新型在线柱萃取高效液相色谱法测定异烟肼的血药浓度

目的建立新型在线柱萃取HPLC法测定人血浆中异烟肼血药浓度,用于异烟肼的日常治疗药物监测。方法新型在线柱萃取HPLC由萃取系统和分析系统两部分构成。萃取柱为Aston RG SCX（20 mm×4.6 mm,5μm,ANAX）,分析柱为Aston RG C18（250 mm×4.6 mm,5μm）;两系统通过六通阀连接,采用＂中心切割＂模式及陷阱柱转移目标物;检测波长为340 nm,样品经蛋白沉淀、衍生,进样量为50μL,采用外标法计算结果。结果异烟肼在0.18～35.84μg.mL^-1与峰面积呈良好线性关系,相关系数为0.999 8,最低检测限为0.02μg.mL^-1,低（0.18μg.mL^-1）、中（2.24μg.mL^-1）、高（35.84μg.mL^-1）浓度的绝对回收率为91.6%～95.9%,日内和日间RSD均〈5.0%,准确度为98.7%～101.5%。结论本方法具有抗干扰能力强、自动化程度高、准确度和精密度好等优点,完全适合异烟肼的日常治疗药物监测。     

左乙拉西坦单药治疗不同类型婴幼儿癫痫的临床效果和安全性

目的 探析不同类型婴幼儿癫痫应用左乙拉西坦单药治疗的临床效果和安全性.方法 选取本院2011年1月～2012年12月收治的50例不同类型婴幼儿癫痫患儿作为观察对象,入院后应用左乙拉西坦单药治疗,2次/d,服用起始总剂量为10mg/（kg·d）,根据患者的实际病情每5日增加5～10 mg/（kg·d）,维持治疗剂量为20～40mg/（kg·d）,约2周平均剂量增加到35mg/（kg·d）,观察50例患者的临床症状改变情况和不良反应发生情况.结果 50例患者均完成了药物治疗,其中显效26例,有效14例,无效10例,总有效率为80.0％,患者有情绪焦躁、行为异常和嗜睡的不良反应.结论 不同类型婴幼儿癫痫患儿应用左乙拉西坦治疗有明显的治疗效果,特别是部分型和肌阵挛发作患儿治疗效果良好,药物治疗过程中不良反应发生少,是一种安全有效的抗癫痫药物,可以在临床推广.     

硫酸氨基葡萄糖氯化钾的制备及对大鼠骨关节炎模型的治疗作用

目的：制备硫酸氨基葡萄糖氯化钾,考察其对大鼠骨关节炎模型的治疗作用。方法：以甲壳素为原料,经盐酸水解得盐酸氨基葡萄糖,将其与硫酸钾置于水溶液中,通过充分的离子交换反应,并加入作为沉淀剂的有机溶剂,制备硫酸氨基葡萄糖氯化钾;考察反应温度、反应溶液中各离子平衡时间、反应原料配比以及沉淀剂的种类、加入量和加入时间等对最终产物的影响,优化制备工艺。建立木瓜蛋白酶诱导的大鼠骨关节炎模型,并灌胃给予硫酸氨基葡萄糖氯化钾,通过血清中丙二醛和一氧化氮含量测定、关节肿胀度观察和关节软骨病理切片检查,考察硫酸氨基葡萄糖氯化钾对模型大鼠骨关节损伤的保护作用。结果：确立优化的硫酸氨基葡萄糖氯化钾制备工艺：反应温度为45~55℃,离子平衡时间为0.5 h,盐酸氨基葡萄糖与硫酸钾的质量配比为22.5：7.15,作为沉淀剂的乙醇加入浓度约为75%及加入时间为3 h。骨关节炎模型大鼠接受硫酸氨基葡萄糖氯化钾给药后,血清中丙二醛和一氧化氮含量显著降低（P〈0.05或P〈0.01）,关节肿胀度明显减轻（P〈0.01）,且病理切片显示,仅有少许关节软骨细胞轻度变性,软骨未见明显坏死,细胞未见明显增生。结论：优化的硫酸氨基葡萄糖氯化钾制备工艺适用于工业化生产;硫酸氨基葡萄糖氯化钾对骨关节炎损伤具有显著保护作用,且效果好于盐酸氨基葡萄糖。     

Transdermal delivery of calcium channel blockers for hypertension

Introduction: Calcium channel blockers are a very important class of antihypertensive drugs. Most calcium channel blockers (CCBs) exhibiting low oral bioavailability are required to be taken more than once a day due to their short half-lives which result in poor patient compliance. There is an ineluctable requirement for improved drug-delivery devices for CCBs because of the quantum of their utilization and shortcoming associated with their conventional dosage forms.

Areas covered: There have been worthwhile research endeavors worldwide to investigate the skin permeation and to develop transdermal formulations of various categories of CCBs. This review explores the investigations on the feasibility and applicability of systemic delivery of various CCBs via skin.

Expert opinion: Transdermal delivery of CCBs has been particularly acknowledged as a potential drug-delivery route in the therapy of hypertension. Several overtures have been made to enhance delivery of these drugs via skin barrier. There have been remarkable research endeavors worldwide to investigate the skin permeation and to develop transdermal systems of various CCBs. Persistent advancement in this area holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later.     

Intranasal insulin therapy for cognitive impairment and neurodegeneration: current state of the art

Introduction: Growing evidence supports the concept that insulin resistance plays an important role in the pathogenesis of cognitive impairment and neurodegeneration, including in Alzheimer's disease (AD). The metabolic hypothesis has led to the development and utilization of insulin- and insulin agonist-based treatments. Therapeutic challenges faced include the ability to provide effective treatments that do not require repeated injections and also the ability to minimize the potentially hazardous off-target effects.

Areas covered: This review covers the role of intranasal insulin therapy for cognitive impairment and neurodegeneration, particularly AD. The literature reviewed focuses on data published within the past 5 years as this field is evolving rapidly. The review provides evidence that brain insulin resistance is an important and early abnormality in AD, and that increasing brain supply and utilization of insulin improves cognition and memory. Emphasis was placed on discussing outcomes of clinical trials and interpreting discordant results to clarify the benefits and limitations of intranasal insulin therapy.

Expert opinion: Intranasal insulin therapy can efficiently and directly target the brain to support energy metabolism, myelin maintenance, cell survival and neuronal plasticity, which begin to fail in the early stages of neurodegeneration. Efforts must continue toward increasing the safety, efficacy and specificity of intranasal insulin therapy.     

Factors to consider when selecting a nebulizer for a new inhaled drug product development program

Introduction: Nebulizers are a common device choice for use when developing a new drug product, but the range of nebulizer devices available can make it difficult to select the right device. Increasingly, companies are only able to promote a drug with the device that was used during the development program; therefore, choosing the best device at an early stage is important in order to achieve commercial success. Selecting a device that is inappropriate for the intended drug can result in poor drug delivery from the nebulizer to the patient, which would have obvious implications for the development program. As device performance varies, it is important to ensure that the most appropriate device is chosen for the intended drug to ensure optimal drug delivery to the patient population.

Areas covered: In this review, the types of nebulizer devices available are highlighted, and the factors that should be taken into consideration when selecting the most appropriate device for a new drug are discussed. The review is broadly divided into drug, device, patient and trial characteristics.

Expert opinion: Efficient nebulizer devices that combine electronic monitoring capabilities as a form of telehealth are likely to provide superior drug delivery to patients and accurate clinical trial data. Their use in adaptive clinical trials may help to vastly reduce the time and costs associated with achieving drug approval.     

恩替卡韦治疗尿毒症合并失代偿期乙型肝炎肝硬化的疗效观察

目的:观察延长恩替卡韦用药间隔时间治疗乙肝病毒定量(HBV-DNA)阳性的尿毒症合并失代偿期肝硬化患者的药物疗效。方法:选择HBV-DNA≥10~4拷贝·m L~(-1)的尿毒症合并失代偿期肝硬化患者65例,给予恩替卡韦0.5 mg/次,每5 d 1次,透析后口服。观察患者治疗前及治疗3月、6月、12月、24月的丙氨酸氨基转移酶(ALT)、血清总胆红素(TBIL)、血清白蛋白(ALB)、凝血酶原活动度(PTA)、HBV-DNA定量、Child-Pugh评分、肝脏B超等,记录并发症发生情况。结果:ALT、TBIL、ALB、Child-Pugh评分均在治疗第3月后较治疗前改善,差异有显著性(F值分别是3.83,3.19,19.39,3.24,P值分别是0.008,0.019,0.001,0.01)。ALT、TBIL治疗3月后组间数值无显著差异(P>0.05)。ALB、Child-Pugh评分在治疗后第3月、6月、12月组间数值明显改善,差异有显著性(P<0.05),但第12月与第24月之间无差异(P>0.05)。PTA是在第6月明显升高,与治疗前差异有显著性(F=25.10,P=0.001),但第6月后数值比较无显著差异(P>0.05)。HBVDNA在第24月阴转率100%。结论:HBV-DNA阳性的尿毒症合并失代偿期肝硬化患者间隔5 d服用恩替卡韦0.5 mg治疗能快速抑制病毒复制,有效改善肝功能,减少并发症的发生,阻止或延缓病情进展,预防肝癌发生。     

Propensity to Work Among Chronically Unemployed Adult Drug Users

Analyses were conducted to compare rates of employment before, during, and after employment at the therapeutic workplace, which is a novel employment-based treatment for drug misuse. Participants in two clinical trials attended the therapeutic workplace at higher rates than they worked before intake and six months after discharge. These data suggest that unemployed chronic drug misusers will attend work at higher rates at the therapeutic workplace than in the community when paid modest wages, and that the failure of chronic drug misusers to obtain employment in the community may not result from lack of interest in work.     

Chapter 10. Perspectives on Treatment,Alliance and Narratives Concerning Substance Use-Related Dependency

This article considers different perspectives on the treatment of substance use-related dependency, focusing on the importance of a therapeutic relationship, working alliance, counseling, and the use of narrative methods. The article also discusses some unresolved critical issues concerning the possibilities and limitations of acquiring necessary knowledge about substance use-related dependency when using narrative research methods. The main conclusion is that the therapeutic relationship between the therapist and the client is of crucial importance for a positive outcome of treatment and that narrative methods provide a detailed empirical database for analyses of substance use-related dependency.     

Fixed combinations of dorzolamide-timolol and brimonidine-timolol in the management of glaucoma

Importance of the field: The emergence of fixed-combination drugs for the treatment of glaucoma has, to some extent, changed the medical management of glaucoma. The potential benefits of these drugs include a reduction in the total number of drops and preservatives instilled per day and improved patient comfort factors, which may contribute to better compliance. Combination medications may also improve therapeutic efficacy and play an important role in controlling medication cost. However, the fixed dosing may be a disadvantage in some cases.

Area covered in this review: This review describes the composition, pharmacokinetics, mode of action, efficacy, side effects, and safety profile of fixed-combination dorzolamide–timolol and fixed-combination brimonidine–timolol.

What the reader will gain: Understanding of the pros, cons, and safety profile of two FDA approved fixed-combination antiglaucoma medication.

Take home message: Fixed-combination medications may be a reasonable adjunct to prostaglandins if a large drop in the intraocular pressure (IOP) is desired and adding only one medication is unlikely to reach the target IOP range. Both mentioned drugs are effective in reducing the IOP and further clinical studies will help identify differences in efficacy between the two. The clinician must make an individualized assessment of the medication's risk-benefit profile for each patient.