药物基因组学及生物芯片应用

药物基因组学(Pharmacogenomics)主要阐明药物代谢、药物转运和药物靶分子的基因多态性与药物作用,包括疗效和毒副作用之间的关系。药物基因组学将在药学研究中,特别是药物作用机制、药物代谢、提高药物疗效及新药研发等方面发挥重要作用,并将从根本上改变药物临床治疗模式和新药开发方式。笔者通过对药物基因组学的研究内容的分析、阐明,讨论生物芯片与药物基因组学之间的关系,以及药物基因组学的发展前景。     

药物基因组学及生物芯片应用

药物基因组学主要阐明药物代谢、药物转运和药物靶分子的基因多态性与药物作用、包括疗效和毒副作用之间的关系。目前药物基因组学通常是指以快速增长的人类基因组中所有基因信息,指导新药开发的一个领域。药物基因组学有可能从根本上改变药物临床治疗模式和新药开发方式。生物芯片技术在药物基因组学研究中的应用,必将有助于设计针对靶点的更为有效的新型药物,提高临床疾病的诊断和治疗水平。     

药物基因组学与心律失常疾病的治疗

抗心律失常药物的治疗剂量和中毒剂量非常接近,而个体的差异易引起药物的不良反应。为此研究抗心律失常药物的药物基因组学来正确地引导药物的使用,以期达到理想的治疗效果并减少毒副作用。本文就近年来抗心律失常药物基因组学的研究进展作一综述。     

抗肿瘤药物的基因导向性个体化治疗

遗传药理学与药物基因组学的发展对于开展肿瘤的个体化治疗具有非常重要的意义。药物基因组学的发展使得多种影响肿瘤药物的遗传变异得以阐明，并进一步影响肿瘤治疗过程中的新药研发与个体化治疗。本文针对目前明确的能够影响抗肿瘤药物疗效的常见遗传变异进行综述，以促进抗肿瘤药物个体化治疗模式的推广。     

常用抗肿瘤药物基因组学研究进展

药物基因组学的研究进展在指导临床个体化用药、阐明个体差异方面具有重要作用。常用抗肿瘤药物在肿瘤治疗中使用频率最高,是一线方案的首选药物。通过对常用抗肿瘤药物基因组学的分析研究,找到不同患者在基因层面的个体差异,达到预测化疗疗效、选定最佳剂量、减少不良反应的目的,从而实现真正意义上的个体化用药。     

药物基因组学在个体化医疗中的应用进展和实例

目的：介绍药物基因组学目前在国外临床应用的进展和实例．促进其在我国临床实践中的应用．提高个体化医疗的水平。方法：本文根据美国FDA批准的60多个包含药物基因组学信息的药品说明书,结合我们临床用药实际和目前可及的基因检测手段．对药物基因组学在个体化医疗中的实际应用情况进行总结,供临床药师和医师在治疗中尝试、应用或参考。结果与结论：基于基因多态性检测技术的药物基因组学已经广泛应用于临床,在提高药物疗效．降低药物毒副作用,调整药物剂量方面发挥了重要的作用,开辟了个体化医疗的新局面。     

药物基因组学在临床药物治疗中的应用

经验性的药物治疗模式忽略了患者的个体差异,不能最大程度地发挥药物的疗效、规避毒副作用,导致各种不合理用药现象严重。近年来发展的药物基因组学通过关联患者个体的遗传物质与药物的药动学、药效学特性,可以帮助医师、药师预测药物疗效、估算药物剂量、调整给药方案以及预防药物不良反应发生,指导个体化合理用药。本文综述了药物基因组学在临床应用中的最新进展和突出问题,为其临床合理应用与推广提供借鉴。     

抗肿瘤药物靶向制剂的研究进展

抗肿瘤药物毒性较大,为减少全身毒副作用提高靶向部位的药物浓度,人们将抗肿瘤药物制备成各种靶向制剂。本文综述了近年来有关抗肿瘤药物的靶向制剂研究进展。     

大连五院抗肿瘤药物临床应用分析

目的：分析大连五院抗肿瘤药物使用情况,为进一步合理用药提供参考。方法药物利用分析资料来源于大连市第五人民医院计算机药品管理系统。选取2013年接受化疗的肿瘤患者200例,均经手术或病理确诊。以药品销售金额、限定日剂量（DDD）、用药频度（DDDs）、限定日费用（DDC）为评价指标,分析抗肿瘤药物毒副作用的特点及影响因素。结果抗代谢药物,抗肿瘤中成药、植物来源的抗肿瘤药及其衍生物使用频率较高。顺铂、紫杉醇及衍生物、阿霉素类抗肿瘤抗生素的毒副作用发生率较高。结论抗代谢药物、抗肿瘤中成药、植物来源的抗肿瘤药及其衍生物应用较多,抗肿瘤药物毒副作用发生率较高,应进一步加强合理用药水平。     

药物基因组学的研究进展

药物反应的遗传多态性对药物疗效、毒副作用等有决定作用。药物基因组学应用分子遗传新技术研究基因组,加速发展对药物反应的标记（如药物作用目标、药物代谢、疾病通路等）、寻找药物反应的遗传分布,其发展促进了药物遗传学的进步,为疾病治疗和新药设计开辟了广阔的前景。     

高血压药物的不良反应与药物基因组学关系的研究进展

近来,个体差异造成降压药物不良反应的不同越来越受到重视,通过药物基因组学的研究,基因多态性已被认为是造成药物不良反应的首要原因。从基因水平揭示高血压药物不良反应的个体差异是一种有效的方法。本文综述了常用降压药物的不良反应与药物基因组学关系的研究进展,为高血压药物个体化应用于临床治疗应用提供参考依据。     

基因多态性对吉西他滨疗效影响的研究进展

随着药物基因组学、药物遗传学的发展,基因指导下个体化治疗成为提高化疗疗效的有效途径之一。确定药物的相关预测性分子标志物有助于指导临床治疗,提高疗效。吉西他滨（gemcitabine）作为多种肿瘤的有效化疗药物,其疗效与不良反应的差异与相关基因多态性的关系日益受到人们的关注。本文就吉西他滨各相关酶的基因多态性情况及其对疗效的影响进行综述。     

Some applications of pharmacogenomics and epigenetics in drug development and use in pursuit of personalized medicine

Personalized medicine has become the most recent mantra of the pharmaceutical industry. While truly affordable bespoke drugs may never be totally achievable, pharmacogenomics and epigenetics will play significant roles in developing targeted therapy tailored to subpopulations of disease sufferers most likely to benefit. Personalized medicine is a very attractive concept, but an extremely difficult reality to achieve due to theoretical and practical considerations. Foremost among the theoretical reasons is our dearth of knowledge of individual physiology and metabolism, as well as the interactions of genetics and environment in the development of most diseases. Amongst the practical reasons, there is the cost of new drug development, considered to be about 800 million to one billion dollars (J Health Econ 22:151-185, DiMasi et al. 2003; Health Econ 19:130-141, Adams and Vu Brantner 2010) and the fact that many drugs now on the market do display reasonable efficacy in large segments of the population with acceptable side effects. Thus, the market for "personalized" drugs may not be large enough to support the costs of development. Another factor is the limitations put on healthcare by governments and insurance companies which promote the use of generics rather than the creation of new chemical entities. Finally, there are the social and ethical considerations of turning individual biology into noughts and ones with the possibility of such information becoming public and/or being used to constrain the way one lives or the care one receives (Nat Rev Drug Discov 1:300-308, Issa 2002). That said, to the degree that personalized medicine does become possible, pharmacogenomics and epigenetics will play significant roles in drug development and use.     

Drug-induced hyperglycaemia and diabetes: pharmacogenomics perspectives

Drug-induced diabetes is widely reported in clinical conditions, and it is becoming a global issue because of its potential to increase the risk of severe cardiovascular complications. However, which drug mechanisms exert their diabetogenic effects and why the effects present significant inter-individual differences remain largely unknown. Pharmacogenomics, which is the study of how genomic variation influences drug responses, provides an explanation for individual differences in drug-induced diabetes. We highlight that pharmacogenomics can be involved in regulating the expression of genes in signaling pathways related to the pharmacokinetics or pharmacodynamics of drugs or the pathogenesis of diabetes, contributing to the differences in drug-induced glucose impairment. The pharmacogenomics studies of the major diabetogenic drugs are reviewed, including calcineurin inhibitors, antipsychotics, hormones, and antihypertensive drugs. We intend to elucidate the genetic basis of drug-induced diabetes and pave the way for the precise use of these drugs in the clinic.     

Pharmacogenomics: way to individual therapy

Problems pertaining to the development of individual therapy based on the achievements of modern pharmacogenetics and pharmacogenomics, as well as the safety of using drugs from various pharmacological groups in patients belonging to different ethnical groups (with the corresponding features of metabolism) are considered. The terms "pharmacogenetics" and "pharmacogenomics" are discussed in connection to the significance of genetic polymorphism (or single nucleotide polymorphism) in determining of the individual sensitivity with respect to certain drugs.     

Assessing the cost-effectiveness of pharmacogenomics

The use of pharmacogenomics to individualize drug therapy offers the potential to improve drug effectiveness, reduce adverse side effects, and provide cost-effective pharmaceutical care. However, the combinations of disease, drug, and genetic test characteristics that will provide clinically useful and economically feasible therapeutic interventions have not been clearly elucidated. The purpose of this paper was to develop a framework for evaluating the potential cost-effectiveness of pharmacogenomic strategies that will help scientists better understand the strategic implications of their research assist in the design of clinical trials, and provide a guide for health care providers making reimbursement decisions. We reviewed concepts of cost-effectiveness analysis and pharmacogenomics and identified 5 primary characteristics that will enhance the cost-effectiveness of pharmacogenomics: 1) there are severe clinical or economic consequence that are avoided through the use of pharmacogenomics, 2) monitoring drug response using current methods is difficult, 3) a well-established association between genotype and clinical phenotype exists, 4) there is a rapid and relatively inexpensive genetic test, and 5) the variant gene is relatively common. We use this framework to evaluate several examples of pharmacogenomics. We found that pharmacogenomics offers great potential to improve patients' health in a cost-effective manner. However, pharmacogenomics will not be applied to all currently marketed drugs, and careful evaluations are needed on a case-by-case basis before investing resources in research and development of pharmacogenomic-based therapeutics and making reimbursement decisions.     

顺铂及顺铂载体的研究进展

本文探讨抗肿瘤药顺铂的临床特点及其研究进展,为临床应用提供参考.通过查阅国内外相关文献,系统地了解抗肿瘤药顺铂的临床作用,剂量限制性毒性及耐药性,并检索未获批准及正在进行临床研究的顺铂载体,以分析其临床发展趋势.在过去的10年间,药物研发转向注重药物运输靶向介质,这些新型载体在保留传统顺铂的活性的同时,在很大程度上减少...