药物微生物组在新药研发中的应用

药物基因组学研究宿主基因层面对药物安全性与有效性的作用,指导新药研发过程。但宿主基因层面不能完全解释个体间药效差异。药物微生物组学是药物基因组学的重要扩展,研究肠道微生物对药物安全性与有效性的影响。目前与肠道微生物相关的大数据、多组学分析、粪菌移植、合成生物学等学科与技术已逐步在新药研发中应用,本文综述了新药研发的现状以及肠道微生物与药物相互作用,概括了目前肠道微生物相关药物的研发进展。     

药物基因组学与个体化用药

药物基因组学是研究基因多态性与药物作用的多样性之间的关系的一门新兴学科,药物基因组学可以改善病人用药,提高用药的安全性和有效性,减少药物不良反应的发生,为个体化用药提供理论依据。本文介绍了药物基因组学的概念、研究内容和方法及其在临床个体化用药中的应用及意义。     

药物毒理学研究新技术与新方法

药物研发成功与否主要取决于药物是否安全和有效。综观整个药物研发流程,毒性是终止药物研发的重要原因之一。伴随科学技术的发展,大量新方法、新技术涌入到新药研发中,促使药物毒理学研究得到巨大发展,研究思路也发生了根本性的改变,药物毒理学研究贯穿于新药发现阶段、临床前安全性评价和上市后监督与跟踪的整个过程中,形成了全程式新药安全性研究评价新模式。     

药物基因组学在临床试验中的应用

随着药物基因组学的发展,其在新药研发中逐渐被应用。新药研发是一个高投入、高风险、长周期的过程,药物基因组学在药物靶点的发现、临床前研究、临床研究以及新药上市后不良反应监测方面有重要作用。在Ⅰ～Ⅳ期临床试验中,根据基因型对受试者进行分层分析,可以减少受试者纳入人数,尽可能地减少毒性反应,节省高昂的临床研究成本,缩短上市所需时间。但是,药物基因组学在临床试验中的应用尚处于早期阶段,还面临着许多问题,随着各种新技术的研究和应用,药物基因组学在新药研发上将有更为广阔的前景。     

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。     

FDA对药品说明书中药物基因组学资料的要求

美国食品药品监督管理局（FDA）于2013年1月发布了《临床药物基因组学指导原则：早期临床研究的上市前评价和对说明书的建议》,该指导原则旨在为制药工业界和其他从事新药研发的人在评价人体基因组的变异（尤其是DNA序列变异）如何影响药物的药动学（PK）、药效学（PD）、有效性或安全性方面提供帮助。介绍该指导原则的第五部分“药品说明书中包括的药物基因组学资料”内容,并列举了FDA公布的3个说明书实例,以期对我国药品说明书的撰写和监管工作的开展提供有益的借鉴,以便指导医生和患者合理用药。     

药物毒理学研究中体外替代试验研究现状及展望

药物的安全性和有效性是药物研发成功的决定因素,而药物毒性是终止药物研发的关键因素之一。相关监管指南和指导原则为利用动物进行毒理学研究及生物测试或其他相关试验制定了基本标准。动物体外替代试验不仅遵守了国际上提倡的“3R原则”,也符合毒理学学科发展、社会经济发展及新药研发的要求。动物体外替代试验已成为21世纪毒性测试的重要方向,毒性测试的重点将集中在敏感性终点的选择与评价、细胞-反应网络、高通量与中通量筛选方法的构建及应用、作用机制及作用模式、毒性通路以及系统生物学效应等方面,并且已获得药物研发领域广泛的支持和监管部门的认可,具有广阔的发展前景和重要的应用价值。     

生理药代动力学模型及其在药物相互作用研究中的应用

生理药代动力学模型(PBPK model)在毒理学和药理学领域得到越来越多的关注和应用,如用于药物-药物相互作用(DDI)等研究.DDI会影响药物的安全性、有效性、药物标识及选择药物联用的合理性,其在药物研发和上市后研究中已成为临床药理研究的重要组成部分.基于模型的分析方法被证明是评价DDI作用的有力工具.本文对PBPK模型的特征及其在DDI研究中的应用现状进行阐述.     

第二代抗精神病药物展望

第二代抗精神病药物以其有效性和安全性已广泛应用于临床,本文主要就其药理学机制、各药物的临床优缺点及今后的药物研发方向进行综述。     

药物基因组学及其在合理用药中的应用

药物基因组学 (ｐｈａｒｍａｃｏｇｃｎｏｍｉｃｓ)是 2 0世纪 90年代末发展起来的基于功能基因组学 (ｆｕｎｃｔｉｏｎａｌｇｅｎｏｍｉｃｓ)与分子药理学的一门科学。它从基因水平研究基因序列的多态性与药物效应多样性之间的关系 ,即 :研究基因本身及其突变体对不同个体药物作用效应差异的影响 ,以此为平台开发药物 ,指导合理用药 ,提高用药的安全性和有效性 ,避免不良反应 ,减少药物治疗的费用和风险[1,2 ] 。1　药物基因组学的研究内容与方法药物基因组学是基于药物反应的遗传多态性提出来的 ,遗传多态性是药物基因组学的基础。药物遗…     

Preparing for the revolution--pharmacogenomics and the clinical lab

Pharmacogenomics seeks to apply the field of genomics to improve the efficacy and safety of therapeutics. Sinmply put, pharmacogenomics is genetic-based testing to determine patient therapy. Interestingly, the clinical lab has rarely been discussed within the context of pharmacogenomics. Since clinical labs fill a key role in drug development it is important that they are included in pharmacogenomic discussions. Currently, clinical labs assist pharmaceutical sponsors in preclinical pharmacogenetic testing. In the future, clinical labs will be looked to for genetic test development and validation, and high-throughput genotyping of patients in clinical trials and routine testing. Clinical labs are an essential link in the chain of pharmacogenomic drug development, a fact which must be recognised by both the labs themselves and the industry as a whole.     

Relevance of pharmacogenomics for developing countries in Europe

Pharmacogenomics holds promise of personalized treatment for patients suffering from many common diseases, particularly those with multiple treatment modalities. Owing to recent advances in the deciphering of the human genome sequence, high throughput genotyping technology has led to the reduction of the overall costs of genetic testing and allowed the inclusion of genotype-related dosing recommendations into drug package inserts, hence enabling the integration of pharmacogenomics into clinical practice. Although pharmacogenomics gradually assumes an important part in routine clinical practice in developed countries, many countries, particularly from the developing world, still do not have access either to the knowledge or the resources to individualize drug therapy. The PharmacoGenetics for Every Nation Initiative (PGENI) aims to fill this gap, by making pharmacogenomics globally applicable, not only by defining population-specific pharmacogenomic marker frequency profiles but also by formulating country-specific recommendations for drug efficacy and safety. This article aims to highlight the PGENI activities in Europe in an effort to make pharmacogenomics readily applicable in the European healthcare systems, particularly those in developing countries.     

药物基因组学与个性化药物设计研究进展

药物基因组学是采用基因组学的信息和研究方法，通过分析DNA的遗传变异和监测基因表达谱，以阐明药物反应差异的遗传学本质。这不仅有利于根据药物代谢和药物反应的遗传学特点指导合理用药，而且有利于开发和设计新的药物。综述药物基因组学研究进展，论述与药物开发和临床用药相关的药物代谢的基因组学原理，给出CYP450、药物转运蛋白等实例，概述药物基因组学的一些潜在的用途，预测药物基因组学的发展和临床应用前景。     

CuraGen Corporation

CuraGen Scientists have developed a deep preclinical pipeline of potential protein, antibody and small molecule therapeutics by integrating expertise in molecular biology with a proprietary suite of functional genomic technologies. One important application of functional genomics is in the area of pharmacogenomics, which has been a critical component in CuraGen's drug discovery and development efforts. By identifying safety and efficacy issues early in the discovery process and by gaining a better understanding of a drug's mechanism of action, CuraGen scientists are able to make more informed decisions about which drugs are the most appropriate to advance through the preclinical and clinical development stages.     

Pharmacogenomics of acetylsalicylic acid and other nonsteroidal anti-inflammatory agents: clinical implications

Purpose

Pharmacogenomics investigates interindividual genetic variability in the DNA sequence of drug targets, drug-metabolizing enzymes or disease genes, RNA expression, or protein translation of genes affecting drug response and drug safety. Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications with well-documented variation in patient response in terms of efficacy and safety. This variation may in part be explained by pharmacogenomics.

Methods

In this paper I review data on the pharmacogenomics of aspirin and other NSAIDs focusing on clinical implications.

Results

Existing scientific evidence supports the pharmacogenomic basis of interindividual variation in treatment response to aspirin and NSAIDs, with clinical implications for antiplatelet action, cancer chemoprevention, and drug safety. However, further research efforts are needed before knowledge on the pharmacogenomics of aspirin and NSAIDs can be implemented in clinical practice.

Conclusion

The outcome of these research efforts would be anticipated to have added value for both science and society, contributing to the enhanced efficacy and safety of these agents through patient selection.     

Pharmacogenomics and personalized medicine: a review focused on their application in the Chinese population

The field of pharmacogenomics was initiated in the 1950s and began to thrive after the completion of the human genome project 10 years ago. Thus far, more than 100 drug labels and clinical guidelines referring to pharmacogenomic biomarkers have been published, and several key pharmacogenomic markers for either drug safety or efficacy have been identified and subsequently adopted in clinical practice as pre-treatment genetic tests. However, a tremendous variation of genetic backgrounds exists between different ethnic groups. The application of pharmacogenomics in the Chinese population is still a long way off, since the published guidelines issued by the organizations such as US Food and Drug Administration require further confirmation in the Chinese population. This review highlights important pharmacogenomic discoveries in the Chinese population and compares the Chinese population with other nations regarding the pharmacogenomics of five most commonly used drugs, ie, tacrolimus, cyclosporine A, warfarin, cyclophosphamide and azathioprine.     

Pharmacogenomics – how close/far are we to practising individualized medicine for children?

The translation of pharmacogenomics into clinical practice is a key approach for practising individualized medicine, which aims to maximize drug efficacy and minimize drug toxicity. Since the completion of both the Human Genome Project and the International HapMap project, the development of pharmacogenomics has been greatly facilitated. However, progress in translating pharmacogenomics into clinical practice, especially in paediatric medicine, is unexpectedly slow. Many challenges from different areas remain. This paper discusses the existing applications and the limitations to the implementation of paediatric pharmacogenomics, as well as possible solutions for overcoming these limitations and challenges.     

Pharmacogenomics: bench to bedside

Pharmacogenetics is the study of the role of inheritance in inter-individual variation in drug response. Since its origins in the mid-twentieth century, a major driving force in pharmacogenetics research has been the promise of individualized drug therapy to maximize drug efficacy and minimize drug toxicity. In recent years, the convergence of advances in pharmacogenetics with rapid developments in human genomics has resulted in the evolution of pharmacogenetics into pharmacogenomics, and led to increasing enthusiasm for the 'translation' of this evolving discipline into clinical practice. Here, we briefly summarize the development of pharmacogenetics and pharmacogenomics, and then discuss the key factors that have had an influence on - and will continue to affect - the translation of pharmacogenomics from the research bench to the bedside, highlighting the challenges that need to be addressed to achieve this goal.     

Pharmacogenomics: the influence of genomic variation on drug response

Unpredictable efficacy and toxicity are major hurdles in the administration of many medications. By identifying inherited DNA polymorphisms that influence drug disposition and effects, pharmacogenomics is an exciting tool for the individualization of drug therapies. Single nucleotide polymorphisms (SNP) in genes encoding drug metabolizing enzymes, drug transporters, and DNA repair genes have recently been shown to influence drug toxicity and efficacy. This review will discuss clinically relevant examples of genetic polymorphisms that influence the outcome of drug therapy, and possibilities for future applications of pharmacogenomics.