A full set of test data was available for 43 patients. After 14 days of treatment with PPIs, false negative detection of H. pylori occurred in only 1/43 (2.3%) patients examined by continuous real time (13)C-urea breath test compared with 2/43 ...

Background— Dabigatran, an oral thrombin inhibitor, and rivaroxaban and apixaban, oral factor Xa inhibitors, have been found to be safe and effective in reducing stroke risk in patients with atrial fibrillation. We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons. Methods and Results— We included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RELY]), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]), and rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF]), each compared with warfarin. The primary efficacy end point was stroke or systemic embolism; the safety end poi...

Mizolastine is a second generation antihistamine agent approved in Europe for the treatment of allergic rhinitis and skin conditions for which Sanofi~Synthélabo is developing a pediatric solution. Our objective was to design the population pharmacokinetic (PK) study of mizolastine pediatric solution in children. A bioavailability study of this solution compared to the marketed tablet was performed in 18 young volunteers. These PK data were analyzed by nonlinear regression using a two-compartment open model with zero-order absorption. From the estimated parameters, we designed population PK studies in two groups of children: 6 to 12 years and 2 to 6 years, respectively. To compare several population designs and to derive the optimal ones, we used the determinant of the Fisher information matrix of the population characteristics using a first-order expansion of the model. We have evaluated a “reference” population design with 10 samples (from 0.25 to 36 hr after drug intake) per child...

The most commonly occurring allergic diseases can involve a daytime drowsiness associated with the condition itself. The antihistamines used in their treatment can also have central effects and affect certain occupations concerned with risk, road safety and maritime and air navigation. Cognitive tests, experimental studies and epidemiological data recommend avoiding 1st generation antihistamines for people who must drive regularly and/or professions concerned with safety. Although there are no comparative studies on real driving between 1st and 2nd generation antihistamines, in this type of patients there should be a preference for prescribing those with least possible central effect, especially those which are a good substrate for transmembrane transporter pumps such as P-glycoprotein and therefore have a low capacity for crossing the hematoencephalic barrier, thus allowing a broader window for therapy. In this sense, bilastine is a good P-glycoprotein substrate and shows good tole...

The aim of this study was to compare the efficacy of esomeprazole and pantoprazole with regard to healing and relief from gastroesophageal reflux disease-related symptoms. I this multicentre, randomized, single-blind study 180 patients (ITT population) diagnosed with endoscopically proven GERD grade A,B,C received esomeprazole (40 mg once daily (o.d.), n = 90) orpantoprazole (40 mg o.d., n = 90). Healing and relief from GERD-related symptoms were assessed at first and final visit (after 4 or 8 weeks of treatment). Esomeprazole 40 mg provided significantly greater healing than pantoprazole 40 mg after 4 weeks of treatment in patients with EE (77.8% vs. 72.2%). Esomeprazole-treated patients were healed after up to 8 weeks of treatment similar those treated with pantoprazole (92.2% vs. 91.1%). The proportion of heartburn-free days was similar in patients treated with esomeprazole and to those treated with pantoprazole.

This study reports the reliability and validity of the distress subscale of the GERD Symptom Assessment Scale (GSAS) and the acute SF-36 Health Survey in a clinical trial setting. Patients with moderately severe GERD completed the GSAS and SF-36 at baseline and four weeks following treatment. The age (mean +/- SD) of the 187 patients was 45.5 +/- 11.1 years and most were female (63%) and Caucasian (78%). All scales met the 0.70 reliability criterion except for the SF-36 bodily pain scale. Mean baseline GSAS scores were significantly (P &lt; 0.001) poorer by 10-17% among patients reporting more severe levels of all symptoms. Mean baseline SF-36 physical component summary scores were significantly (P &lt; 0.02) poorer among patients reporting more severe levels of regurgitation, early satiety, bloating, and nausea. Patients reporting complete and satisfactory heartburn relief reported improvements in GSAS scores that were 13% and 10% greater, respectively, than patients who did not ex...

The compensation method and other chemometric methods (derivative, orthogonal function and difference spectrophotometry) have been applied to the direct determination of omeprazole, lansoprazole and pantoprazole in their pharmaceutical preparations. The methods have been validated; the limits of detection were found to be 3.3×10−2, 3.0×10−2 and 3.5×10−2 μg ml−1 for the three drugs, respectively. The repeatabililty of the methods were found to be 0.3–0.5%. The linearity ranges were found to be 0.5–3.5 μg ml−1. The proposed methods have been applied to the determination of the three drugs in their grastro-resistant formulations. The difference spectrophotometric (ΔA) method is unaffected by the presence of acid induced degradation products; hence can be used as a stability indicating assay.

The compensation method and other chemometric methods (derivative, orthogonal function and difference spectrophotometry) have been applied to the direct determination of omeprazole, lansoprazole and pantoprazole in their pharmaceutical preparations. The methods have been validated; the limits of detection were found to be 3.3×10−2, 3.0×10−2 and 3.5×10−2 μg ml−1 for the three drugs, respectively. The repeatabililty of the methods were found to be 0.3–0.5%. The linearity ranges were found to be 0.5–3.5 μg ml−1. The proposed methods have been applied to the determination of the three drugs in their grastro-resistant formulations. The difference spectrophotometric (ΔA) method is unaffected by the presence of acid induced degradation products; hence can be used as a stability indicating assay.

We investigated the effects of three different pesticides (carbendazim, dimethoate, and glyphosate) and their mixture on the growth and reproduction of the earthworm species, Eisenia fetida. The study was conducted following the suggestion of the International Workshop on Earthworm Ecotoxicology. The results showed that the pesticide treatment had a marked negative impact on the growth and reproduction of earthworms. Carbendazim and dimethoate were found to cause greater harm to the selected earthworm species than glyphosate.