治疗药物监测的现状与应用进展

综述治疗药物监测（TDM）的药物种类和常用技术方法,阐述TDM的临床应用现状及所遇到的困难,展望TDM的发展前景。     

浅谈医院开展治疗药物监测的临床意义

目的:通过对治疗药物监测(TDM)的内容、我国现状的简介和临床意义的阐述,加深临床对TDM的了解,提高认识。方法参阅各种文献报导,全面阐述了医院开展TDM的临床意义。结果显示开展TDM对指导临床合理用药,提供个体化给药方案,避免药物不良反应等具有重大意义。结论医院应重视TDM工作,尽快建立和发展治疗药物监测工作,为临床提供更优质的服务。     

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。     

治疗药物监测与临床安全用药

治疗药物监测(TDM)的目的是促进药物个体化治疗。本文通过多年的TDM实践,总结了药物剂量-血药浓度-疗效和不良反应之间的相关性,并重点举例说明TDM对各种常用药物安全应用的重要性,呼吁临床检验师、药师和医师的密切合作,运用多学科知识将TDM推向更高水平,使药物不良反应得到早期警示,以提高药物治疗的有效性和安全性。     

治疗药物监测

<正>治疗药物监测(therapeutic drug monitoring, TDM)是近代临床药物治疗学重大进展之一。目前 TDM已发展成为专门的学科,有关治疗药物监测的杂志、专著和论文逐年增多。国际治疗药物监测和临床毒理学会每两年都要召开一次国际会议,2005 年4月将在美国召开第9届大会。药物监测的范围     

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.     

氨基糖苷类和糖肽类抗菌药物的治疗药物监测

抗菌药物治疗药物监测(TDM)是抗菌药物合理应用必不可少的一部分。氨基糖苷类和糖肽类抗菌药物的药代动力学特点亦决定其TDM的必要性,本文对其进行综述。     

7种药物有效血药浓度参考范围的探讨

目的:探讨7种药物的有效血药浓度参考范围。方法:通过咨询已经开展治疗药物监测(TDM)医院的工作人员,查询药品说明书,出版的书籍及检索相关文献,分析能够达到药物治疗目的的最低有效浓度和出现中毒反应的最小中毒浓度,作为临床TDM值的参考范围。结果:初步确定了万古霉素、卡马西平、丙戊酸钠、地高辛、环孢素、他克莫司和吗替麦考酚酯TDM监测指标及其参考范围。结论:药物TDM监测指标参考值可以为临床药师提供参考,给临床医师个体化用药提供了药物调整剂量的依据,确保药物疗效。     

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。     

神经精神药理学治疗药物监测共识指南:2017版

治疗药物监测(Therapeutic Drug Monitoring,TDM)通过定量测定和解释血药浓度以优化药物治疗.TDM着眼于药代动力学的个体差异,使个体化药物治疗成为可能.在精神病学和神经病学领域中,有可能明显获益于TDM的主要患者群体包括少年儿童、孕妇、老年患者、智障患者、药物滥用者、涉法精神病患者、已知或怀...     

2010～2012年度治疗药物监测室间质评结果分析

目的分析2010～2012年度治疗药物监测（TDM）项目室间质评结果,为提高TDM检测质量提供依据。方法收集2010～2012年参加卫生部临床检验中心全血TDM室间质评的3次结果和血清TDM室间质评医院的6次调查结果,对结果进行统计分析。结果全国开展全血TDM室间质评的医院数从2010年88家增加至2012年102家,开展血清TDM室间质评的医院数从2010年119家增加至2012年136家。全血TDM中,环孢霉素A、他克莫司、西罗莫司的3年平均合格率分别为94．2％、83．4％、89．1％。血清TDM中,茶碱、地高辛、苯妥英、丙戊酸、卡马西平的3年平均合格率分别为94．3％、81．9％、95．4％、96．7％、95．9％。参加实验室的所有方法中,偏振荧光免疫法的应用逐年减少,吖啶酯直接化学发光法和酶增强免疫分析法的应用逐年增加。在3年195个批号的室间质评中,约92．3％批次的方法间变异系数小于20％;7．2％批次方法间变异系数在20％～30％之间;0．5％批次的方法间变异系数大于30％。结论我国TDM室间质评检测质量尚有待提高,应加强TDM的质量控制,推动TDM检测结果的准确、可比,为临床提供可靠的诊疗依据。     

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.     

以治疗药物监测为基础的临床药学实践

目的：介绍以治疗药物监测为基础的临床药学实践方法及体会。方法：从血药浓度的准确测定、知识准备、结果解释的方法和案例分析来加以介绍。结果：药师开展结果解释,可以发现许多影响血药浓度的不良因素,得到医生和病人的认同。结论：系统地开展血药浓度结果解释工作是药师从事临床药学实践的重要内容之一。     

The development of a drug measurement service at St. Paul's Hospital: a pharmacy perspective

Recently, there has been much emphasis on the value of "Therapeutic Drug Monitoring" (TDM). TDM includes clinical attention to the appropriateness, efficacy, side effects and toxicity of drug usage as it relates to the pharmacokinetics of the drug in the patient. The goal of TDM is to optimize drug therapy in each patient through the appropriate choice, dose and monitoring of drug use. The Drug Measurement Service (DMS) at St. Paul's Hospital is a cooperative venture of the departments of medicine, laboratories and pharmacy. The main function of the DMS is TDM. Also, the service educates staff physicians, residents and interns in the proper use and interpretation of serum drug levels. This will make future drug level measurements more beneficial to the patient. This paper outlines the need for a TDM service, the structure and activities of the service, the materials and methods used, and the basic pharmacokinetics and dosing recommendations of the first drug monitored (theophylline). The results of the first six months' experience are presented and discussed.     

Therapeutic drug monitoring for patients with HIV infection: Children's National Medical Center, Washington DC experience

This paper provides a brief overview of therapeutic drug monitoring (TDM) in patients with HIV infection. The manuscipt not only focuses on an update on TDM in HIV infection but also provides the latest information on tandem mass spectrometric methods for antiretroviral drug quantification. Also discussed are the preliminary new and original data on free antiretroviral drug measurement in both plasma and saliva.     

几种药物血药浓度测定的室间质量评价

本文对18个治疗药物监测实验室进行了两次室间质控研究,从而为评价各种测定方法和各实验室测定结果的可靠性和可比性提供了有效的资料和依据。以测定结果的误差百分率在±10%以内为合格标准,89份测定结果中总合格率为66.29%。实验表明:进行治疗药物监测的质量控制是非常必要的。     

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。     

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.     

Poor reliability of therapeutic drug monitoring data for haloperidol and bromperidol using enzyme immunoassay

Therapeutic drug monitoring (TDM) services for plasma concentrations of haloperidol and bromperidol using enzyme immunoassay (EIA) methods are available in Japan, whereas high-performance liquid chromatographic (HPLC) methods are preferred in other countries. To compare these methods, we took 54 plasma samples for haloperidol and 91 plasma samples for bromperidol from schizophrenic patients receiving haloperidol or bromperidol, and the samples were measured using both commercial EIA and HPLC methods. Significant linear correlations were found between the two methods in determining haloperidol (EIA = 1.351 x HPLC + 1.39; r = 0.934, P < 0.001) and bromperidol (EIA = 1.420 x HPLC + 0.712; r = 0.956, P < 0.001) concentrations, but plasma concentrations using the EIA kits were approximately 92% (95% CI; 53-131%) and 62% (54-70%) higher than those using HPLC for haloperidol and bromperidol, respectively. Mean (and range) plasma concentrations of reduced metabolites were 54% (30-92%) and 55% (29-111%) of those of haloperidol and bromperidol, respectively. The present study suggests that reduced metabolites are included to a considerable degree in TDM data using the EIA kits. Therefore, some limitation of TDM data of haloperidol and bromperidol using the EIA kits, ie, high precision but poor accuracy, should be kept in mind.     

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.