Omeprazole: A Comprehensive Review

Omeprazole is a member of a new class of substituted benzimidazoles. These agents inhibit the proton pump in the gastric parietal cell, blocking the final step in the gastric acid secretory pathway. Omeprazole has been investigated for the treatment of gastric ulcer, duodenal ulcer, gastroesophageal reflux, and various hypersecretory states. The prolonged inhibition of gastric acid secretion allows for once-daily dosing in patients with peptic ulcer disease and gastroesophageal reflux, and once- or twice-daily dosing in patients with Zollinger-Ellison syndrome. Compared with currently available therapies, omeprazole is well tolerated and demonstrates a more rapid ulcer healing rate. It is superior to conventional therapies in the treatment of Zollinger-Ellison syndrome. Side effects are infrequent when the drug is used for the short-term management of ulcers.     

兰索拉唑药理与毒理研究进展

目的：明确兰索拉唑药理和毒理作用特点,为其临床用药提供参考。方法：通过对近十几年来兰索拉唑国内外相关文献进行整理、归纳与分析,综述兰索拉唑的构效特点、对消化系统的药理作用及对机体产生的毒理作用。结果：兰索拉唑具有保护胃黏膜、抑制溃疡形成、促进溃疡愈合、抗幽门螺杆菌等药理作用；毒理学研究表明兰索拉唑有潜在致癌风险。结论：应在观察上市后的兰索拉唑用药风险的基础上,进一步深入研究其毒理学特点和药物之间的相互作用,以便为临床不良反应发生做出合理解释和寻找有效解决办法,确保保证兰索拉唑临床用药的安全性、合理性和高效性。     

兰索拉唑

<正> 1 概述兰索拉隆的化学式为C_(16)H_(14)F_3N_3O_2S,原料药为白色或呈白褐色的无味晶体粉末。本品一般为缓释制剂,两种规格:15mg/粒和30mg/粒,内含药物的肠溶颗粒。2 药理学资料2.1 药物代谢动力学兰索拉唑的缓释胶囊含药物的肠溶包衣颗粒,进入肠道后开始释放药物且吸收迅速,口服该药1.7h后血中药物达到峰浓度。单剂量口服该药15～60mg后其血浆药物峰浓度(Cmax)与药-时曲线下面积     

HPLC法测定兰索拉唑胶囊中兰索拉唑的含量

目的建立并优化测定兰索拉唑胶囊中兰索拉唑含量的高效液相色谱法。方法色谱柱为依利特C18(4.6 mm×250mm,5μm),流动相为乙腈-0.1 mol.L-1磷酸盐缓冲液(pH7.2)(75∶25),检测波长为285 nm。结果兰索拉唑在浓度为线性范围为8～160 mg.L-1,相关系数为0.999 9,平均加样回收率为100.1%,RSD=1.19%。结论该方法操作简单、快速、准确,可用于兰索拉唑胶囊中兰索拉唑的含量测定。     

HPLC法测定注射用兰索拉唑的有关物质及主药含量

目的:建立注射用兰索拉唑含量及有关物质的反相高效液相色谱(RP-HPLC)测定法.方法:采用Agilent Eclipse XDB-C8色谱柱,三乙胺水溶液[取三乙胺10 ml,加水350 ml,以磷酸(1→10)调节pH至5.5]-甲醇(36:65)为流动相,流速:1.0 ml·min-1,检测波长284 nm.结果:兰索拉唑与杂质A、B、C、D、E的分离度均符合要求,系统适用性良好,兰索拉唑在0.303～2.725 μg范围内线性关系良好,方法平均回收率为99.8%(RSD=0.64%).结论:该法简便、准确,可用于注射用兰索拉唑的主药含量及有关物质测定.     

某综合医院门诊不合理用药处方分析

目的 对本院2010 -05 ～2011 -06门诊处方进行评价分析,了解本院门诊处方不合理用药情况.方法 随机抽取2010 -05～2011 -06门诊处方每月各100张,共计1400张,对其进行评价分析.结果 1400张处方中,不合理的处方479张,其中不规范处方320张,占不合理处方百分比的66.81％;用药不适宜处方157张,占不合理处方百分比的32.78％;超常处方2张,占不合理处方百分比的0.42％.结论 医师与药师应共同努力学习,提高专业知识水平,加强协作,才能更好地保障患者用药安全、有效、经济、合理.     

Treatment Implications of Predominant Polarity and the Polarity Index: A Comprehensive Review

Background:

Bipolar disorder (BD) is a serious and recurring condition that affects approximately 2.4% of the global population. About half of BD sufferers have an illness course characterized by either a manic or a depressive predominance. This predominant polarity in BD may be differentially associated with several clinical correlates. The concept of a polarity index (PI) has been recently proposed as an index of the antimanic versus antidepressive efficacy of various maintenance treatments for BD. Notwithstanding its potential clinical utility, predominant polarity was not included in the DSM-5 as a BD course specifier.

Methods:

Here we searched computerized databases for original clinical studies on the role of predominant polarity for selection of and response to pharmacological treatments for BD. Furthermore, we systematically searched the Pubmed database for maintenance randomized controlled trials (RCTs) for BD to determine the PI of the various pharmacological agents for BD.

Results:

We found support from naturalistic studies that bipolar patients with a predominantly depressive polarity are more likely to be treated with an antidepressive stabilization package, while BD patients with a manic-predominant polarity are more frequently treated with an antimanic stabilization package. Furthermore, predominantly manic BD patients received therapeutic regimens with a higher mean PI. The calculated PI varied from 0.4 (for lamotrigine) to 12.1 (for aripiprazole).

Conclusions:

This review supports the clinical relevance of predominant polarity as a course specifier for BD. Future studies should investigate the role of baseline, predominant polarity as an outcome predictor of BD maintenance RCTs.     

Candidal Urinary Tract Infections: A Comprehensive Review of Their Diagnosis and Management

Despite its prevalence, the significance of candiduria remains uncertain. The pathogenesis of candidal urinary tract infections has been relatively well characterized and many risk factors have been identified. The disorders lack consistent diagnostic criteria, however, such as the presence of pyuria or a colony count above which is predicative of presence, location, or severity of infection. Treatment is unclear due to lack of data defining the natural progression of the disease. Although often recommended, it may not always be possible to remove risk factors. Amphotericin B, fluconazole, 5-flucytosine, and other antifungal agents are important agents for managing candidal urinary tract infections.     

兰索拉唑的合成工艺研究

兰索拉唑是新型质子泵抑制剂,它是奥美拉唑开发后的第二个新型质子泵抑制剂,对基础胃酸分泌和由组胺、五肽胃泌素、二丁基环腺酸、胆碱及食物等引起的胃酸形成与分泌有强力持久的抑制作用,同时对胃肠黏膜有保护作用。为了开发研究此产品,对其合成工艺进行了研究,同时对文献工艺进行了改进,提高了收率,降低了成本,使其更适合工业化的要求.     

Lansoprazole: pharmacokinetics,pharmacodynamics and clinical uses

Lansoprazole (Prevacid?, TAP Pharmaceuticals, Inc.) is a substituted benzimidazole that inhibits gastric acid secretion. This agent is approved for the short-term treatment of erosive reflux oesophagitis, active gastric ulcer, active duodenal ulcer and the treatment of non-steroidal anti-inflammatory drug (NSAID)-induced gastric and duodenal ulcers. It is also approved for the long-term treatment of healed reflux oesophagitis, healed duodenal ulcer, the treatment of hypersecretory conditions such as Zollinger-Ellison syndrome and the eradication of Helicobacter pylori as a component of triple therapy with lansoprazole, clarithromycin and amoxicillin, or dual therapy with lansoprazole and amoxicillin. Its mechanism of action is to selectively inhibit the membrane enzyme H⁺/K⁺ATPase in gastric parietal cells. In clinical trials, lansoprazole is more effective than placebo or histamine (H₂)-receptor antagonists in the treatment of reflux oesophagitis. Lansoprazole administered at a dose of 30 mg daily produced faster relief of symptoms and superior healing rates in patients with gastric or duodenal ulcers or reflux oesophagitis than H₂-receptor antagonists. A daily dose of 30 mg lansoprazole reduced epigastric pain faster than omeprazole 20 mg daily in patients with peptic ulcer disease but healing rates at 4 and 8 weeks were similar with both agents at these dosages. Lansoprazole was more effective than H₂-receptor antagonists in patients with Zollinger-Ellison syndrome and produced similar treatment outcome to omeprazole. Lansoprazole in combination with clarithromycin and amoxicillin produced similar rates of eradication of H. pylori. In clinical trials, lansoprazole is well-tolerated and has a low frequency of side effects similar to that of H₂-receptor antagonists or omeprazole.     

Lansoprazole: pharmacokinetics, pharmacodynamics and clinical uses

Lansoprazole (Prevacid, TAP Pharmaceuticals, Inc.) is a substituted benzimidazole that inhibits gastric acid secretion. This agent is approved for the short-term treatment of erosive reflux oesophagitis, active gastric ulcer, active duodenal ulcer and the treatment of non-steroidal anti-inflammatory drug (NSAID)-induced gastric and duodenal ulcers. It is also approved for the long-term treatment of healed reflux oesophagitis, healed duodenal ulcer, the treatment of hypersecretory conditions such as Zollinger-Ellison syndrome and the eradication of Helicobacter pylori as a component of triple therapy with lansoprazole, clarithromycin and amoxicillin, or dual therapy with lansoprazole and amoxicillin. Its mechanism of action is to selectively inhibit the membrane enzyme H+/K+ ATPase in gastric parietal cells. In clinical trials, lansoprazole is more effective than placebo or histamine (H2)-receptor antagonists in the treatment of reflux oesophagitis. Lansoprazole administered at a dose of 30 mg daily produced faster relief of symptoms and superior healing rates in patients with gastric or duodenal ulcers or reflux oesophagitis than H2-receptor antagonists. A daily dose of 30 mg lansoprazole reduced epigastric pain faster than omeprazole 20 mg daily in patients with peptic ulcer disease but healing rates at 4 and 8 weeks were similar with both agents at these dosages. Lansoprazole was more effective than H2-receptor antagonists in patients with Zollinger-Ellison syndrome and produced similar treatment outcome to omeprazole. Lansoprazole in combination with clarithromycin and amoxicillin produced similar rates of eradication of H. pylori. In clinical trials, lansoprazole is well-tolerated and has a low frequency of side effects similar to that of H2-receptor antagonists or omeprazole.     

兰索拉唑的合成

目的 改进兰索拉唑的合成方法。方法通过改变文献合成中间体及兰索拉唑粗品过程中所用溶剂,改用乙醇、乙酸 乙酯为溶剂,提高产物的收率及合成的安全性。结果与结论 新合成方法使纯品产率稳定在89．5％,优于文献报道的方法。     

The Role of Levomilnacipran in the Management of Major Depressive Disorder: A Comprehensive Review

Levomilnacipran, the more active enantiomer of the serotonin and norepinephrine reuptake inhibitor (SNRI) milnacipran, was recently approved in the US for the treatment of major depressive disorder (MDD). The drug was developed as an extended release (ER) capsule formulation to allow for once-daily administration, thereby improving patient adherence. This agent differs from other available SNRIs in having a greater potency for inhibition of norepinephrine relative to serotonin reuptake. The efficacy of levomilnacipran ER has been evaluated in seven randomised, double-blind clinical trials (one Phase II and four Phase III trials, and two long-term efficacy studies). These studies documented that levomilnacipran is generally more effective than placebo for the treatment of MDD in the short-term, whereas no firm evidence exists on long-term efficacy for relapse prevention. Preliminary evidence suggests that levomilnacipran ER may be effective in improving not only depressive symptoms but also symptoms related to functioning (social life, work, and family life). Short-and longer-term studies found that the rate of withdrawal from levomilnacipran therapy due to adverse events was rather low. Moreover the drug appeared to be generally well tolerated. The most common adverse effects included nausea, hyperhidrosis, constipation, tachycardia, palpitations, erectile dysfunction and ejaculation disorder. As hypertension or orthostatic hypotension may occur in a few patients, the cardiovascular safety of levomilnacipran needs to be more extensively investigated especially on long-term treatment. Additional active comparator trials evaluating efficacy, tolerability and cost-effectiveness are required to better define the role of levomilnacipran ER in the treatment of MDD in relation to currently available antidepressants including other SNRIs.     

Sample Size Determinations for the Wilcoxon–Mann–Whitney Test: A Comprehensive Review

The Wilcoxon–Mann–Whitney (WMW) test is the most commonly used nonparametric method to compare two treatments when the underlying distribution of the outcome variable is not normally distributed. The sample size calculation methods for the WMW test have been extensively discussed in the literature. In this article we give a comprehensive review of sample size calculation methods for the WMW test on data with or without ties. We also provide detailed implementation of these sample size calculation methods for the WMW test depending on the characteristics of the data and the amount of available information. In addition, the implementation of these methods in popular sample size calculation software packages is also discussed. This article will be very helpful for researchers to determine sample sizes for the WMW test in the design phase of a study.     

兰索拉唑合成路线图解

兰索拉唑(1ansoprazole,1),化学名为2-[[[3-甲基-4-(2,2,2-三氟乙氧基)-2-吡啶基]甲基]亚磺酰基]-1H-苯并咪唑,是由日本武田公司开发的H /K-ATP酶抑制剂,于1991年首次在法国上市,用于食管炎和十二指肠溃疡的短期治疗[1,2].与奥美拉唑(omeprazole)相比,由于1的吡啶环4-位引入了三氟乙氧基,使得1具有更好的疗效、较少的副作用和更强的稳定性[3].     

Pharmacokinetics:Pharmacokinetic Differences Between Lansoprazole Enantiomers in Rats

Because limited information is available about potential differences between the pharmacokinetics and pharmacodynamics of the enantiomers of lansoprazole, the enantioselective pharmacokinetics of the compound have been investigated in rats. There was a noticeable difference between the serum levels of the enantiomers of lansoprazole and of their metabolites, 5-hydroxylansoprazole enantiomers, after oral administration of the racemate (50 mg kg^?1) to rats. C_max (maximum serum concentration) and AUC (area under the serum concentration-time curve) for (+)-lansoprazole were 5–6 times greater than those for (—)-lansoprazole, whereas for (+)-5-hydroxylansoprazole both values were significantly smaller than those for the (—) enantiomer. CL_tot/F values (where CL_tot is total clearance and F is the fraction of the dose absorbed) for (+)-lansoprazole were significantly smaller than those for the (—) enantiomer. There was no significant difference between the absorption rate constants of the lansoprazole enantiomers in the in-situ absorption study. The in-vitro protein-binding study showed that binding of (+)-lansoprazole to rat serum proteins was significantly greater than for the (—) enantiomer. The in-vitro metabolic study showed that the mean metabolic ratio (45.9%) for (—)-lansoprazole was significantly greater than that (19.8%) for the (+) enantiomer in rat liver microsomes at 5.6 μM lansoprazole. These results show that the enantioselective disposition of lansoprazole could be a consequence of the enantioselectivity of plasma-protein binding and the hepatic metabolism of the enantiomers.     

Lansoprazole versus omeprazole: influence on meal-stimulated gastric acid secretion

Aims: To investigate, by means of meal-stimulated acid secretion, the extent to which differences in plasma half-life, bioavailability and the recommended therapeutic dose can influence the antisecretory potency of lansoprazole and omeprazole.
Methods: In this double-blind, placebo-controlled, crossover study, 10 healthy male volunteers received 15 mg or 30 mg lansoprazole, 20 mg or 40 mg omeprazole or placebo for 5 days, in a randomized order. Meal-stimulated acid secretion was determined by means of a homogenized test meal and intragastric titration.
Results: On day 1, meal-stimulated acid secretion was decreased by 35% and 45% after administration of 15 mg or 30 mg lansoprazole, and by 16% and 42% after 20 mg or 40 mg omeprazole. After 3 and 5 days of dosing the decreases were 53% and 48% with 15 mg lansoprazole, 82% and 82% with 30 mg lansoprazole, 43% and 39% with 20 mg omeprazole, and 76% and 83% with 40 mg omeprazole. At all measuring points during the 5-day dosing periods, lansoprazole 15 mg and 30 mg proved superior to 20 mg omeprazole in inhibiting meal-stimulated gastric acid secretion, but the differences were only statistically significant for the lansoprazole 30 mg dose. 30 mg lansoprazole and 40 mg omeprazole proved equipotent. On day 1 only 30 mg lansoprazole was significantly better than placebo.
Conclusion: This study demonstrated the following order of antisecretory potency: 30 mg lansoprazole=40 mg omeprazole>15 mg lansoprazole≈20 mg omeprazole.