治疗药物监测概况及研究进展

通过查阅有关书籍和近年国内外的文献资料,回顾治疗药物监测(TDM)的发展与现状,介绍目前进行TDM的药物种类和常用技术方法,展望遗传药理学在个体化用药中的应用前景。未来的治疗药物监测模式是传统模式和药物遗传学监测相结合,进一步完善个体给药方案的制定。     

治疗药物监测概况及研究进展

通过查阅有关书籍和近年国内外的文献资料,回顾治疗药物监测(TDM)的发展与现状,介绍目前进行TDM的药物种类和常用技术方法,展望遗传药理学在个体化用药中的应用前景.未来的治疗药物监测模式是传统模式和药物遗传学监测相结合,进一步完善个体给药方案的制定.     

我院十五年治疗药物监测临床实践的回顾性分析

目的:总结我院治疗药物监测工作的经验,为中小型医院开展治疗药物监测工作提供参考思路。方法:汇总分析我院1998-2012年治疗药物监测的品种、方法学及监测数量的变化情况。结果:我院治疗药物监测工作经历了三个不同的发展阶段,监测方法学不断完善,监测数量逐步增加,治疗药物监测工作对促进临床合理用药发挥了较大作用。结论:认识治疗药物监测工作对提高临床治疗水平的价值,结合各单位实际情况来配备仪器设备和培养专业技术人员,按照"监测方法因地制宜、监测品种逐步增加、监测数量由少到多、监测方式循序渐进"的发展思路,治疗药物监测工作也一定能在中小型医院蓬勃开展。     

对治疗药物监测工作的思考和建议

治疗药物监测(TDM)在我国的发展已经有近30年,监测的技术、方法、药物类别等已有很大发展,其为临床治疗提供的价值也逐渐被认可。为契合近年来的医疗改革精神,推动TDM工作进一步发展,为临床治疗提供更多的支持与帮助,在总结TDM工作已有成绩和经验的基础上,有以下的思考和建议。     

治疗药物监测的概念探析

治疗药物监测主要是通过实现临床药物治疗个体化,提高药物的临床有效性和安全性。在我国,治疗药物监测工作开展已经历30余年的历程,可查阅有关治疗药物监测的概念,其表述却不尽相同,各有侧重点。而一个学科概念或定义对该学科发展至关重要。为了促进治疗药物监测发展,本文查阅国内外有关治疗药物监测相关的历史文献,总结其发展过程,以期为规范治疗药物监测概念提供参考。     

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。     

以实例探讨临床药学的发展方向

目的：探讨临床药学的发展方向。方法：通过回顾医院药学的发展历程,分析我国临床药学发展的现状,列举具体实例,论证临床药师在促进医院合理用药方面发挥的作用。结果：临床药师通过参与临床药物治疗、开展治疗药物监测、实施药品不良反应监测、提供用药咨询服务及建立静脉药物配制中心,促进了治疗药物的合理应用,减少了不良反应的发生。结论：全程化药学服务是临床药学发展的方向。     

治疗药物监测的方法学研究进展

治疗药物监测(TDM)指的是在转向药学技术服务,保障患者使用药物安全的前提之下逐渐发展起来。在临床当中,因为人体差异以及其他相关因素,患者通过相同途径采取相同剂量药物以后,临床治疗反应却是存在较大差异。治疗药物监测就是利用定量分析生物样本当中的药物以及代谢产物浓度,正确指导临床使用药物,进而保证使用药物具有安全有效性。群体药动学方法是将药动学参数与疗效联系在一起,有利于正确指导个体化治疗,是治疗药物监测的主要工具。LC-MS在TDM工作当中的作用日趋重要。有限采样法通过有限点的血药浓度值对药物暴露量给予准确估算,进而使TDM更加经济适应,可以在临床当中广泛应用,同时方法学研究的不断进步对TDM的工作发展起到良好的促进作用。     

临床药物个体化治疗技术体系研究进展

临床药物个体化治疗是精准医疗的重要组成部分,代表现代医学的最新发展趋势,旨在保障患者用药安全、有效和经济.近年来随着分子生物学、基因组学和生物信息学技术的进步,临床药物个体化治疗已开始利用药物基因组学、治疗药物监测等技术获得一些良好的治疗效果,新兴的类器官技术也在肿瘤药物治疗领域崭露头角.综述临床药物个体化治疗技术体系...     

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。     

Recent advances in analytical methods for the therapeutic drug monitoring of immunosuppressive drugs

Therapeutic drug monitoring (TDM) of immunosuppressive drugs (ISDs) with a narrow therapeutic index is an increasingly popular tool for minimizing drug toxicity while maximizing the prevention of graft loss and organ rejection. This review focuses on trends regarding analytical methods for the TDM of ISDs since 2011. The five most commonly prescribed immunosuppressive medications are critically reviewed: cyclosporine A, tacrolimus, sirolimus (rapamycin), everolimus, and mycophenolic acid. This review introduces the general background of TDM and ISDs and presents the recent developments in using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and immunoassays for the TDM of ISDs. Finally, a future perspective for these analytical methods is briefly discussed.     

我院2001～2006年抗癫痫药血药浓度监测数据分析

目的:阐述治疗药物监测(TDM)对抗癫痫药合理应用的意义,关注临床科室对TDM的认识程度。方法:建立抗癫痫药Access数据库,对我院2001～2006年抗癫痫药TDM结果进行分析。结果:我院抗癫痫药监测例数逐年上升;由监测结果计算的抗癫痫药有效浓度、高血药浓度、低血药浓度比例显示血药浓度监测极有必要,但患者的个体用药信息缺乏限制了抗癫痫药个体化用药的发展。结论:TDM虽应用日益广泛,但仍需医师、药师共同努力,以最大限度地保证抗癫痫药的个体化应用。     

精神药物的治疗药物监测

目的:对精神药物的治疗药物监测(TDM)现状进行了总结分析,以指导临床合理用药。方法:结合国内外相关文献,从TDM的历史、临床意义、测定方法、药物与TDM的关系、成本效益分析等方面进行了评价。结果:一些精神药物如氟哌啶醇、氟奋乃静、碳酸锂、多塞平、米帕明、地昔帕明、去甲替林、氯氮平的药效关系及治疗窗已经确定,临床中应进行TDM。奥氮平和利培酮在临床中推荐使用TDM。结论:精神药物的TDM对临床有积极的意义,但临床实施尚有待加强,随着药动学-药效学等的发展,更多的精神药物的TDM将被证实。     

Clinical utility of drug measurement and pharmacokinetics – therapeutic drug monitoring in psychiatry

Based on the assumption that a relationship between blood levels and clinical effects (therapeutic effects, adverse events and toxicity) can be defined and considering that after equal doses plasma concentrations vary markedly between individual patients, therapeutic drug monitoring (TDM) can assist to personalize dose adjustment. Taken together, drug levels and a knowledge of the pharmacological profile of the administered drugs can enable the optimal dosage to be tailored according to the need of the individual patient. Therapeutic drug monitoring has been established for a limited number of drugs. In psychiatry, it has a 40-year-long history, which started with nortriptyline. Evidence has accumulated which shows that TDM is a valid tool for the optimization of psychopharmacotherapy. When used adequately, TDM is helpful for many patients and in many situations. Combined with pharmacogenetic tests, the metabolic status of a patient can be well characterized. Several new observations have been made during routine TDM that have stimulated clinical pharmacological research, such as investigations on inherited differences in drug metabolism that are closely linked to TDM in psychiatry. The contributions of individual forms of cytochrome P450 (CYP) to the metabolism of drugs was elicited by clinical observations on pharmacokinetic drug interactions. Therapeutic drug monitoring requires a close collaboration between the prescribing physician, the laboratory specialist, the clinical pharmacologist and the patient. This complexity may result in errors which can be detected by analysing the appropriate use of TDM in clinical practice. More education has to be provided to the prescribing clinicians on the pharmacology of the drugs and the algorithm of TDM. Moreover, clinical trials should include measurements of blood concentrations during drug development to generate valid data on the relationships between drug concentrations and clinical outcomes under well-controlled conditions. This would merely increase the amount of work and costs, as high-throughput methods are now available in many laboratories. Any progress in TDM has direct benefits for the treatment of many individual patients.     

Therapeutic drug monitoring in the management of HIV-infected patients

The rate of HIV-positive patients that fails to reach or to maintain a durable virological suppression under anti-retroviral (ARV) therapy might be as high as 50%, therefore new tools to improve ARV drug efficacy are urgently needed. Among others, therapeutic drug monitoring (TDM) is a strategy by which the dosing regimen for a patient is guided by measurement of plasma drug levels, enabling physicians to optimize ARV drug efficacy and to avoid drug-related toxicity. The most used analytical methods to determine plasma levels of ARV drugs are HPLC-UV and HPLC-MS(/MS), recently MALDI-based methods and enzyme immunoassay (EIA) technologies have been also employed. The wide inter-patient variability in ARV drug pharmacokinetic supports the application of TDM to the clinical management of HIV-infected patients. Drug-drug and drug-food interactions, drug binding to plasma proteins, drug sequestering by erythrocytes, hepatic impairment, sex, age, pregnancy, and host genetic factors are sources of inter-patient variability affecting ARV drug pharmacokinetics. Combining the information of TDM and resistance tests in genotypic inhibitory quotient (GIQ) is likely to be of great clinical utility. Indeed, only two clinical trials on GIQ, both conducted using ARV drugs not more commonly in use, have shown clinical benefits. The design of new trials with long follow-up and sample size representative of the current HIV prevalence is urgently needed to give indications for GIQ as an early predictor of virological response. Here, the basic principles and the available methods for TDM in the management of HIV-infected patients are reviewed.     

Therapeutic drug monitoring in Turkey: experiences from Istanbul

Therapeutic drug monitoring (TDM) has assumed an important place in patient management in the last few decades. In this study, serum drug levels determined in 7759 specimens sent to the Department of Pharmacology and Clinical Pharmacology in 1994 and 1998 for TDM were retrospectively evaluated. Monitored drugs were carbamazepine, valproate, phenytoin, phenobarbital, digoxin, theophylline, and salicylate. The comparison of the results obtained for the relevant 2 years showed that there was a remarkable increase in the number of requests for TDM per year and in the rate of serum drug levels that were within therapeutic range. Serum antiepileptic drug level monitoring accounted for a major part of the data. Overall data suggest that the use of TDM in antiepileptic drugs is improving; conversely, digoxin and theophylline are still not being properly monitored. In this study, the results are discussed in the light of rational TDM criteria.     

Cost-effectiveness of therapeutic drug monitoring: a systematic review

There are a number of effective but highly toxic drugs that exhibit a narrow therapeutic index and marked interpatient pharmacokinetic variability. Individualized therapy with such drugs requires therapeutic drug monitoring (TDM) to obtain the desired clinical effects safely. Cost-effectiveness analysis in health care is still at an early stage of development, especially for TDM. A systematic review was carried out to document studies that have addressed the cost-effectiveness of TDM. The Cochrane database and Medline were searched. References identified by this approach were then searched manually for relevant articles. Very few studies have been performed that document the cost-effectiveness of TDM, and TDM has been demonstrated to be cost-effective only for aminoglycosides. For the other classes of drugs that are monitored, the rationale for TDM has been supported, but appropriate cost-effectiveness analyses have not been performed. Because the use of many of these drugs without TDM would increase the risk of under- or overdosing, emphasis should not be placed solely on cost-effectiveness but rather on how such interventions can be applied in the most cost-effective and clinically useful manner.     

Therapeutic drug monitoring in cancer chemotherapy

For a select number of drugs, proper management of patients includes monitoring serum or plasma concentrations of the drugs and adjusting the doses accordingly - this practice is referred to as therapeutic drug monitoring (TDM). The need for TDM arises when pharmacokinetic variability of drugs is not easily accounted for by common clinical parameters. Many chemotherapeutic drugs have large interindividual variability, yet TDM is not commonplace in chemotherapy management. This review will discuss pharmacokinetics in the context of chemotherapeutic drugs, examine the few instances where TDM is currently used in the field of oncology and propose other drugs where TDM might be useful for dose adjustments in the management of chemotherapy.     

危重患者ECMO生命支持期间抗真菌药物TDM与剂量调整

目的： 分析危重患者体外膜肺氧合（ECMO）生命支持期间治疗药物监测（TDM）的意义,提供抗真菌药物剂量调整方案。方法： 检索PubMed、Cochrane Library至今有关ECMO期间抗真菌药物TDM相关文献进行分析综述。结果： ECMO对伏立康唑、泊沙康唑、艾沙康唑、两性霉素B脂质体的药动学影响明显,TDM结果显示,ECMO支持期间药物暴露明显降低,需要增加剂量以达到预期临床效果,推荐依据TDM结果进行个体化药物治疗方案调整;氟康唑、阿尼芬净、两性霉素B脱氧胆酸盐受ECMO影响小,可使用常规剂量并进行必要的TDM;TDM有助于提高抗真菌治疗的成功率。结论： ECMO支持期间抗真菌药物的药动学呈现复杂变化,推荐进行TDM并依次调整临床药物治疗方案。     

治疗药物监测临床应用现状

回顾治疗药物监测(TDM)的临床应用等,本文重点综述抗癫痫药物与免疫抑制药物的TDM临床应用评价,分析开展TDM过程中存在的问题。