埃索美拉唑相关药物性肝损害

1名54岁女性患者，因十二指肠球部溃疡口服埃索美拉唑20mg，1次／d、吉法酯50mg，3次／d、铝碳酸镁500mg，3次／d。服药近半月后逐渐出现食欲减退、尿色加深，继续服用1月余后出现巩膜黄染、伴皮肤瘙痒。门诊检查肝功能示：AST890 U／L，ALT 1123 U／L，ALP 204 U／L，,γ-GT 277 U／L，TBil 169．7μmol／L，DBil 99．7iμmol／L，IBil 70．0 μmol／L，TBA 234．6μmol／L。入院后停用埃索关拉唑，给予还原型谷胱甘肽和硫普罗宁治疗，1周后患者巩膜黄染逐渐消退，尿色恢复正常，3周后复查肝功能，明显好转出院。     

Ventricular bigeminy associated with voriconazole, methadone and esomeprazole

CASE: We report a case of ventricular bigeminy with concomitant administration of methadone, voriconazole and esomeprazole in a Caucasian woman aged 26 with acute lymphoblastic leukaemia. Plasma concentrations of voriconazole and methadone were high, 12.4 mg/l (therapeutic range: 1-4 mg/l) and 1.6 mg/l (therapeutic range: 0.2-0.4 mg/l), respectively. In the absence of esomeprazole, no more episode of cardiac arrhythmia occurred and 7 days after, methadone plasma concentration fell at 0.57 ml/l while voriconazole concentration was at 5.5 mg/l. We speculate that a pharmacokinetic interaction between methadone and voriconazole was amplified by the addition of esomeprazole. This led to the large increase of the plasma concentration of methadone and was potentially responsible for its cardiac toxicity. CONCLUSION: Physicians should be aware of the potential interaction between voriconazole, esomeprazole and methadone leading to arrhythmia. The inhibitory potential of voriconazole is possibly increased by esomeprazole.     

住院精神病人伴发低钾血症105例心电图分析

目的：探讨低钾血症心电图变化特征及与血清钾浓度的关系。方法：将105例患者的心电图特征及血清钾浓度作对比分析。结果：低钾血症的心电图表现为U波明显、T-U融合、Q—T或Q—u间期延长、ST段下移、T波改变和心律失常;心电图与血清钾浓度有较好的一致性,心电图异常表现的发生率与低钾症的严重程度有关。结论：临床上低钾血症心电图的各种异常表现,有助于及时发现低钾血症和指导治疗。     

Cost reduction associated with restriction policy on dispensing intravenous esomeprazole in lebanon

Objectives To assess the impact of the pharmacist on cost through simple implementation of restriction policy on IV drug usage during pharmacy dispensing procedure. Setting In-patient floors of a Hospital. Methods All medication orders for IV esomeprazole, received at the pharmacy during a 24-month period, were reviewed for appropriate IV route of administration. Two separate time intervals, pre- and post- implementation of restriction dispensing policy, were used to determine cost impact of pharmacy intervention. Main Outcome Measure The cost difference between pre- and post-restriction periods. Results During the pre-restriction period, the majority of esomeprazole IV vials were dispensed to patients able to tolerate oral medications and who were admitted to non-intensive care units. The average monthly consumption of IV esomeprazole was 1,439 vials in the pre-restriction period as compared to 346 vials in the post-restriction period. Therefore, the associated cost was reduced by an average of $21,233 per month. Conclusion Even though the clinical role of pharmacy practice in Middle Eastern countries is limited, this study highlighted the impact of the pharmacist on cost through the implementation of restriction policy during dispensing procedure, leading to a cost reduction by four folds.     

Acetylsalicylic acid/esomeprazole fixed-dose combination

The fixed-dose acetylsalicylic acid (ASA)/esomeprazole capsule combines the cardiovascular (CV) protective effects of low-dose ASA with the gastroprotective effects of the proton pump inhibitor esomeprazole. It is approved for use as a convenient once-daily regimen in the prevention of CV and cerebrovascular events in patients requiring continuous low-dose ASA who are at risk of developing gastric and/or duodenal (peptic) ulcers. In two large, 26-week, randomized, double-blind, multinational, phase III trials (ASTERIX and OBERON) in patients who were receiving low-dose ASA for the prevention of CV events and who had an increased risk of ulcer development, the incidence of endoscopy-proven peptic ulcers (primary endpoint) was significantly lower with the addition of esomeprazole 20?mg/day versus placebo. Moreover, patient-reported dyspeptic symptoms (epigastric pain and epigastric burning) were reported in significantly fewer patients in the low-dose ASA plus esomeprazole group than in the low-dose ASA plus placebo group. Low-dose ASA plus esomeprazole treatment was generally well tolerated, with a similar adverse event profile to that seen with low-dose ASA plus placebo.     

CAPD患者入院时低钾血症的发生率及其临床意义

目的　了解门诊腹膜透析 (CAPD)患者入院时低钾血症的发生率及其与临床特点的关系。方法　采用电极法测定 1997～ 2 0 0 3年 1月间我院 4 1例门诊 CAPD患者入院时的血钾浓度 ,并结合临床及实验室资料进行分析。结果　CAPD患者入院时的血钾浓度为 3.6 5± 0 .82 mmol/ L,其中 2 3例患者血钾正常 (3.5～ 5 .5 mm ol/ L) ,17例患者为低钾血症 (<3.5 m mol/ L ) ,1例患者血钾增高 (>5 .5 mmol/ L )。 CAPD患者的血钾浓度与血清白蛋白(r=0 .5 2 ,P<0 .0 5 )、尿素氮 (r=0 .6 8,P<0 .0 1)和肌酐 (r=0 .5 0 ,P<0 .0 5 )呈正相关。低钾血症组患者的血钾浓度明显低于非低钾血症组 (2 .94± 0 .4 3m mol/ L vs4 .15± 0 .6 4 mm ol/ L,P<0 .0 1) ;CAPD患者低钾血症的发生与入院前蛋白质摄入不足 (P<0 .0 1)、尿量较多 (P<0 .0 1)、高腹透出超量 (P<0 .0 5 )关系密切。结论　门诊 CAPD患者入院时低钾血症的发生率较高 ;低钾血症的发生与入院前患者蛋白质摄入不足、钾离子丢失过多关系密切 ;低钾血症可以作为 CAPD患者营养不良的指标之一 ;及时发现与纠正低钾血症有助于提高 CAPD患者的生活质量与长期存活率。     

Clinical efficacy of esomeprazole in the prevention and healing of gastrointestinal toxicity associated with NSAIDs in elderly patients

NSAIDs are widely prescribed for the treatment of pain, inflammation and rheumatic disorders, but their use is associated with adverse gastrointestinal effects, ranging from dyspeptic symptoms and peptic ulcers to more serious complications. Elderly patients are at high risk of experiencing NSAID-induced gastrointestinal tract injury and should be considered candidates for prophylactic pharmacological therapy. In studies conducted in adult patients, proton pump inhibitors (PPIs) such as esomeprazole have been shown to prevent or reduce NSAID-induced gastrointestinal injury. The beneficial effects of esomeprazole can be ascribed largely to its ability to maintain sustained inhibition of gastric acid secretion, although there is evidence to suggest that pharmacodynamic properties unrelated to acid inhibition may also contribute to the gastroprotective effects of this agent. Although there are limited data on the use of esomeprazole specifically in elderly patient populations, studies of patients at high risk of NSAID-induced gastrointestinal toxicity because of advanced age indicate that this PPI is both effective and well tolerated when administered in conjunction with NSAIDs. Thus, esomeprazole can be regarded as a useful option for prophylactic therapy in elderly patients receiving long-term NSAID therapy.     

埃索美拉唑治疗幽门螺旋杆菌相关性消化性溃疡

目的:观察埃索美拉唑治疗消化性溃疡的临床疗效及对幽门螺杆菌(HP)感染的清除率。方法:98例消化性溃疡患者,其中埃索美拉唑组48例,给埃索美拉唑20mg,Po,bid,共1周,安慰剂3周;奥美拉唑组50例,给奥美拉唑20mg,Po,bid,共3周。疗程结束时,复查胃镜观察溃疡的愈合情况。结果:埃索美拉唑组胃溃疡腹痛消失时间为(2.8±1.2)d,十二指肠溃疡为(1.8±0.5)d;奥美拉唑组分别为(3.8±1.9)d和(2.6±1.0)d,经统计学处理有显著性差异(P<0.01)。溃疡的愈合率和HP清除率,与奥美拉唑组70%和60%相比(P<0.01),埃索美拉唑组分别为95.8%和91.7%。结论:埃索美拉唑能明显缓解消化性溃疡症状,止痛效果快,对溃疡有较高的愈合率及HP清除率。     

埃索美拉唑在治疗幽门螺杆菌感染的消化性溃疡中的地位

目的 比较埃索美拉唑三联与奥美拉唑三联疗法治疗幽门螺杆菌(Hp)阳性消化性溃疡临床疗效.方法 将60例经内镜诊断并检测证实Hp阳性的消化性溃疡患者随机分为两组.埃索美拉唑组(30例):埃索美托唑20 mg+阿莫西林1 g+克拉霉素500 mg,每日2次,共7 d;奥美拉唑组(30例):奥美拉唑20 mg+阿莫西林1 g+克拉霉素500 mg,每日2次,共7 d.疗程结束4周后复查胃镜并检测Hp,观察腹痛缓解率、溃疡愈合率、Hp根除率及用药后的不良反应等.结果 埃索美托唑组和奥美拉唑组溃疡愈合率分别为90.1%和83.9%,Hp根除率分别为94.2%和83.7%,差异有统计学意义(P＞0.05).两组用药后不良反应少,有较好的安全性.结论 埃索美托唑三联疗法治疗Hp阳性的消化性溃疡安全有效,优于奥美拉唑三联疗法.     

LC-MS/MS法分析埃索美拉唑钠杂质

目的对埃索美拉唑钠的主要杂质进行结构分析。方法采用资生堂MGII(4.6 mm×250 mm,5μm)色谱柱,以20 mmol·L~(-1)乙酸铵溶液(A)-乙腈(B)=75∶25为流动相,进行等度洗脱,流速1 m L·min~(-1),柱后1∶1分流,采集杂质谱的质谱数据,结合质谱的裂解规律,并对该结构进行初步验证。结果在所建立的条件下,杂质谱中埃索美拉唑钠及其杂质分离良好,共检测到4个较大杂质峰,并分析了杂质B、杂质C、杂质D的结构。结论建立的LC-MS/MS法能有效地洗脱、分离埃索美拉唑钠的杂质,并分析其杂质,为埃索美拉唑钠的质量控制和工艺优化提供了参考依据。     

Overcoming immunogenicity associated with the use of biopharmaceuticals

The safety and efficacy of biopharmaceuticals can be severely impaired by their immunogenicity. A risk-based strategy should be used to assess immunogenicity on a case-by-case basis using standardized methods to correlate anti-drug antibody levels with clinical outcome. In silico and in vitro techniques allow putative T-cell epitopes to be identified and eliminated in candidate molecules while maintaining structure and function. Putative T-cell epitopes can be studied in the context of the HLA allotypes representative of the target population in vitro and in transgenic mice that express human HLA genes. Mice immune tolerant to human proteins allow the study of the effect of factors such as aggregation on the loss of immune tolerance. However, significant challenges remain in order to be able predict the immunogenicity of a therapeutic protein in a particular individual.     

Risks associated with the therapeutic use of fluoroquinolones

Introduction: Quinolones are among the most often prescribed antimicrobial agents. Some types of toxicity observed during therapy with these drugs have gained much attention.

Areas covered: Here, we review the potential of the most widely used fluoroquinolones, ciprofloxacin, levofloxacin and moxifloxacin for adverse reactions. The rates of adverse events are similar for quinolones and other antibacterial agents. However, quinolone therapy can be associated with specific risks, which must be weighed against their benefit. In some studies, use of quinolones was associated with Clostridium difficile-associated diarrhea. Patients with impairments of the CNS (e.g., epilepsy or arteriosclerosis) should not be treated with quinolones. They should be avoided in patients with known prolongation of the QT interval or other risk factors for tachyarrhythmia. The risk for quinolone-associated tendinopathy is more pronounced among elderly persons, non-obese patients and individuals with concurrent use of glucocorticoids or chronic renal diseases. Quinolones are contraindicated in children because they cause destruction of the immature joint cartilage in animals. The use in paediatrics is restricted to life-threatening infections.

Expert opinion: Changes in the resistance situation and newly recognized adverse reactions require a continuing adjustment of therapeutic recommendations and constant educational efforts in the field of antimicrobial therapy.     

Hypersensitivity pneumonitis associated with the use of trofosfamide

Trofosfamide (Ixoten; Baxter Oncology, Germany) is an alkylating agent that, as with other oxazaphosphorine derivatives, has to be activated by hepatic cytochrome P450 oxidases. The bioavailability is nearly 100% after oral application, and the main metabolites are 4-hydroxytrofosfamide, and 4-hydroxyifosfamide. The main side-chain metabolites ifosfamide and cyclophosphamide can be further activated by oxidation and formation of their respective phosphoramide mustards. Oral continuous low-dose therapy has been the most widely used schedule. The toxicity profile consists mainly of dose-dependent hematotoxicity and, rarely, hemorrhagic cystitis. Nausea and vomiting are infrequently seen. Higher grades of nephrotoxicity or neurotoxicity--side-effects that typically limit the use of ifosfamide-have not been reported with low-dose continuous trofosfamide treatment. We report herein a case of a 83-year-old female patient with a disseminated malignant peripheral nerve sheath tumor treated with trofosfamide developing pulmonal toxicity. To our knowledge, this is the first reported case of exogenous allergic alveolitis after exposure to this drug.     

埃索美拉唑的药动学

埃索美拉唑(esomeprazole)是奥美拉唑的S-异构体,是第一个以单一异构体存在的质子泵抑制剂(PPI),与奥美拉唑相比,其代谢过程具有立体选择性,从而较奥美拉唑拥有更高的生物利用度和更为一致的药动学,抑酸作用优于奥美拉唑和其他PPI.     

A cotwin-control analysis of drug use and abuse/dependence risk associated with early-onset cannabis use

We assessed whether, after controlling for genetic and shared environmental influences, early cannabis use remains a significant predictor of other drug use, abuse, and dependence, and whether the risk for early-users is greater than that for later cannabis users. Data from a 1992 telephone diagnostic interview of 8169 male twins (M = 42.0 years at interview) who served in the U.S. military during the Vietnam-era were used to identify a subsample of 293 monozygotic (MZ) and dizygotic (DZ) twin pairs discordant for early cannabis use (before age 18). Using cotwin-control analyses, outcomes assessed were: lifetime illegal drug use (stimulant/cocaine, sedative, opiate, and hallucinogen/PCP), lifetime DSM-III-R illegal drug abuse/dependence, and lifetime DSM-III-R alcohol dependence. After controlling for covariates, early cannabis users were at greater risk than their later/never-using cotwins for 8 of 9 substance-related comparisons, including: using other illegal drugs (ORs: 2.71–4.09), having illegal drug abuse/dependence (ORs: 2.02–2.13), and developing alcohol dependence (OR = 2.36). When analyses were limited to pairs in which the cotwin used cannabis later, early and later-users only differed significantly on sedative, opiate, and hallucinogen use. After familial influences on early cannabis use were controlled for, cannabis use—regardless of the age of initiation—still conferred increased risk of other illegal drug use, drug abuse/dependence, and alcohol dependence. In contrast to previous research, there is limited evidence for increased risk associated with early-onset use in this sample of Vietnam-era veterans.     

埃索美拉唑对大鼠应激性溃疡的保护作用

目的:研究埃索美拉唑对大鼠应激性溃疡的保护作用。方法:选择健康的SD雄性大鼠36只,随机分为4组:正常对照组、模型组、埃索美拉唑3 d组和埃索美拉唑7 d组,每组各9只。用药干预组分别灌胃给予埃索美拉唑2．4 mg·kg-13 d和7 d。最后一次给药后各组大鼠禁食24 h,自由饮水。除正常对照组外,其余3组均采用水漫束缚法建立大鼠应激性溃疡模型,分别测定各组大鼠胃内pH值、黏膜的溃疡指数和氨基己糖含量,并在显微镜下观察组织学变化。结果:与模型组比较,埃索美拉唑3 d和7 d组的溃疡指数均明显降低[(32．11±5．88)vs (14．00±5．75),(13．33±6．95),P<0．01];胃黏膜氨基己糖含量均明显增加[(26．51±3．71)vs(35．21±5．75), (38．23±8．09)mg·g-1蛋白,P<0．01],pH值均明显升高[(1．96±0．65)vs(2．74±0．53),(3．31±0．58), P<0．05];7 d组的胃黏膜氨基己糖含量和胃内pH值与正常对照组接近(P>0．05)。组织学切片亦显示,埃索美拉唑3 d和7 d组损伤程度及炎症反应均较模型组减轻,7 d组损伤程度小于3 d组。结论:埃索美拉唑对大鼠应激性溃疡有较好的保护作用,7 d预防效果更显著。其作用机制与增加胃黏膜氨基己糖含量和抑制胃酸分泌有关。