中药消痈溃得康对乙酸胃溃疡模型大鼠TFF-2表达的影响

目的研究消痈溃得康对乙酸法大鼠胃溃疡模型治疗作用的分子机制。方法将大鼠随机分为正常对照组、假手术对照组、胃溃疡模型组、消痈溃得康治疗组及奥美拉唑治疗组。局部注射乙酸法制备胃溃疡模型,术后第2天开始给药,术后第12天取材,取血清,ELISA方法检测血清三叶因子-2(trefoilfactorfamily2,TFF-2)含量。取溃疡局部胃组织,一部分胃组织用Trizol方法提取RNA,RT-PCR法检测胃组织TFF-2mRNA表达,另一部分胃组织匀浆,ELISA方法检测胃组织TFF-2蛋白表达量。结果模型组大鼠胃组织TFF-2mRNA表达水平明显高于正常对照组和假手术对照组(P0.05),模型组大鼠胃组织及血清TFF-2蛋白含量高于正常对照组和假手术对照组,但统计学差异不显著。消痈溃得康治疗组和奥美拉唑治疗组大鼠胃组织TFF-2mRNA和蛋白表达水平及血清TFF-2蛋白含量明显高于胃溃疡模型组(P0.05)。结论消痈溃得康促进胃溃疡愈合作用的分子机制之一可能是与其上调胃组织TFF-2mRNA及蛋白表达有关。     

A comparison of community pharmacists' views of over-the-counter omeprazole and simvastatin

PURPOSE: Simvastatin and omeprazole were re-classified to pharmacy status in Great Britain in summer 2004. The purpose of this study was to compare the views of community pharmacists on over-the-counter (OTC) omeprazole and simvastatin. METHODS: A pre-piloted questionnaire mailed to 2000 randomly selected community pharmacy premises, with open questions relating to pharmacists' views. Pharmacists' attitudes on aspects of supply were sought using Likert scales. Content analysis was performed on responses to the open question and Wilcoxon signed ranks test (z) used to compare responses to the attitudinal statements. RESULTS: One thousand one hundred and fifty-six questionnaires were returned (57.8%). Themes around omeprazole illustrated positive views compared to concerns relating to simvastatin. Whereas omeprazole was seen as a welcome addition, there were issues around the poor evidence base for simvastatin. Further simvastatin related concerns were in areas of cardiovascular risk assessment, adverse drug reactions and likelihood of patients not committing to therapy. For both agents, excessive cost was an issue. Nearly three-quarters of pharmacists agreed they were entirely confident about selling omeprazole (835, 73%), significantly more than simvastatin (691, 60%); (z = 9.243, p < 0.001). CONCLUSIONS: Two re-classified medicines have raised common and product-specific themes. Many themes relate to clinical governance such as evidence-based practice, risk management and continuing professional development (CPD). Views on the availability and circumstances surrounding the OTC supply differ in certain regards, for example, more believe that they should be involved in the sale of simvastatin personally than for sales of omeprazole.     

单剂量口服奥美拉唑在中国回族和汉族健康人体的药代动力学

目的研究奥美拉唑肠溶片(抗溃疡药)在回族和汉族健康受试者的药代动力学。方法健康回族和汉族受试者各10名,男、女各半,单剂量口服奥美拉唑肠溶片40mg后,用反相高效液相色谱法测定人血浆中奥美拉唑的浓度。用DAS2.0药代动力学软件进行数据处理,SPSS11.5软件进行统计分析。结果回族和汉族受试者的主要药代动力学参数:Cmax分别为(941.94±446.08)和(760.49±581.23)μg.L-1;tmax分别为(2.7±0.68)和(2.70±0.82)h;t1/2分别为(2.43±2.83)和(1.60±1.28)h;AUC0-12分别为(2.29±1.12)和(1.44±7.98)mg.h.L-1;AUC0-∞分别为(2.33±1.11)和(1.47±7.69)mg.h.L-1。结论回族、汉族受试者的Cmax,AUC0-12,AUC0-∞个体间差异较大;但2民族主要药代动力学参数差异无统计学意义。     

CYP2C19基因多态性对奥美拉唑药动学与相对生物利用度的影响

目的在中国男性健康受试者中研究CYP2C19基因多态性对奥美拉唑药代动力学及不同奥美拉唑制剂相对生物利用度的影响。方法筛选18名男性健康志愿者,其中CYP2C19野生型(w/w)、CYP2C19突变杂合子(w/m)、CYP2C19突变纯合子(m/m)各6名。采取随机双交叉试验,受试者随机口服试验制剂或参比制剂奥美拉唑肠溶胶囊40mg。抽取血样3ml至给药后12h。1wk后交叉服药。采用LC/MS法测定血浆奥美拉唑浓度,用3P97软件进行个体药动学建模并估算药动学参数。结果w/w、w/m、m/m组参比制剂奥美拉唑的AUC与Cmax分别为1178.44±340.24、2328.10±1011.83、5062.02±1097.29μg.h.L-1与602.87±118.25,926.43±134.48,1406.29±233.58μg.L-1,3组间差异存在显著性(P<0.05)。ke、CL/F、T21和Vd/F也均存在组间差异(P<0.05)。w/w、w/m、m/m组试验制剂奥美拉唑的AUC与C/max分别为1224.82±531.67、2723.34±519.29、5692.49±1575.35μg.h.L-1与618.74±231.43、910.67±125.99、1303.31±152.01μg·L-1,3组间差异存在显著性(P<0.05)。3组间的ke、CL/F、T21和Vd/F等参数差异均有显著性(P<0.05)。w/w、w/m、m/m组奥美拉唑的相对生物利用度分别为94.29%±14.06%、93.08%±11.22%、91.84%±13.03%,3组间差异无统计学意义(P>0.05)。结论不同的CYP2C19基因型,表现为不同的CYP2C19酶活性,影响奥美拉唑的血药浓度和体内药动学过程。临床患者在使用奥美拉唑治疗前进行CYP2C19基因分型,将有利于优化个体治疗方案。CYP2C19基因多态性对奥美拉唑的相对生物利用度无影响。     

雷贝拉唑与奥美拉唑治疗反流性食管炎临床比较研究

目的比较雷贝拉唑与奥美拉唑治疗反流性食管炎（RE）的疗效。方法随机将符合RE诊断标准的86例患者分为雷贝拉唑治疗组43例和奥美拉唑对照组43例。治疗8周后分别作出症状评价及胃镜评价。结果治疗8周后,治疗组症状改善优于对照组,有显著性差异（P〈0.05）;胃镜下疗效观察结果显示治疗组显著优于对照组（P〈0.05）。结论雷贝拉唑治疗RE的疗效明显优于奥美拉唑。     

Omeprazole 10 Milligrams Once Daily,Omeprazole 20 Milligrams Once Daily,or Ranitidine 150 Milligrams Twice Daily,Evaluated as Initial Therapy for the Relief of Symptoms of Gastro-oesophageal Reflux Disease in General Practice

Background: The efficacy of omeprazole, 20 mg once daily, in the treatment of reflux oesophagitis and the therapeutic advantages over the histamine H₂ receptor antagonists are well documented. This study assessed 20 mg omeprazole daily (OM20), 10 mg omeprazole daily (OM10), and 150 mg ranitidine (RAN) twice daily for symptom relief in gastro-oesophageal reflux disease (GORD). Methods: Patients (n = 994) presenting with heartburn to their general practitioner underwent endoscopy to exclude peptic ulcer disease and were randomized into a UK, multicentre, parallel-group, double-blind comparison of the three treatments for 4 weeks. Symptoms were assessed at clinic visits after 2 and 4 weeks. Results: Symptom relief after 4 weeks was achieved by 61 % (OM20), 49% (OM10), and 40% (RAN) patients (OM20 versus OM10, P < 0.0167; OM20 versus RAN, P < 0.0001; OM10 versus RAN, P < 0.01). Among the patients (32%) with erosive reflux oesophagitis, symptom relief was achieved in 79% (OM20), 48% (OM10), and 33% (RAN) (OM20 versus OM10, P < 0.0001; OM20 versus RAN, P < 0.0001; OM10 versus RAN, NS). Conclusion: Omeprazole, 20 mg, is the most effective initial therapy for relief of GORD symptoms.     

Early or Late Operation in the Treatment of Crohn's Disease

The present report describes the long-term effects of antrectomy, antrum exclusion, portacaval shunt, omeprazole treatment, or the combination of omeprazole treatment and portacaval shunt on the number and density of somatostatin cells in the oxyntic mucosa of the rat. Antrectomy, which is associated with hypogastrinemia, raised the number and density of the somatostatin cells, whereas antrum exclusion and omeprazole treatment, which are associated with hypergastrinemia, reduced the number and density of the somatostatin cells. Portacaval shunt, which is associated with hypogastrinemia, increased both the number and the density. Omeprazole treatment of portacava-shunted rats suppressed or even reversed the somatostatin cell hyperplasia after portacaval shunt alone. From these findings it is unlikely that gastrin stimulates the proliferation of somatostatin cells in the oxyntic mucosa. In fact, there seems to be an inverse relationship between the serum gastrin concentration and the somatostatin cell number.     

CYP2C19多态性对奥美拉唑药代动力学的影响

目的:研究中国健康受试者细胞色素P4502C19(CYP2C19)多态性对奥美拉唑体内药代动力学的影响。方法:筛选12名健康男性和12名健康女性受试者,采用随机分组、双交叉的试验方案,每组分别服用一种奥美拉唑7d,洗脱期7d,第2周期交换用药。用LC-MS/MS方法测定每周期第1天和第7天多个时间点血药浓度,计算两种奥美拉唑的药代动力学参数。检测受试者基因位点CYP2C19*2(681G>A)和CYP2C19*3(636G>A),按照基因型分成快代谢型、中等代谢型和慢代谢型。结果:慢代谢型、中等代谢型和快代谢型在药代动力学参数t1/2、MRT0-t、CL、Vd、AUC0-t、AUC0-∞中存在显著性差异(P<0.05),连续给药后基因多态性对药物代谢的影响相对减小。结论:CYP2C19多态性与奥美拉唑的代谢密切相关,临床上应关注基因多态性对奥美拉唑代谢的影响。     

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.     

In vitro functional analysis of 24 novel CYP2C19 variants recently found in the Chinese Han population

Abstract

1. CYP2C19 is a highly polymorphic enzyme responsible for the metabolism of a wide range of clinical drugs. Alterations to the CYP2C19 gene contribute to the variability of CYP2C19 enzyme activity, which causes pharmacokinetics and drug efficacies to vary and adverse drug reactions to occur in different persons. Recently, we identified 24 novel CYP2C19 allelic variants in the Chinese Han population. The purpose of present study is to assess the impact of these newly found nucleotide mutations on the enzymatic activity of the CYP2C19 protein.

2. Dual-expression vectors were constructed and transiently transfected into 293FT cells. Forty-eight hours after transfection, cells were re-suspended and incubated with two typical probe substrates, omeprazole and S-mephenytoin, to determine the activities of each variant relative to the wild-type protein.

3. Immunoblotting results showed that the protein expression levels of the CYP2C19 variants were diverse. Enzymatic ability analysis showed that the variant 35FS exhibited no functional activity, and most of the other variants showed significantly decreased metabolic activities toward both omeprazole and S-mephenytoin compared with wild-type.

4. These findings greatly enrich the knowledge of biological effects of these newly found CYP2C19 mutations and aid the application of this knowledge to future individualized drug therapy in clinic.