Incidence ofHelicobacter pylori infections and therapy for anastomotic ulcers and residual gastritis in patients with residual stomachs

Seventy-seven patients with the vestibular portion of their stomachs resected (residual stomach) due to ulcers or stomach cancers were included in this study. Fifty-five (71.4%) of these patients hadHelicobacter pylori infections.H. pylori was found in all patients with stomach cancer, esophageal cancer, or esophageal venous varicosity, and in 86.7% of patients with esophagitis, 78.6% with residual gastritis, 70.0% with anastomotic ulcers, and in 51.6% of patients with normal mucosa in their resected stomachs. The in vitro antibacterial activities of amoxicillin, erythromycin, clarithromycin, minocycline, nalidixic acid, ofloxacin, lansoprazole, and omeprazole were determined against 10 clinical isolates ofH. pylori. All agents except ofloxacin, nalidixic acid and omeprazole showed satisfactory bactericidal activities. The clinical and bacteriological efficacies of a combined treatment regimen with lansoprazole and clarithromycin were evaluated in 10 patients with anastomotic ulcers and 6 patients with residual stomach inflammation after informed consent. The clinical efficacy of this treatment in these 16 patients was excellent for 3 patients, good for 12 patients, and fair for the other patient. Collectively, the treatment was effective in 15/16 (93.8%) of patients. The bacteriological efficacy of this treatment regimen was evaluated in 14 patients, with no evidence ofH. pylori 13 (92.9%) patients.     

Lymphocytic Colitis Associated with Lansoprazole Treatment

Introduction: There have been several reported cases of lansoprazole-associated collagenous colitis (CC) reported in the literature but only 1 reported case of lansoprazole-associated lymphocytic colitis (LC) in the literature. Both CC and LC are considered inflammatory bowel diseases, but they are distinctly classified based on the condition of the colon, which is typically confirmed through biopsy.Case summaries: A 52-year-old white male (Patient 1), with a height of 178 cm and weight of 75 kg, presented to Gazi University Hospital, Ankara, Turkey, with a 3-month history of abdominal pain and nonbloody, watery diarrhea. The patient reported receiving PO lansoprazole 30 mg/d to treat heartburn ~1 week prior to the onset of diarrhea. The patient's medical history revealed that he did not have any preexisting conditions, other than gastroesophageal reflux disease (GERD) for which lansoprazole was prescribed. The medical history report also revealed that the patient was not receiving any concomitant medications or treatments at the time. A colon biopsy confirmed LC. Additionally, a 43-year-old white female (Patient 2), with a height of 168 cm and weight of 61 kg, presented to the same facility with a 6-month history of nonbloody, watery diarrhea and mild lower abdominal cramping. The patient reported that initial onset began ~2 months after receiving a 10-day Helicobacter pylori eradication combination treatment regimen that included lansoprazole, amoxicillin, and clarithromycin, followed by lansoprazole monotherapy to treat GERD. The patient's medical history revealed no other concomitant medications were being adminstered at the time. A colon biopsy confirmed LC.Discussion: A search of the literature using the MEDLINE database and all relevant English-language articles with key words lansoprazole and lymphocytic colitis, found that there were several cases of lansoprazole-associated CC reported and 1 reported case of lansoprazole-associated LC. Histologic findings from laboratory tests and colon biopsies confirmed diagnoses of LC in both patients in this case report. Patient 1 presented with diarrhea and cramping, which the patient reported had been ongoing for ~3 months, following lansoprazole administration. However, after lansoprazole was discontinued, the symptoms completely resolved within 7 days. Patient 2 presented with diarrhea and cramping, which had been occurring for ~6 months. That patient reported that initial onset commenced ~2 months after a 10-day H pylori eradication combination treatment regimen that included lansoprazole, amoxicillin, and clarithromycin, followed by lansoprazole monotherapy to treat GERD. However, after sulfasalazine (3 g/d) was prescribed for 2 months immediately upon diagnosis of LC, there was little improvement in the effort to control the diarrhea in this patient. After omeprazole 20 mg/d was substituted for lansoprazole, the patient's diarrhea ceased. Follow-up sigmoidoscopy 2 months later revealed normal mucosa and complete normalization of histologic findings. The patient remains diarrhea-free while on omeprazole. A causality assessment using the Naranjo adverse reaction algorithm produced scores of 6 for both patients, suggesting that LC was probably associated with lansoprazole treatment.Conclusions: Here we report 2 cases of LC in patients probably associated with the administration of lansoprazole treatment. Complete remission occurred after lansoprazole was discontinued.     

液相色谱-串联质谱法测定人血浆中兰索拉唑及其代谢物浓度

目的建立液相色谱-串联质谱同时测定人血浆中兰索拉唑及其代谢物兰索拉唑砜、5-羟基兰索拉唑浓度的方法。方法用Agilent SB-C18色谱柱,流动相为0.002 mol.L-1乙酸铵(用甲酸调pH为4)-乙腈(60∶40,v/v),流速为0.3 mL.min-1。用正离子电离,多离子反应监测进行定量分析。结果兰索拉唑、兰索拉唑砜、5-羟基兰索拉唑线性范围分别为5～3044,1.5～550,2～549.5 ng.mL-1,三者日内、日间精密度均小于10%,三者的提取回收率为81.55%～98.74%(RSD<10%)。结论本方法灵敏、准确、快速,可用于人血浆中兰索拉唑及其代谢物浓度的测定和药代动力学研究。     

羟丙基-β-环糊精对兰索拉唑的增溶作用及其包合物的制备

目的研究羟丙基-β-环糊精(HP--βCD)对难溶性药物兰索拉唑(LPZ)的包合作用。方法绘制相溶解度图,考察pH变化、碳酸氢钠的加入对LPZ的增溶作用。采用共蒸发法(CE)和喷雾干燥法(SD)按照LPZ∶HP--βCD量比为1∶1或1.0∶1.5的比例制备LPZ/HP--βCD包合物,测定其溶出度,并利用差示扫描量热法(DSC)和傅立叶红外光谱法(FTIR)对SD法制备的包合物进行结构表征。结果在pH 11条件下,HP-β-CD与NaHCO3对LPZ的协同增溶效果最好。体外溶出实验表明:CE法和SD法制备的包合物溶出均优于LPZ与HP-β-CD的物理混合物。结论HP--βCD能明显提高LPZ的溶解度和溶出度。     

兰索拉唑分别与铝碳酸镁、莫沙比利合用的大鼠体内药动学研究

目的建立测定大鼠血浆中兰索拉唑的HPLC法,并比较兰索拉唑分别与铝碳酸镁、莫沙比利联合用药的大鼠体内药动学行为。方法18只健康雄性Wistar大鼠随机分为兰索拉唑组、兰索拉唑联合铝碳酸镁组和兰索拉唑联合莫沙比利组,灌胃给药。大鼠血浆样品经甲醇沉淀蛋白处理后进行药物浓度的测定。色谱柱为ODS-C18柱（150mm×4．6mm,5μm）;流动相：甲醇水（53：47）;检测波长：285nm。结果兰索拉唑在50～5000ng·mL^-1线性关系良好,方法回收率为84．0％～90．8％。3种给药方式兰索拉唑的主要药动学参数分别为：tmax：（0．28±0．04）、（2．17±0．26）和（0．28±0．12）h;Cmax：（1939±473．2）、（953±261．0）和（1889±721．9）ng·mL^-1;t1／2：（1．52±0．55）、（1．45±0．40）和（1．67±0．22）h;AUC0-10：（2559±519．5）、（3318±1082）和（3238±1514）ng·h·mL^-1;AUC0-∞：（2729±598．6）、（3498±1149）和（3438±1568）ng·h·mL^-1。经独立样本t检验及非参数检验分析,联用后,铝碳酸镁能明显推迟兰索拉唑达峰时间并降低峰浓度;莫沙比利对兰索拉唑的药动学行为没有显著影响。结论本方法专属性强、准确、简便,可为临床合理用药提供依据。     

兰索拉唑的合成工艺改进

目的 改进兰索拉唑的合成工艺。 方法 以2,3-二甲基吡啶为起始原料,经4步反应合成目标化合物。结果与结论 目标化合物的总收率由文献的12.7% 提高到21.2%,其结构经熔点、质谱和¹H-NMR谱测试确证。改进后的合成方法较原工艺路线缩短,易于工业化生产。     

Influence of rabeprazole and lansoprazole on the pharmacokinetics of tacrolimus in relation to CYP2C19, CYP3A5 and MDR1 polymorphisms in renal transplant recipients

The objective of this study was to evaluate whether genetic polymorphisms of CYP2C19, CYP3A5 and MDR1 significantly impact the interaction between tacrolimus and rabeprazole or lansoprazole. Seventy-three recipients were randomly assigned after renal transplantation to receive repeated doses of tacrolimus for 28 days with a regimen of either 20 mg of rabeprazole or 30 mg of lansoprazole. Blood concentrations of tacrolimus were measured by microparticle enzyme immunoassay. The mean daily dose and the dose-adjusted area under the plasma concentration-time curves from 0 to 12 h (AUC(0-12)) of tacrolimus coadministered with rabeprazole or lansoprazole were the lowest and highest, respectively, in CYP2C19 poor metabolizers (PMs) having the CYP3A5*3/*3 genotype (0.084 and 0.112 mg/kg/day and 1.269 and 1.033 ng.h/ml/mg/kg, respectively). On the other hand, the mean dose-adjusted AUC(0-12) of tacrolimus coadministered with rabeprazole or lansoprazole were the highest in CYP2C19 PMs having the MDR13435CC+CT genotype, but not significantly.The present study indicates that there are significant interactions between tacrolimus and rabeprazole or lansoprazole in CYP2C19 PM renal transplant recipients bearing the CYP3A5*3/*3 genotypes. For recipients having these genetic polymorphisms, lower dosages of tacrolimus are required to achieve the target therapeutic index.     

Effectiveness of Omeprazole- Versus Lansoprazole-Based Triple Therapy for <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Eradication

Triple therapy with a proton pump inhibitor (PPI), amoxicillin, and clarithromycin is widely accepted for Helicobacter pylori eradication. The choice of PPI for triple therapy in Israel is arbitrary, with no preference for any one PPI except for economic considerations. Direct comparison between omeprazole and lansoprazole for efficacy of H. pylori eradication has never been performed in an Israeli poplulation. Based on the pharmacokinetic data, lansoprazole-based therapy may be a better alternative than omeprazole-based therapy. The aim of this study was to compare the effectiveness of triple therapy regimens with omeprazole (Losec, AstraZeneca; or Omeradex, Dexxon) or lansoprazole (TAP Pharmaceuticals) in eradicating H. pylori infection. The database of the biggest health insurance provider in Israel was reviewed for all patients who received 1 week of treatment with omeprazole (n = 1293) or lansoprazole (n = 85) with additional amoxicillin and clarithromycin for H. pylori eradication in 2002. All patients underwent the ¹³C-urea breath test (¹³CUBT) for validation of eradication. A negative ¹³CUBT result was noted in 1026 of the patients treated with omeprazole (79.4%) and 61 treated with lansoprazole (71.8%). On logistic regression analysis, none of the confounding factors (sex, age, indication, chronic use of PPI, eradication protocol) were found to contribute to the discrimination between a negative (successful eradication) and a positive (failed eradication) ¹³CUBT. There is no statistically significant difference between omeprazole and lansoprazole as part of a PPI-based triple therapy for eradication of H. pylori.     

Influence of the proton pump inhibitor lansoprazole on distribution and activity of doxorubicin in solid tumors

Cellular causes of resistance and limited drug distribution within solid tumors limit therapeutic efficacy of anticancer drugs. Acidic endosomes in cancer cells mediate autophagy, which facilitates survival of stressed cells, and may contribute to drug resistance. Basic drugs (e.g. doxorubicin) are sequestered in acidic endosomes, thereby diverting drugs from their target DNA and decreasing penetration to distal cells. Proton pump inhibitors (PPIs) may raise endosomal pH, with potential to improve drug efficacy and distribution in solid tumors. We determined the effects of the PPI lansoprazole to modify the activity of doxorubicin. To gain insight into its mechanisms, we studied the effects of lansoprazole on endosomal pH, and on the spatial distribution of doxorubicin, and of biomarkers reflecting its activity, using in vitro and murine models. Lansoprazole showed concentration‐dependent effects to raise endosomal pH and to inhibit endosomal sequestration of doxorubicin in cultured tumor cells. Lansoprazole was not toxic to cancer cells but potentiated the cytotoxicity of doxorubicin and enhanced its penetration through multilayered cell cultures. In solid tumors, lansoprazole improved the distribution of doxorubicin but also increased expression of biomarkers of drug activity throughout the tumor. Combined treatment with lansoprazole and doxorubicin was more effective in delaying tumor growth as compared to either agent alone. Together, lansoprazole enhances the therapeutic effects of doxorubicin both by improving its distribution and increasing its activity in solid tumors. Use of PPIs to improve drug distribution and to inhibit autophagy represents a promising strategy to enhance the effectiveness of anticancer drugs in solid tumors.     

Symptomatic and endoscopic outcome of heartburn 3–4.5 years after starting lansoprazole therapy: a prospective study of 142 patients

Background Heartburn is a common symptom with great impact on quality of life and on the economy. An approach that helps to alleviate patients symptoms, decrease the burden on the economy, and improve longterm outcome is needed. Step-down therapy, starting with the proton pump inhibitor lansoprazole, seems to achieve these goals.Methods All patients who were referred to the gastroenterology clinic at the University Health Center to evaluate their heartburn and who met the inclusion criteria were included in the present study. Symptomatic and endoscopic evaluations were carried out and then they were started on the proton pump inhibitor lansoprazole to achieve symptomatic control. Step-down therapy was carried out for these patients, provided their symptoms remained controlled. At the end of the study symptomatic and endoscopic outcomes were evaluated.Results Heartburn was controlled on lansoprazole 30mg/per day in 76.1% of patients, and 18.3% required double this dose. Initial endoscopy showed normal findings in 38.7%, while 61.3% showed various grades of esophagitis including 1.4% with Barretts epithelium. Of 119 patients who completed the study, 17 were non-compliant to therapy, 52 were controlled on minimal therapy, 42 required lansoprazole to be kept symptom-free, and 8 patients had surgery. Endoscopic esophagitis was healed or attenuated in all compliant patients. No new cases of Barretts appeared during follow up.Conclusions Most of the patients with heartburn can be controlled on proton pump inhibitors, with improvement in the grade of endoscopic esophagitis. Half of these patients can be kept on minimal therapy after a period of 3–4.5 years with maintenance of improvement, while the remainder still need proton pump inhibitors for control.