Neutralization by ammonia cannot explain H. pylori's potentiation of Omeprazole's efficacy
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Objective To compare the efficacy of Dailixin plus omeprazole with that of omeprazole in the treatment of functional dyspepsia(FD),and three-month relapse of them.Methods 110 patients with FD were divided into observing group(n=60) and control group(n=50) randomly.The former group was administered with Dailixin and omeprazole,and the latter one with omeprazole.Their clinical symptoms were compared.Results The effective rate and three-month relapse rate were respectively 95.0% and 13.3% in the observing group,while the counterparts of the control group were 88.0% and 24.0%.There were significant differences in the parameters between the two groups(P0.05).Conclusion Dailixin plus omeprazole is safe and effective in the treatment of FD.Maintaining treament is required in many patients.
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The effect of omeprazole therapy in dyspepsia is unpredictable. The aim of this study was to identify patient characteristics and symptoms associated with the omeprazole response to improve selection of patients for empirical treatment with omeprazole.Data from a randomized controlled trial of 471 patients with ulcer-like or reflux-like dyspepsia treated with omeprazole 20 mg daily (243 patients) or placebo (228 patients) for 2 wk were studied using logistic regression analysis. The patients were randomly divided into a model sample (N = 236) for modeling the association between the omeprazole response and descriptive variables, and a test sample (N = 235) for testing the obtained model.In the model sample a high body mass index, the use of antacids or H2-blockers within the last month, or pain at night time were independently associated with a good omeprazole response, whereas the presence of nausea was associated with a poor omeprazole response. Using these variables combined into a therapeutic index, the independent test sample patients could be classified into predicted good (N = 56), medium (N = 88), and poor omeprazole responders (N = 91). In these groups the observed therapeutic gain of omeprazole (omeprazole response minus placebo response) was 39.4%, 19.3%, and 4.6%, respectively (p = 0.013). For clinical use, an easy-to-use pocket chart to obtain the therapeutic index in a given patient has been devised.In dyspepsia the identification of potential responders to omeprazole can be improved by considering certain patient characteristics and symptoms associated with the omeprazole response. Applying these data using a simple pocket chart may assist decision about empirical omeprazole therapy in patients with dyspepsia in general practice.
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ABSTRACT Background & Aims. The acid inhibitory effect of proton pump inhibitors is reported to be greater in the presence than in the absence of an H. pylori infection. This study was undertaken to test the hypothesis that the acid inhibitory effect of omeprazole given twice a day is greater in H. pylori infected healthy volunteers than in the same individuals following eradication because of differences in the pharmacodynamics of omeprazole, greater duodenogastric reflux, the effects of ammonia produced by the H. pylori , or lower gastric juice concentrations of selected cytokines, which may inhibit gastric acid secretion. Materials and Methods. We undertook 24 ‐ hour pH‐metry in 12 H. pylori ‐positive healthy volunteers: (1) when on no omeprazole; (2) when on omeprazole 20 mg bid for 8 days; (3) 2 months after eradication of H. pylori and when on no omeprazole; and (4) after eradication of H. pylori and when on omeprazole 20 mg twice a day. Results. In subjects given omeprazole, eradication of H. pylori reduced pH and percentage pH ≥ 3, as well as increasing the area under the H + concentration‐time curve. These differences were not due to alterations in (1) gastric juice concentrations of IL‐1α, IL‐8, IL‐13, epidermal growth factor, or bile acids; (2) serum gastrin concentrations; or (3) the pharmacokinetics of omeprazole. There was no change in the difference in the H + concentration‐time curve ‘without omeprazole’ minus ‘with omeprazole’, when comparing ‘after’ versus ‘before’ eradication of H. pylori . Conclusions. Eradication of H. pylori was not associated with an alteration in the acid inhibitory potency when comparing the difference in gastric acidity ‘with’ versus ‘without’ omeprazole. When the results were expressed by simply taking into account the acid measurements while on omeprazole before versus after eradication of H. pylori , the acid inhibition with omeprazole was greater in the presence than in the absence of a H. pylori infection. The clinical significance of the small difference is not clear.
Pharmacodynamics
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Esomeprazole
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Zollinger-Ellison syndrome
Basal (medicine)
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瞄准：与周期性的溃疡为十二指肠溃疡在外科以后流血在病人评估 omeprazole 维护治疗。方法：我们与周期性的溃疡为十二指肠溃疡在外科以后流血学习了 15 个连续病人。维护治疗在溃疡愈合以后被给的 Omeprazole (20 mg/d ) 。除了临床的后续，回廊 24-h 胃的 pH 试金与以前的十二指肠溃疡外科而是没有溃疡复发在那些病人和控制被执行在前并且在 omeprazole 治疗期间。结果：所有 15 溃疡在为 2 瞬间与 omeprazole (40 mg/d ) 被对待以后被愈合。有二的十一个病人(1-9 ) 周期性的溃疡流血的事件完成了后续(43， 12-72 瞬间) 。任何一个都没他们有一个流血事件当时在 omeprazole 上。一个病人中止了治疗并且有周期性的流血。在病人的胃的 pH<4 的中部的 24-h 部分时间是 80， 46-95% ，并且被归结为 32，由 omeprazole (P=0.002 ) 的 13-70% 。结论：有 omeprazole (20 mg/day ) 的长期的维护治疗在阻止周期性的溃疡流血是有效的。
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Crossover study
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Nonlinear kinetics of omeprazole and its metabolites were investigated after treatment with repeated high doses. Extensive metabolizers relating to cytochrome P450 2C19 (CYP2C19) activity received for 1 week either omeprazole at 40 mg/d (n = 14) or 60 mg/d omeprazole twice daily (n = 8). Five poor metabolizers (PMs) received 40 mg/d for 1 week. Comparison of omeprazole plasma kinetics between extensive metabolizers (EMs) and PMs after 40–mg treatment revealed a dominant role of CYP2C19 over cytochrome P450 3A CYP3A in omeprazole metabolism. Comparing the omeprazole doses of 40 mg and 60 mg in eight EMs on day 7 of treatment showed that CYP2C19–dependent plasma clearance of omeprazole and omeprazole sulfone was reduced from 19.0 to 8.4 L/h ( P < .001) and from 19.8 to 9.2 L/h ( P = .012), respectively. Similarly, formation half–life of 5′–hydroxyomeprazole increased from 0.58 to 1.45 hours ( P = .025) with the higher dose. CYP3A–dependent metabolic routes remained unaffected. Thus, high–dose treatment with omeprazole uncovers saturation kinetics for CYP2C19 pathways in EMs, and CYP3A becomes the predominant enzyme of omeprazole elimination. Moreover, these individuals may be at risk for side effects due to high omeprazole concentrations if high–dose omeprazole treatment is combined with drugs inhibiting CYP3A activity.
CYP3A
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Nonlinear kinetics of omeprazole and its metabolites were investigated after treatment with repeated high doses. Extensive metabolizers relating to cytochrome P450 2C19 (CYP2C19) activity received for 1 week either omeprazole at 40 mg/d (n = 14) or 60 mg/d omeprazole twice daily (n = 8). Five poor metabolizers (PMs) received 40 mg/d for 1 week. Comparison of omeprazole plasma kinetics between extensive metabolizers (EMs) and PMs after 40-mg treatment revealed a dominant role of CYP2C19 over cytochrome P450 3A CYP3A in omeprazole metabolism. Comparing the omeprazole doses of 40 mg and 60 mg in eight EMs on day 7 of treatment showed that CYP2C19-dependent plasma clearance of omeprazole and omeprazole sulfone was reduced from 19.0 to 8.4 L/h (P < .001) and from 19.8 to 9.2 L/h (P = .012), respectively. Similarly, formation half-life of 5′-hydroxyomeprazole increased from 0.58 to 1.45 hours (P = .025) with the higher dose. CYP3A-dependent metabolic routes remained unaffected. Thus, high-dose treatment with omeprazole uncovers saturation kinetics for CYP2C19 pathways in EMs, and CYP3A becomes the predominant enzyme of omeprazole elimination. Moreover, these individuals may be at risk for side effects due to high omeprazole concentrations if high-dose omeprazole treatment is combined with drugs inhibiting CYP3A activity.
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