两种质子泵抑制剂治疗幽门螺杆菌阴性胃溃疡的药物经济学评价

目的：应用药物经济学原理分析奥美拉唑与兰索拉唑治疗幽门螺旋杆菌（ Hp ）阴性胃溃疡成本－效果,为合理用药提供科学依据。方法：选择符合标准的患者87例,分为奥美拉唑组44例和兰索拉唑组43例,疗程结束时评价临床效果及成本－效果。结果：奥美拉唑组患者治愈23例、显效9例、有效5例、无效7例,总有效率84．09％;兰索拉唑组患者治愈24例、显效10例、有效4例、无效5例,总有效率88．37％,差异无统计学意义（χ2＝0．335,P＝0．563）。奥美拉唑组C／E为0．46,低于兰索拉唑组的1．99,△C／△E为89．65,差异具有统计学意义（ P＜0．05）。敏感度分析示奥美拉唑组C／／E为0．41,低于兰索拉唑组的1．79,ΔC／／ΔE为89．45,差异具有统计学意义（ P＜0．05）。奥美拉唑组不良反应发生率4．55％,与兰索拉唑组6．98％相似,差异无统计学意义（ P＞0．05）。结论：奥美拉唑治疗Hp阴性胃溃疡具有更高的药物经济学价值,可减少医疗资源浪费。     

铝碳酸镁联合兰索拉唑治疗幽门螺旋杆菌相关性胃溃疡的临床疗效及安全性

目的探究铝碳酸镁联合兰索拉唑在治疗幽门螺旋杆菌相关性胃溃疡中的临床疗效及安全性。方法从2012年9月至2014年2月接诊的幽门螺旋杆菌相关性胃溃疡病例中随机选取符合条件的病例80例作为研究对象,按照入院治疗的先后顺序分为治疗组和对照组。两组均给予三联疗法进行幽门螺杆菌(Hp)的根除治疗,对照组再服用兰索拉唑,治疗组在对照组的基础上加服铝碳酸镁。经过8周的治疗后,观察两组病例溃疡的临床疗效、幽门螺旋杆菌根除情况、不良反应以及复发情况。在治疗过后4个月对两组病例进行胃镜复查,观察两组病例的复发情况。结果经过8周的治疗,治疗组的总有效率95.0%明显高于对照组(67.5%);治疗组的幽门螺旋杆菌根除率82.5%高于对照组(60.0%),差异具有统计学意义(P0.05)。两组不良反应发生情况差异无统计学意义。治疗4个月后进行复查,治疗组出现复发症状的几率明显低于对照组,差异具有统计学意义(P0.05)。结论铝碳酸镁联合兰索拉唑对幽门螺旋杆菌相关性胃溃疡具有良好的治疗效果,提高溃疡的愈合质量,降低溃疡复发率,不良反应较少,是一种安全有效的治疗手段,值得在临床治疗中推广应用。     

铝镁加联合兰索拉唑防治重型颅脑损伤应激性溃疡的临床疗效观察

目的研究铝镁加联合兰索拉唑在重型颅脑损伤并发应激性溃疡中的预防和治疗效果及相关的发病机理．为提高患者的治愈率提供依据。方法选择我院2009年5月～2012年8月入院接受治疗的90例重型颅脑损伤的患者作为研究对象,按照随机分组原则将所有患者分为铝镁加联合兰索拉唑组（治疗组）45例与兰索拉唑组（对照组）45例,人院后两组均积极接受颅脑外伤对症处理包括开颅手术,脱水,激素,冬眠低温等治疗,并每日给予兰索拉唑静脉滴注,治疗组在上述基础上给予预防性应用铝镁加混悬液,由胃管注入,每日3次。两组均治疗1个疗程即4周后,比较两组患者治疗前后神经损害严重程度（NNS）评分、格拉斯哥昏迷量表（GCS）评分以及应激性溃疡发生率。结果两组治疗前NNS、GCS评分结果差异无统计学意义,治疗1个疗程后,治疗组的NNS、GCS水平明显高于对照组,且治疗组的应激性溃疡发生率明显低于对照组,组间差异明显（P〈0．05）。结论对于重型颅脑损伤患者使用铝镁加联合兰索拉唑,对损伤后应激性溃疡具有较强的预防性作用,同时对颅脑损伤患者短期内行为学评价及神经功能评价具有明显改善,值得临床进一步推广使用。     

The Introduction of H2-Receptor Antagonists to Scandinavia: Effects of Experts' Opinions

To evaluate the therapeutic potential of the newly developed proton pump inhibitor lansoprazole in patients with reflux oesophagitis, we performed a double-blind randomized clinical trial comparing 20 mg omeprazole and 30 mg lansoprazole, involving 229 patients at 9 Scandinavian hospitals. The treatment period was 4 or 8 weeks, and main efficacy variables were healing of endoscopic changes, relief of reflux symptoms, and occurrence of adverse events. No significant difference in terms of healing was found, either after 4 or after 8 weeks' treatment. Patients receiving lansoprazole experienced a greater improvement in heartburn after 4 weeks (p = 0.03), and there was a similar trend for acid regurgitation. Lansoprazole was found to be an effective and safe alternative to omeprazole in short-term treatment of moderate reflux oesophagitis.     

Optimization of melt pelletization in a high shear mixer

The effects of process conditions and binder content on the process yield and pellet characteristics of two formulations prepared by melt pelletization in a laboratory-type high shear mixer were investigated. The formulations were prepared using Gelucire^® 50/13 and Lutrol^® F68 as meltable binders. The factors under investigation were impeller speed, mixing time, mixer load, binder concentration, and their reciprocal interactions. Analysis of variance (ANOVA) was used in order to study the significance of above mentioned process variables on the useful yield. Twenty-seven experiments were required for the response surface methodology based on Box–Behnken experimental design (24 combinations with three replications of the centre point) for each formulation.The control over the process and the quality of the resulting pellets were found to depend on the rheological properties of the binders used. In the case of a low viscosity binder (Gelucire^® 50/13), the process was easily controllable whereas in the case of a high viscosity binder (Lutrol^® F68), the process was more difficult to control.The useful yield of the formulation in the case of the low viscosity binder was found to be mostly influenced by the concentration of the binder. On the other hand, different binder concentrations did not affect the useful yield of the formulation prepared by use of the high viscosity binder. In the latter case, mixing time was identified as the variable that mostly influenced the pelletization process.Finally response surface methodology was applied to find the optimum values of the process variables.     

CYP2C19 genotype is associated with symptomatic recurrence of GERD during maintenance therapy with low-dose lansoprazole

Background/aims  Maintenance therapy of gastroesophageal reflux disease (GERD) is usually performed with a low dose of a proton-pump inhibitor (PPI). Because PPIs are metabolized by CYP2C19 in the liver, we investigated whether a patient’s CYP2C19 genotype was associated with symptomatic recurrence of GERD during maintenance therapy with a low dose of a PPI. Methods  We enrolled 124 patients with erosive GERD whose esophageal mucosal breaks were endoscopically proven to be cured after treatment with lansoprazole 30 mg/day for 8 weeks. When reflux symptoms occurred less than once per week, the dose of lansoprazole was decreased to 15 mg/day, but if symptoms then occurred more than once per week, it was restored to 30 mg/day. CYP2C19 genotypes were classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). Results  In 18 of 54 RMs, 28 of 56 IMs, and 8 of 14 PMs, the maintenance dose of lansoprazole was decreased to 15 mg/day, but in 16 (88.9%), 22 (78.6%), and 4 (50%), respectively, there was symptomatic recurrence of GERD and the dose was restored to 30 mg/day. The hazard ratios of symptomatic recurrence of GERD in IMs and PMs compared with RMs were 0.40 (95%CI: 0.19–0.87, P = 0.021) and 0.19 (95%CI: 0.05–0.69, P = 0.011). Conclusion  When the dose of lansoprazole is decreased, the RM genotype of CYP2C19 appears to be a risk factor for symptomatic recurrence of GERD. The CYP2C19 genotyping test would be useful for determining the optimal dose of a PPI for maintenance therapy of GERD. The abstract of the present study was presented at the annual meeting of the AGA held in San Diego, CA, in 2008.     

RP-HPLC法测定兰索拉唑的血药浓度

目的建立测定家兔血清中兰索拉唑浓度的反相高效液相色谱法。方法色谱柱为AT.ChromC18(250mm×4.6mm,5μm);流动相为乙腈-水-三乙胺(380:620:1),用磷酸调节PH=7,流速为1.0mL/min;检测波长为285nm;柱温为40℃。结果兰索拉唑的线性范围为0.05μg/mL-5.0μg/mL,回归方程为Y=8486.8X+414.64(r=0.9974),最低检测浓度为0.01μg/mL。结论本方法操作简便快速,提取量效突出,测定结果准确,检测限浓度低,重现性好,可以用于兰索拉唑的动力学研究。     

兰索拉唑三联疗法根除幽门螺杆菌的成本-效果分析

目的：对3种兰索拉唑三联疗法治疗幽门螺杆菌感染的方案进行经济学评价。方法：将85例经胃镜确诊为胃或十二指肠溃疡伴Hp阳性患者随机分为3组。LCA组,口服阿莫西林胶囊（A）1.0g,bid;LCF组,口服呋喃唑酮片（F）0.2g,bid;LCZ组,口服左氧氟沙星胶囊（Z）0.2g,bid,并且3组同时口服兰索拉唑（L）30mg,bid,克拉霉素颗粒剂（C）500mg,bid,疗程均为7日。三联治疗结束后再分别予以兰索拉唑30mg,qd,整个疗程为3周,采用药物经济学的成本-效果法进行分析。结果：3组Hp根除率和溃疡愈合率差异无显著性,但治疗成本不同。结论：LCF三联疗法成本最低,并且效果最好。     

高效液相色谱-质谱联用法测定人血浆中兰索拉唑的浓度

目的：建立高效液相色谱-质谱联用法测定人血浆中兰索拉唑的浓度。方法：血浆样品经处理后。采用WatersAdan—tis C18色谱柱（100mm×2．1mm,3μm）,流动相为甲醇-0．01％甲酸溶液（70：30）,以电喷雾电离源（ESI）正离子检测,奥美拉唑为内标。结果：兰索拉唑血浆质量浓度的线性范围为5．0～1500．0ng·ml-1（r=0．9998）,,提取回收率为78．2％。88．9％（n=5）,方法回收率为90．3％～101.9％（n=5）,日内和日间RSD均小于10％。结论：本法专属性强,样品处理方便,灵敏度高,适用于兰索拉唑药动学研究。     

Improvement in symptoms after H2-receptor antagonist-based therapy for eradication of H pylori infection

AIM： To investigate the therapeutic effects of triple therapy combining lafutidine with clarithromycin and amoxicillin on H pylori infection and the resolution of gastroesophageal symptoms after eradication.
METHODS： We conducted a randomized, multicenter, open-label controlled trial to compare the effectiveness of a triple therapy of lafutidine, clarithromycin, and amoxicillin （lafutidine group） with that of a triple therapy of lansoprazole, clarithromycin, and amoxicillin （lansoprazole group） in patients with Hpylori infection. The study group comprised 22 patients with gastric ulcers and 18 patients with duodenal ulcers who had Hpylori infection.
RESULTS： H pylori eradication rates were similar in the lafutidine group （14/20, 70%） and the lansoprazole group （14/20, 70%）. Gastroesophageal reflux and ab- dominal symptoms improved after eradication therapy in both groups, whereas abdominal discomfort, diarrhea, and constipation were unchanged. H pylori status had no apparent effect on improvement of gastroesophageal reflux or abdominal symptoms after treatment. Adverse events were similar in both groups.
CONCLUSION： The triple therapy including lafutidine is equivalent to triple therapy including lansoprazole in terms of H pylori eradication rates and improvement in gastroesophageal reflux and abdominal symptoms.These results are attributed to the fact that lafutidine has strong, continuous antisecretory activity, unaffected by CYP2C19 polymorphisms.