体内药物分析技术在临床药学工作中的应用进展

目的 探讨体内药物分析技术在临床药学工作中的应用进展。方法 查阅相关文献,对临床样本的特点、临床常用的体内药物分析方法、体内药物分析在临床药学中的应用以及现存的问题进行综述。结果和结论 近年来,随着临床个体化治疗、精准治疗的需求增大,以及分析技术的不断发展,体内药物分析技术广泛地应用于临床药学工作中,成为促进临床合理用药、提高个体化治疗水平、减少药品不良反应发生的重要辅助技术之一。但在实际应用中,还存在血液采样的侵入性阻碍采样、药物监测结果解释能力弱和临床检测方法等仍有待完善的问题。这些问题应当引起重视,并在后续的研究和应用中不断改善和解决。     

浅谈临床药学在医药间的"桥梁"作用

治疗药物监测(TDM)是以药动学、药效学的基本理论为指导,借助先进在体内药物分析技术和数据处理方法,研究药物在体内变化规律的一项科学技术性较强的工作。它     

我国体内药物分析文献中药物的系统评价

近年来,我国在临床药理学、药代动力学、生物药剂学、药物不良反应监测及临床药物监测等方面迅速发展,而上述研究都以体内药物及代谢物的浓度测定为基础,体内药物浓度测定技术已形成一门新兴学科--生物药物分析(biopharmaceutical analysis),即体内药物分析[1～2].     

高原环境影响治疗监测药物代谢的研究进展

高原环境会影响药物在体内的代谢，使得药动学参数、药物代谢酶及转运体的表达及功能均会发生变化。随着医药行业的快速发展，治疗药物监测（TDM）作为个体化用药的依据被广泛的关注，高原环境对监测药物有何影响?笔者通过查阅国内外相关文献，对临床上常用的治疗监测药物种类、治疗窗以及检测血样进行了归纳和总结，分析高原低氧环境对临床常用监测药物代谢的影响。为高原临床治疗药物监测提供参考，更好的保证高原人群合理用药，也为后期课题组开展高原治疗药物监测以及研究药物的遴选提供参考。     

药物基因毒性杂质及其检测方法研究现状

基因毒性杂质（GTI）主要来源于原料药的合成过程或储藏运输等环节，其在痕量水平即可造成DNA损伤并诱发细胞癌变，因此近年来受到了广泛关注。各国法规对不同种类的GTI均提出了严格的限量标准和控制策略，因此发展灵敏可靠的检测方法应用于原料药中GTI的筛查、定量及表征具有重要意义。本文介绍了药物中GTI的警示结构及其分类、常见来源和毒理学限量标准，重点结合国内外研究进展对气相色谱及其联用技术、液相色谱及其联用技术、电化学传感和表面增强拉曼光谱等新型技术应用于药物GTI的检测进行评述，并探讨基于警示结构或生物效应导向的通量筛查策略和方法，以期为药物GTI的有效监测研究提供参考。     

共用注射器是增加爱滋病发生率的因素之一

治疗药物监测(Therapeutic Drug Monitoring,简称TDM)是最近十年来临床治疗学中发展较为迅速领域之一。对于某些治疗剂量范围较窄的药物,通过对病人血液或其他体液中药物浓度的监测,随时掌握药物在体内的变化,可使临床用药更趋于合理化和个体化,借以避免或减少药物的不良反应,从而达到安全治疗的目的。 TDM的理论基础是临床药理学、药效学和药物动力学。通过血药浓度监测为确定给药方案、选择最佳剂量、时间间隔和预测药物的累积毒性提供依据。进行此项工作必须有灵敏和精确的监测方法,因为血液内药物浓度往往很低,一般化学方法不易测出。目前较多应用色谱法,但技术要求较高,需专人掌握,而免疫学方法测定血内药物浓度有现成试剂盒,一般临床实验室较易掌握,为普及推广TDM工作创造了条件。本文对免疫分析法中常用的放射免疫分析、酶免疫分析、荧光免疫分析等方法作了全面介绍,可供参考。TDM工作必须有临床药师、临床医师、临床药理医师、临床检验师等共同参加,密切配合及协作,才能推广开展,进一步提高临床药物治疗的水平。     

计算机在治疗药物监测中的软件开发与应用

目的：利用计算机对治疗药物监测资料进行现代化管理。方法：根据治疗药物监测的一般流程,运用数据库程序设计技术编制应用软件。结果与结论：本软件可用于治疗药物监测的日常工作,由此建立的数据库可用于数据统计及临床资料查询、分析,值得在医院推广应用。     

传感器技术在体内药物分析中的应用概述

对生物体内肉眼无法观测到的生物活性物质以及药物的分布和代谢进行连续监测,一直是医学家、药理学家和生理学家们研究的目标。传统的体内药物分析方法仅限于色谱法及其与质谱、核磁共振等方法的联用,由于这些方法均需要繁杂的前处理如抽取动物体液后经一系列纯化过程或先处死动物,在组织匀浆后采用复杂的检测设备进行离体检测分析,因此,成本高、耗时长、对机体损害大、不便于进行在体连续监测等。这些缺点使这些方法的应用受到极大的限制。传感器技术可用于在体分析的微型     

治疗药物监测进展

目的 :阐述治疗药物监测的必要性和测定技术。方法 :对所监测的药物、取样和分析方法进行综述。结果 :说明了药物监测的范围和指标 ,样品需求的条件 ,重点比较了色谱技术和免疫分析法在TDM中的应用和各自的优越性。结论 :确保TDM的顺利进行 ,必须具备临床知识和掌握分析技术。     

治疗药物监测的研究进展

本文从临床开展治疗药物监测药物种类的变化、分析监测方法技术和交叉学科的发展等多个方面阐述了近年来治疗药物监测学科的研究进展。液质联用和免疫检测法是临床常用方法,准确、快速、经济的检测方法是未来技术发展的重点,药物基因组学、游离药物浓度监测技术和群体药动学（PPK）将成为未来治疗药物监测领域重要的发展方向。     

Advances in biopharmaceutical analysis in the People's Republic of China: 1991–1993

The methodological studies on biopharmaceutical analysis of drugs and their metabolites by liquid and gas chromatography with various detectors have been reviewed. Research articles were selected from well known journals published in the People's Republic of China between January 1991 and March 1993. The applications of these methods in bioavailability, pharmacokinetics, therapeutic drug monitoring and metabolic studies have also been discussed.     

Pharmaceutical biotechnology products approved within the European Union.

The manufacture of therapeutic proteins represented the first true industrial application of recombinant DNA technology. Thus far some 88 recombinant proteins/monoclonal antibody-based products have gained marketing approval within the European Union (EU). This represents 36% of all new drug approvals since the introduction of the new centralized European drug approval system in 1995. More recently, an increasing proportion of approved proteins are engineered, tailored to display altered pharmacokinetic profiles or reduced immunogenicity in man. Currently no nucleic acid-based products are approved in the EU. Technical innovations/milestones likely characterizing the biopharmaceutical industry within the next decade include approval of some products produced in transgenic systems, approval of some products administered by non-parenteral means, approval of at least some nucleic acid-based products and the identification of novel biopharmaceuticals/biopharmaceutical targets through discoveries in functional genomics and proteomics.     

免疫分析方法在体内药物分析中的应用(英文)

免疫分析方法十分灵敏,而又具有很好的特异性。当常规的药物分析方法在样本前处理或是检测环节遇到困难时,免疫分析方法常可提供解决办法,尤其是在涉及到生物样本的前处理或生物药物浓度检测时更为重要。本文对免疫分析方法在体内药物分析中的应用进行了综述,包括生物样本前处理时的免疫萃取与免疫耗竭,以及目标药物测试过程中的各种常用的及新的免疫分析方法。     

Particles in Biopharmaceutical Formulations,Part 2: An Update on Analytical Techniques and Applications for Therapeutic Proteins,Viruses, Vaccines and Cells

Particles in biopharmaceutical formulations remain a hot topic in drug product development. With new product classes emerging it is crucial to discriminate particulate active pharmaceutical ingredients from particulate impurities. Technical improvements, new analytical developments and emerging tools (e.g., machine learning tools) increase the amount of information generated for particles. For a proper interpretation and judgment of the generated data a thorough understanding of the measurement principle, suitable application fields and potential limitations and pitfalls is required. Our review provides a comprehensive overview of novel particle analysis techniques emerging in the last decade for particulate impurities in therapeutic protein formulations (protein-related, excipient-related and primary packaging material-related), as well as particulate biopharmaceutical formulations (virus particles, virus-like particles, lipid nanoparticles and cell-based medicinal products). In addition, we review the literature on applications, describe specific analytical approaches and illustrate advantages and drawbacks of currently available techniques for particulate biopharmaceutical formulations.     

Role of analytical ultracentrifugation in assessing the aggregation of protein biopharmaceuticals

In developing and manufacturing protein biopharmaceuticals, aggregation is a parameter that needs careful monitoring to ensure the quality and consistency of the final biopharmaceutical drug product. The analytical method of choice used to perform this task is size-exclusion chromatography (SEC). However, it is becoming more and more apparent that considerable care is required in assessing the accuracy of SEC data. One old analytical tool that is now reappearing to help in this assessment is analytical ultracentrifugation (AUC). Developments in AUC hardware and, more importantly, recent developments in AUC data analysis computer programs have converged to provide this old biophysical tool with the ability to extract very high resolution size information about the molecules in a given sample from a simple sedimentation velocity experiment. In addition, AUC allows sample testing to be conducted in the exact or nearly exact liquid formulation or reconstituted liquid formulation of the biopharmaceutical in the vial, with minimal surface area contact with extraneous materials. As a result, AUC analysis can provide detailed information on the aggregation of a biopharmaceutical, while avoiding many of the major problems that can plague SEC, thus allowing AUC to be used as an orthogonal method to verify SEC aggregation information and the associating properties of biopharmaceuticals.     

Biopharmaceutical challenges associated with drugs with low aqueous solubility--the potential impact of lipid-based formulations

The percentage of new chemical entities synthesised with low aqueous solubility and high therapeutic efficacy is growing, this presents major challenges for the drug delivery scientists. The role of physicochemical properties in identification of suitable drug candidates for oral lipid-based delivery systems is discussed. A knowledge of the interplay of physicochemical and biopharmaceutical drug properties with the physiological environment of the gastro-intestinal tract (GIT), as a prerequisite to successful formulation design, is reviewed. The importance of excipient selection with an emphasis on bioactive excipients is stressed. The need for more examples of in vitro-in vivo correlations as a means of maximizing the development potential and commercial future for lipid-based formulations, and, promoting confidence within the industry for these delivery systems is highlighted.     

中国霉酚酸治疗药物监测的现状分析

目的 分析国内霉酚酸治疗药物监测(TDM)的开展现状.方法 检索EmBase、PubMed、Cochrane图书馆、中国知网、万方数据库及中国生物医学文献数据库,检索时限均为建库至2019年3月.纳入接受霉酚酸治疗并进行血药浓度监测的中国患者的原始研究,统计纳入文献的基本特征、给药方案、采样时间、采样方法及检测指标等信...     

基于“先进合同研究组织”的生物医药产业创新模式探讨

目的:探索我国的生物医药产业创新模式。方法:分析我国生物医药产业的核心——新药研发中存在的研发基地建设薄弱、资金不足、成果转化难三大问题,基于"合同研究组织(CRO)"建立产业创新模式。结果:提出由"多并发CRO"的研发模式、风险投资与专利/新药证书对接的融资形式以及新药证书为导向的研发过程管理组成的产业创新模式,并整合为"先进合同研究组织(CRO+)"。结论:该模式是一种开放性集成服务体系,有利于缩短生物医药研发周期,降低研发成本与研发风险,促进我国生物医药产业发展。     

Therapeutic success via targeted approaches and strategic partnerships with clinical laboratories

The future of personalized medicine and the biopharmaceutical industry may lie in the close interaction between drug developers and clinical laboratories. The output of the Human Genome Project and other basic research into various diseases is generating data on individual variation in the treatment responses of patients; the biopharmaceutical industry and clinical laboratories will be expected to use this information to identify those patients who are best able to respond to a particular targeted therapy. Strategic partnerships between drug companies and clinical laboratories will be the centerpiece of this new era of medical treatment, providing higher-resolution diagnostics as well as more efficacious and safer treatment options.     

Application of bioaffinity mass spectrometry for analysis of ligands

Bioaffinity mass spectrometry is a novel technology for analysis of binding proteins and their ligands. In this review, we introduce the concepts and principles of bioaffinity surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS). Various preactivated chip types and several approaches for binding of ligands or their binders to the chips are discussed. We also provide specific examples for the use of this technology for screening antibodies, analyzing ligands, glycoconjugates, protein-protein inter-actions, and DNA (RNA) binding proteins. In pursuit of developing new tests or studies of mechanism of drug action in therapeutic drug monitoring practice, this technology may provide a more rapid approach for ligand-binder studies.