抗肿瘤药物的治疗监测

大多数抗肿瘤药具有治疗指数低、毒性大、药动学参数个体差异大的特性 ,临床需进行治疗药物监测 ,以达到个体化给药。但治疗药物监测最基本的条件———量效关系 ,对大多数肿瘤药而言只是量毒关系 ,基于提高临床疗效的治疗药物监测除少数药物外目前尚不可行     

我院抗癫痫类药物血药浓度监测回顾性分析

目的：了解抗癫痫药物血药浓监测结果对临床用药的指导意义及用药合理性,方法：对我院1994－1999年主要抗癫痫药卡西平等血药浓度监测结果及临床疗效进行分析,评价,结果：抗癫痫治疗指数低,有效剂量个体差异大,血药浓度监测对调整给药剂量有指导意义,结论：应用视血药浓度监测,以保证临床治疗效果,减少不良反应。     

1990～2003年我院治疗药物监测结果回顾分析

目的分析治疗药物监测结果,为临床合理用药提供参考.方法对1990～2003年315例应用抗癫痫药苯妥英、卡马西平、苯巴比妥,平喘药氨茶碱,镇静催眠药硝西泮、氯硝西泮、艾司唑仑、地西泮、劳拉西泮、三唑仑,抗精神失常药氯氮平,抗焦虑药多塞平以及地高辛、阿司匹林等患者血药浓度监测结果进行回顾分析.结果监测药物的个体差异大,药物相互作用复杂,容易出现药物中毒.结论治疗药物监测对临床合理用药具有重要意义,为临床开展个体化给药以及急性药物中毒的诊断、治疗等提供参考.     

伏立康唑的药动学/药效学及其药物监测

伏立康唑为新一代三唑类抗真菌药,抗菌谱广,抗菌作用强,主要用于治疗患有进展性、可能威胁生命的真菌感染的患者。其药动学呈非线性,个体差异大。本文对伏立康唑药动学影响因素,药动学/药效学特性,血药浓度与治疗效果、不良反应间关系以及不同类患者伏立康唑药物监测作一综述,以指导临床制定个性化给药方案,提高药物治疗效果。     

精神神经系药物的监测及临床参考

精神神经系药物的监测及临床参考钟明康，王宏图，张静华（上海医科大学华山医院２０００４０）目前大多数药物经药动学或临床经验进行给药方案设计，获得了满意疗效。但对异常代谢者，如心、肝、肾功能异常，或过度肥胖、年幼或年迈，或联合用药，或依从性差等，其实际浓...     

开展治疗药物监测的体会

通过建立病人药历，全面了解病人的用药情况和病情，再有的放矢地开展治疗药物监测，解决药物治疗中的不合理现象，以期达到安全用药，有效用药的目的，本文根据本院建立药历，开展治疗药物监测的情况，谈了作者的体会，供临床药师参考。     

抗肿瘤药的HPLC体内测定

抗肿瘤药的治疗指数低，毒副反应严重。为研究时间药理学在治疗中的作用，充分发挥药物的治疗作用与降低药物的不良反应，必须了解药物体内的吸收、分布过程。近年来，随着治疗药监测和时辰化疗的兴起，大量文献报告了抗肿瘤的测定方法，并用于体内药物代谢与药代动力学的研究，对指导临床合理用药起着推动作用。高效液相色谱法(HPLC)由于灵敏度高，对各种代谢产物分离效果好，操作简便，已成为临床最主要的测定方法。本文主要对临床常用的抗肿瘤药的体内HLPC测定方法作一综述，为临床测定提供参考。     

群体药动学应用于个体化给药的研究进展

群体药动学运用经典的药动学原理结合统计学方法,以稀疏数据预测患者血药浓度,可达到监测药物体内过程和指导临床个性化给药的目的。查阅近年来的相关文献,结合实例综述群体药动学应用于治疗窗窄的药物、个体差异大的药物、联合用药、特殊人群用药等方面的最新进展,为其深入研究和指导临床用药提供参考。     

高原低氧环境影响抗癫痫药物的研究进展

高原低氧环境通过改变机体胃肠排空速率、器官血流量、药物血浆蛋白结合率、药物代谢酶和转运体表达等影响药物的药代谢动力学过程。癫痫是一种需长期用药的脑部疾病,而大多数抗癫痫药物的治疗指数低、有效血药浓度范围窄。临床上常用治疗药物监测(therapeutic drug monitoring,TDM)来寻找抗癫痫药物的最佳个体化用药方法。该文对临床上常用抗癫痫药及其治疗窗进行归纳总结,并分析高原低氧环境对抗癫痫药物药代动力学的影响,为高原抗癫痫药物临床用药提供参考。     

耐多药结核病和严重耐多药结核病治疗进展

20世纪末以来,由于耐药菌株的产生和治疗的不合理等多种原因,耐多药结核病和严重耐多药结核病的发生率不断升高,使得结核病重新成为临床治疗的大问题。大多数情况下,只要合理选择和联用现有的抗结核药物,耐多药结核病和严重耐多药结核病是可以治愈的。本文总结临床常用的一些抗结核药物在治疗耐多药结核病和严重耐多药结核病时推荐的用法和治疗方案,以及为避免长期使用抗生素所致二重感染的中药治疗方法。同时在制定治疗方案时应充分考虑药敏试验结果、长期用药的安全性和有效性,联合用药的原则,进行规律、全程的治疗,就可减少耐多药结核病和严重耐多药结核病的病死率。     

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。     

治疗药物监测数据管理系统的开发与应用

目的:建立治疗药物监测(TDM)数据管理系统,实现对患者血药浓度和随行质控数据的信息化管理。方法:在Windows平台下利用Access数据库技术,通过建立各表之间的关系、创建查询、报表设计、创建窗体、建立各窗体之间的联系、切换面板设计管理等开发了TDM数据管理系统。结果与结论:建立的系统用户界面良好,数据类型多样、录入便捷,各表数据之间可实现级联更新,数据检索便捷,可进行报表打印及有效、规范的数据管理与统计分析,并实现随行质控数据的及时跟踪与管理,服务于临床与患者。     

1812例/次环孢素治疗药物监测结果分析

目的:评价1812例/次环孢素治疗药物监测和临床用药情况。方法:对我院502例患者1812次符合入选条件的环孢素监测结果进行统计分析。结果:首次治疗药物监测结果在有效治疗窗内的仅占41.4%;治疗药物监测次数为1、2、3次者分别占总人数的44.8%、16.3%、11.6%;在所有监测次数为3次～4次的患者中,第1、2、3、4次治疗药物监测结果在治疗窗内的分别占总人数的40.6%、48.0%、50.0%、57.9%。结论:治疗药物监测虽然广泛应用,但监测次数偏少;即使监测多次,达标情况仍不理想,应高度重视这种不能很好调整患者用药的现象;同时,这与药费昂贵等因素有关。     

住院特殊人群和需进行治疗药物监测的药品不良反应报告分析

目的:了解我院住院特殊人群和需进行治疗药物监测(TDM)的药品不良反应(ADR)分布,促进临床合理用药。方法:对我院2005-2011年临床各科室呈报的ADR病例,按照国家ADR监测中心制定的标准进行描述、因果关系分析评价、分级汇总及统计分析。结果:2159例ADR报告中男性1146例(53.07%),女性1013例(46.93%);在需进行TDM的药物中,引起ADR比率最高的为抗癫痫类药物(60.77%);ADR病例数随着肝功能和肾功能损害的加重而增加。结论:我院住院特殊人群和需进行TDM的药物的ADR较多,应合理使用药物,并对ADR予以关注。     

Target concentration intervention in oncology: where are we at?

Therapeutic drug monitoring (TDM) and more recently target concentration intervention (TCI) have been widely used in clinical practice for the optimization of drug treatment. TDM and TCI have been applied most frequently in the cardiovascular, respiratory, neurology, and infectious disease areas because the medications used here have both narrow therapeutic indices and a clear relationship between concentration and effect. However, apart from drugs such as methotrexate and 5-fluorouracil, the clinical application of TDM/TCI in oncology is minimal. An important reason for this is that a therapeutic index for most anticancer agents has not been established. However, in the last 20 years, relationships between plasma drug concentrations and clinical outcome have been defined for various chemotherapeutic agents. Defining concentration-effect relationships is also complicated by the fact that cancer is almost always treated with multiple drugs given in combination making the precise definition of the pharmacodynamics of individual agents difficult. The increase in patients with obesity and also those underweight adds to the complexity of effective oncology treatment. This review describes some of the evidence that supports the use of TDM/TCI in oncology. It is proposed that as more patients previously ineligible for chemotherapy become eligible, TDM/TCI may play a critical role in optimizing chemotherapy outcomes. However, pharmacokinetic-pharmacodynamic research to investigate both therapeutic benefit and feasibility in daily clinical practice is required.     

Therapeutic Drug Monitoring of Golimumab in the Treatment of Ulcerative Colitis

Ulcerative colitis (UC) is a relapsing-remitting chronic inflammatory disorder affecting the mucosal surface in a continuous manner from the rectum through part of, or the entire, colon. Patients with severe disease and those who become refractory or intolerant to corticosteroids and/or immunosuppressants, require treatment with biologic agents that target tumor necrosis factor-α (TNF). Golimumab, a fully human monoclonal antibody, is the latest TNF antagonist to get approved for the treatment of moderate-to-severe UC. Subcutaneously administered golimumab induces and maintains clinical response, remission, and mucosal healing. Serum concentrations of golimumab are associated with response to therapy, as patients with higher drug exposure are more likely to achieve these outcomes. Since various patient and disease-related factors were shown to influence the pharmacokinetics of TNF antagonists, drug exposure may be variable over time and between patients, affecting success of therapy. A major contributing factor is immunogenicity, with development of anti-drug antibodies (ADAb) and an accelerated clearance of drug as a result. Although there is a growing body of evidence to support therapeutic drug monitoring (TDM) for infliximab and adalimumab, two other TNF antagonists, only limited data is available for golimumab. In addition, the clinically important drug exposure thresholds are not widely known, which has limited the use of TDM for golimumab in clinical practice. This review summarizes available data regarding the use of golimumab for UC, with emphasis on the pharmacokinetics, exposure-response relationship, and the role of TDM in optimizing therapy.     

儿童抗癫痫药物治疗药物监测

抗癫痫药物（AEDs）是治疗癫痫的主要药物,现有27种抗癫痫药物,这使得治疗药物监测（TDM）的应用越来越广泛,同时,抗癫痫药物也是进行TDM最常见的药物。第一代抗癫痫药物卡马西平、苯巴比妥、苯妥英钠、乙琥胺、扑米酮、丙戊酸在TDM方面积累了很多经验,现在TDM将更多地应用于新的抗癫痫药物如醋酸艾司利卡西平、非氨酯、加巴喷丁、拉科酰胺、拉莫三嗪、左乙拉西坦、奥卡西平、吡仑帕奈、哌拉西坦、普瑞巴林、瑞替加滨、卢非酰胺、司替戊醇、噻加宾、托吡酯、氨己烯酸和唑尼沙胺。本文通过对样本类型、样本的采集和处理、参考范围的概念进行综述,旨在为儿童抗癫痫用药的药物监测提供依据。     

Development of an individualized therapy for establishing the optimal dosage by the pharmacokinetics profiles of anticancer agents

Therapeutic drug monitoring (TDM) is widely applied to a variety of medications, including antibiotics, immunosuppressants, and antidepressants, but the clinical utility of TDM for anticancer agents is currently limited by several factors. The primary reason is the poorly-defined concentration-effect relationships for most anticancer drugs. TDM has the potential to improve the clinical use of anticancer agents. This paper reviews the relations between the pharmacokinetics of a new anticancer agent, amrubicin, and the clinical response and toxic side effects in patients. The plasma concentration of amrubicin peaked immediately after a bolus intravenous injection of the drug and declined in a biexponential manner thereafter, whereas that of C-13 hydroxy metabolite amrubicinol also peaked just after amrubicin injection but decreased more gradually compared with that of amrubicin. The apparent total clearance of amrubicin showed a large interindividual variability, despite adjustment of dosage for body surface area. Leukocytopenia of grades 3 or 4 occurred in most patients, and thrombocytopenia and anemia of grades 3 or 4 were also common. Since the area-under the curves of amrubicin and amrubicinol seemed to be associated with the severity of hematological toxicities, it is thought that the plasma concentration of amrubicin and amrubicinol may provide useful information for establishing the optimal dosage of amrubicin in each patient.     

1073人次丙戊酸治疗药物监测结果分析

目的:分析1 073人次丙戊酸药物浓度监测的数据,并评价治疗药物监测的临床意义.方法:对我院604例患者1 073人次符合入选条件的丙戊酸监测数据进行分析、统计.结果:首次治疗药物监测(TDM)结果在有效治疗窗内的仅占40.7%;TDM次数为1次、2次和3次的分别占总人数的70.86%、16.06%和4.47%;在所有测定3次或4次的患者中,第1次、2次、3次和第4次TDM结果在治疗窗内的分别占总人数的4.55%、20.45%、54.55%和35.29%.结论:TDM虽然广泛应用,但是由于多种原因导致监测次数偏少,监测结果达标情况不理想,需要引起临床的高度重视.