兰索拉唑中有机溶剂残留量的毛细管GC测定

建立了毛细管气相色谱法测定兰索拉唑中甲醇、丙酮、乙腈、氯仿的残留量.采用RTX-50毛细管柱,程序升温.各溶剂检测限分别为18、50.4、1.46和0.4ng,平均回收率分别为102.3%、100.4%、101.8%和1013%.     

Treatment of erosive reflux esophagitis resistant to H2-receptor antagonist therapy

Fifty-four patients with endoscopically documented therapy-resistant erosive reflux esophagitis were treated with lansoprazole, a new proton pump inhibitor, for up to 12 weeks. Prior to entry, all had remained unhealed after treatment with at least two histamine₂-receptor antagonists, at therapeutic doses or higher, for at least 12 weeks. Patients were randomized to receive either 30 or 60 mg lansoprazole once daily. Endoscopy was performed and symptoms assessed at weeks 2, 4, 6, 8, and 12. Fifty-nine percent of the 50 evaluable patients were healed (ie, no evidence of erosions) after only two weeks of lansoprazole. Cumulative endoscopic healing rates were 82% and 92% by week 4 and week 8, respectively, and the two doses were equally effective in healing. The 30- and 60-mg doses effected a decrease in the overall symptom score from 5.30 and 4.85 to 2.35 and 1.67, respectively, by the final treatment visit (P=0.001). No clinically significant adverse events or changes in laboratory parameters were observed, and no patients withdrew prematurely from the study. This study demonstrates that lansoprazole therapy is highly effective in healing erosive reflux esophagitis resistant to therapy with histamine H₂-receptor antagonists.Supported by a grant from TAP Pharmaceuticals Inc., Deerfield, Illinois.     

Effect of lansoprazole on DNA integrity of human spermatozoa and activity of seminal creatine kinase

Although lansoprazole (brand name Prevacid) is a commonly used dug to manage various acid-related gastrointestinal diseases, little is known about its effects on human semen quality and sperm parameters. Here, we aimed to investigate the effect of lansoprazole on DNA integrity of human spermatozoa and activity of seminal creatine kinase. DNA integrity of human spermatozoa was assessed by the Apo-Direct™ kit followed by flow cytometry. The activity of creatine kinase was measured by kinetic spectrophotometric method using commercially available kits following the International Federation of Clinical Chemistry recommendations. Lansoprazole at 3 µg/ml, after 1-hr incubation period, did not show any significant increase in fluorescein isothiocyanate fluorescence (p > .05) and hence on the content of DNA breaks of human spermatozoa. In addition, there was no significant change (p = .8113) in the activity of seminal creatine kinase by the effect of lansoprazole. In conclusion, lansoprazole at 3 µg/ml did not alter DNA integrity of human spermatozoa or activity of seminal creatine kinase after 1-hr incubation period.     

Influence of lansoprazole,famotidine, roxatidine and rebamipide administration on the urea breath test for the diagnosis of Helicobacter pylori infection

BACKGROUND AND AIM: The sensitivity of the urea breath test (UBT) has been reported to be influenced by the administration of omeprazole, lansoprazole and ranitidine. However, it is unclear whether other H2 receptor antagonists (H2RA), except ranitidine, and rebamipide, a mucosal protective agent, affect UBT sensitivity. The aim of this study is to clarify the effects of lansoprazole, famotidine, roxatidine and rebamipide administration on UBT sensitivity. METHODS: Subjects comprised 30 volunteers with Helicobacter pylori infection. All subjects were examined by the 13C-UBT on four occasions: (i) without medication (control); (ii) after the administration of 30 mg lansoprazole (u.i.d) for 14 days; (iii) after the administration of 100 mg rebamipide (t.i.d) for 14 days; and (iv) after the administration of 20 mg famotidine or 75 mg roxatidine (b.i.d) for 14 days. In the H2RA study, individuals were randomized into two groups of 15 subjects and were administered either famotidine or roxatidine. RESULTS: Five of the 30 cases administered lansoprazole and one of the 15 cases given roxatidine gave a false-negative UBT result. No negative UBT results were observed in patients administered famotidine or rebamipide. CONCLUSION: Patients showing negative UBT results during the administration of proton pump inhibitors and H2RA should be re-examined after the cessation of these drugs to confirm the true negativity of H. pylori infection.     

Colorectal cancer extracellular acidosis decreases immune cell killing and is partially ameliorated by pH-modulating agents that modify tumor cell cytokine profiles

Tumor cells upregulate myriad proteins that are important for pH regulation, resulting in the acidification of the extracellular tumor microenvironment (TME). Abnormal pH is known to dampen immune function, resulting in a worsened anti-tumor immune response. Understanding how extrinsic alterations in pH modulate the interactions between immune cells and tumors cells will help elucidate opportunities for new therapeutic approaches. We observed that pH impacts the function of immune cells, both natural killer (NK) and T cells, which is relevant in the context of a highly acidic TME. Decreased NK and T cell activity was correlated with decreasing pH in a co-culture immune cell-mediated tumor cell-killing assay. The addition of pH-modulating drugs cariporide, lansoprazole, and acetazolamide to the co-culture assay was able to partially mitigate this dampened immune cell function. Treatment of colorectal cancer (CRC) cells with NHE1 inhibitor cariporide increased CRC cell-secreted cytokines involved in immune cell recruitment and activation and decreased cytokines involved in epithelial-mesenchymal transition (EMT). Cariporide treatment also decreased CRC cell shed TRAIL-R2, TRAIL-R3, and PD-L1 which is relevant in the context of immunotherapy. These experiments can help inform future investigations into how the pH of the tumor microenvironment may be extrinsically modulated to improve anti-tumor immune response in solid tumors such as colorectal cancer.     

Management of symptoms in step-down therapy of gastroesophageal reflux disease

OBJECTIVE: Majority of studies on gastroesophageal reflux disease (GERD) that include patients with or without erosive disease have documented the efficacy of proton pump inhibitors (PPIs) as well as their superiority to H(2)-receptor antagonist (H(2)-RA). The purpose of this study was to clarify the difference in quality of GERD treatment with PPIs and H(2)-RA in step-down protocol using lansoprazole. METHODS: Forty-three patients with reflux esophagitis were randomly divided into three groups and assessed by severity score; group 1 received 30 mg lansoprazole initially and maintenance therapy with a standard dose H(2)-RA; group 2 received 30 mg of lansoprazole initially and maintenance therapy of 15 mg lansoprazole; and group 3 received 15 mg of lansoprazole once daily for 16 weeks. If the patients experienced symptomatic recurrence while on H(2)-RA, they were switched to PPI maintenance. RESULTS: Heartburn, regurgitation and dysphagia were hardly found in any group at 8 weeks after 15 mg or 30 mg lansoprazole treatment. After 8 weeks, however, heartburn and regurgitation recurred at 50% and 78.6%, respectively, in the stepped down to famotidine group, and quality of life (QOL) was significantly impaired. Endoscopic ultrasonography (EUS) analysis showed reduction of the submucosal layer without any change in the mucosal surface in the stepped down to famotidine group. CONCLUSIONS: Step-down lansoprazole therapy is considered very effective in terms of rapid effect, long-term effect and high quality GERD treatment.     

泮托拉唑与兰索拉唑治疗胃溃疡的药物经济学分析

目的评价泮托拉唑与兰索拉唑治疗胃溃疡的药物经济学效果。方法选取本院2010年7月—2012年7月消化内科收治的胃溃疡患者83例,采用随机数字表法分为观察组(n=43)和对照组(n=40),分别给予泮托拉唑和兰索拉唑治疗。比较2组患者临床改善总有效率、不良反应发生率、总治疗费用、成本-效果等指标。结果观察组与对照组临床改善总有效率分别为93.03%和95.00%,不良反应发生率分别为27.91%和27.50%,2组患者临床改善总有效率及不良反应发生率比较差异均无统计学意义(P>0.05);观察组与对照组成本-效果指标分别为4.99和5.57;与观察组相比,对照组治疗成本更高。结论在胃溃疡治疗中,泮托拉唑方案的药物经济学价值高于兰索拉唑方案。     

注射用兰索拉唑与常用输液的配伍稳定性

目的：研究注射用兰索拉唑与4种常用输液配伍的稳定性。方法：采用HPLC法考察与4种输液按临床应用配伍，干室温条件下，考察12h内pH值，外观和含量的变化情况。结果：在室温条件下，与生理氯化钠溶液配伍后，6h内基本稳定，与10％葡萄糖，5％葡萄糖氯化钠和5％葡萄糖配伍后，随时间延长，含量分别降至97．5％，97．6％．98．0％。结论：注射用兰索拉唑可与生理氯化钠溶液配伍使用，但是应在4h内用完。     

HPLC测定注射用兰索拉唑中兰索拉唑的含量和有关物质

 目的采用高效液相色谱法建立注射用兰索拉唑有关物质检查及其含量测定方法。方法Diamonsil-C₁₈柱(4.6 mm×200 mm,5μm),以甲醇-水-三乙胺-磷酸(640∶360∶5∶1.5,pH为7.3)为流动相,检测波长为284 nm。结果制剂中辅料对主药测定无干扰,兰索拉唑与有关物质完全分离。在10.0～400.0 mg·L^-1内峰面积与浓度呈良好的线性关系。精密度(RSD=0.13%)良好。平均回收率为99.6%。结论本方法简便,迅速,准确,专属性强。