Evolving pharmacological approaches in gastroesophageal reflux disease

Introduction: Proton pump inhibitors (PPIs) have considerably improved quality of life in patients with gastroesophageal reflux disease (GERD). However, many patients remain symptomatic despite standard PPI therapy.

Areas covered: This review focuses on evolving therapeutic strategies related to the pathophysiological processes of GERD and insufficient response to PPIs. Several clinical trials evaluated new PPI formulations and newer types of acid-suppressive drugs. These studies have evaluated traditional end points in GERD, but have not shown clinical superiority to current PPIs. Novel therapeutic strategies targeting underlying mechanisms of GERD, such as transient lower esophageal sphincter relaxations (TLESRs) and esophageal hypersensitivity, are being developed for add-on therapy to PPIs. Prokinetic drugs may also have some potential in the add-on treatment of GERD with insufficient response to PPIs. Add-on studies are hampered by insufficient information on optimal patient selection and lack of established end points.

Expert opinion: Newer drugs for symptomatic control in GERD have largely focused on improved acid suppression, without evidence of clinical superiority. Drugs targeting esophageal motility and sensitivity to be used as add-onc therapy in PPI insufficient responders have not reached Phase III trials to date, due to difficulties with patient selection, tolerability and end points.     

右兰索拉唑的合成工艺研究

目的 对右兰索拉唑的合成工艺进行研究。方法 以4-氯-2,3-二甲基吡啶-N-氧化物为起始原料,经酰化、水解、氯代、取代反应得到兰索拉唑硫醚,再进行不对称氧化、取代反应获得右兰索拉唑。结果 合成右兰索拉唑对映体过量值（ee值）为99.5%,总收率为21.6%。结论 改进后的工艺成本低、操作方法简单、后处理容易、收率高、产物纯度高、可用于工业放大生产。     

右兰索拉唑缓释胶囊健康人体生物等效性及安全性评价

目的:评价右兰索拉唑缓释胶囊在健康受试者空腹、餐后状态下的人体生物等效性及安全性.方法:采取随机、开放、四周期、两交叉单次给药设计,空腹组及餐后组各有30例健康受试者入选,采用高效液相色谱,串联质谱法测定受试者每周期口服右兰索拉唑缓释胶囊受试制剂或参比制剂(Dexilant(R))后15个不同时间点的右兰索拉唑浓度.采...     

右旋兰索拉唑的药理学特点及在胃食管反流病治疗中的应用

虽然质子泵抑制剂(PPI)在胃食管反流病(GERD)治疗方面取得了很大的成功,但是抑酸时间不足、患者依从性差等挑战仍然存在。近期,美国FDA批准了一种新的PPI药物右旋兰索拉唑(dexlanso-prazole,日本武田公司开发,商品名:DexliantTM),目前主要用于糜烂性食管炎急性期及维持期的治疗,以及非糜烂性胃食管反流疾病烧心症状的控制。该药物采用独特的双层缓释技术,可以维持更长的作用时间,达到更好的抑酸效果,且安全性和耐受性良好。     

右旋兰索拉唑双相释放胶囊在Beagle犬体内的药动学研究

建立了LC-MS/MS法测定犬血浆中的右旋兰索拉唑,并研究了右旋兰索拉唑控释胶囊(商品名:Dexilant)在Beagle犬体内的药动学.采用C18柱,以甲醇-水(含10 mmol/L甲酸铵,70:30)为流动相,奥美拉唑为内标.右旋兰索拉唑在5～2 000 ng/ml浓度范围内线性关系良好,提取回收率105.7％～123.1％,批内、批间RSD均小于10％.Beagle犬口服给药后,呈明显血药双峰现象,药动学参数t1/2为(0.6±0.1)h,AUC0-∞为(2 019±176) ng·ml-1h,cmax为(810.9±194.0) ng/ml.     

Dexlansoprazole MR for the management of gastroesophageal reflux disease

Dexlansoprazole modified release (MR; Dexilant?), the R-enantiomer of lansoprazole, was approved in the USA in 2009 for the management of erosive esophagitis and nonerosive reflux disease. Dexlansoprazole MR has a unique dual delayed-release delivery system that was designed to address unmet needs that may accompany the use of single-release proton pump inhibitors (PPIs), specifically, their short plasma half-life and requirement for meal-associated dosing. The delivery technology of dexlansoprazole MR is designed to release the drug in two separate pH-dependent phases, the first in the proximal duodenum and the second in the more distal small intestine. This extends plasma concentration and pharmacodynamic effects of dexlansoprazole MR beyond those of single-release PPIs and allows for dosing at any time of the day without regard to meals. This added convenience, along with excellent healing of esophagitis and symptom relief, substantiate its use in patients with gastroesophageal reflux disease requiring PPI treatment.     

用于胃食管反流症状的药物右兰索拉唑

反酸为一种常见症状，是指胃内容物经食管反流达口咽部，口腔感觉到酸性物质的现象。其与十二指肠内容物经胃、食管反流达口咽部，口腔感觉到出现苦味物质的现象，统称为反流。若每周持续反流2次以上则可被诊断为胃食管反流病（GERD）。     

High Efficacy of Levofloxacin-Dexlansoprazole-Based Quadruple Therapy as a First Line Treatment for Helicobacter pylori Eradication in Thailand

Background: Levofloxacin is an effective medication for second line Helicobacter pylori (H. pylori) eradication.However, limited studies have approved its use as an effective antibiotic in first line therapy. Dexlansoprazole isa new PPI and lacks of evidence in support of a role in H. pylori eradication. This study was designed to evaluateefficacy of levofloxacin-dexlansoprazole-based quadruple therapy for H. pylori eradication in Thailand. Materialsand Methods: This prospective randomized control study was performed during June 2014 to December 2014.H. pylori infected gastritis patients were randomized to receive 7- or 14-day levofloxacin-dexlansoprazole basedon quadruple therapy (levofloxacin 500 mg OD, dexlansoprazole 60 mg bid, clarithromycin MR 1000 mg OD,bismuth subsalicylate 1048 mg bid). CYP2C19 genotyping and antibiotic susceptibility tests were conductedfor all patients. A 13C urea breath test was performed to confirm H. pylori eradication at least 4 weeks aftertreatment. Results: A total of 100 patients were enrolled, comprising 44 males and 56 females (mean age of 52.6years). Eradication rate by PP analysis was 85.7% (42/49) with the 7-day regimen and 98% (48/49) with the14-day regimen (85.7% vs 98%; p-value=0.059). ITT analysis was 84% and 96% with 7- and 14-day regimens,respectively (84% vs 96%; p-value=0.092). Antibiotic susceptibility testing demonstrated 35.1% resistance tometronidazole, 18.3% to clarithromycin, and 13.5% to levofloxacin. CYP2C19 genotyping revealed 54.1% RM,34.7% IM and 11.2% PM. The 14-day regimen provided 100% eradication in patients with clarithromycin or dualclarithromycin and metronidazole H. pylori resistant strains. Moreover, the eradication rate was 96.6% in patientswith CYP2C19 genotype RM. Conclusions: The 14-day levofloxacin-dexlansoprazole based quadruple therapyprovides high H. pylori eradication regardless of CYP2C19 genotype, clarithromycin or dual clarithromycinand metronidazole resistant strains. This regimen could be use as an alternative first line therapy for H. pylorieradication in Thailand.     

右兰索拉唑缓释胶囊在比格犬体内的药动学

目的：研究右兰索拉唑缓释胶囊在比格犬体内的药动学特征。方法：将6只比格犬随机分为2组,采用双周期双交叉给药方法,单次灌胃60 mg右兰索拉唑缓释胶囊受试制剂或参比制剂,LC-MS/MS法测定比格犬体内右兰索拉唑血药浓度,计算药动学参数并进行生物等效性评价。结果：单次灌胃受试制剂和参比制剂后,比格犬血浆中右兰索拉唑的t_1/2分别为（1.34±0.73）和（1.42±0.63） h,T_max分别为（5.7±0.52）和（5.8±1.17） h,C_max分别为（385.5±37.14）和（380.5±53.3） ng·mL^-1,AUC_0-t分别为（1 463.9±213.2）和（1 502.3±147.8） ng·h·mL^-1,AUC_0-∞分别为（1 476.4±215.7）和（1 514.3±149.5） ng·h·mL^-1。结论：右兰索拉唑缓释胶囊受试制剂与参比制剂在比格犬体内生物等效。